Recording Gamma Band Oscillations in Pedunculopontine Nucleus Neurons.

PubMed

Urbano, Francisco J; Luster, Brennon R; D'Onofrio, Stasia; Mahaffey, Susan; Garcia-Rill, Edgar

2016-09-14

Synaptic efferents from the PPN are known to modulate the neuronal activity of several intralaminar thalamic regions (e.g., the centrolateral/parafascicular; Cl/Pf nucleus). The activation of either the PPN or Cl/Pf nuclei in vivo has been described to induce the arousal of the animal and an increment in gamma band activity in the cortical electroencephalogram (EEG). The cellular mechanisms for the generation of gamma band oscillations in Reticular Activating System (RAS) neurons are the same as those found to generate gamma band oscillations in other brains nuclei. During current-clamp recordings of PPN neurons (from parasagittal slices from 9 - 25 day-old rats), the use of depolarizing square steps rapidly activated voltage-dependent potassium channels that prevented PPN neurons from being depolarized beyond -25 mV. Injecting 1 - 2 sec long depolarizing current ramps gradually depolarized PPN membrane potential resting values towards 0 mV. However, injecting depolarizing square pulses generated gamma-band oscillations of membrane potential that showed to be smaller in amplitude compared to the oscillations generated by ramps. All experiments were performed in the presence of voltage-gated sodium channels and fast synaptic receptors blockers. It has been shown that the activation of high-threshold voltage-dependent calcium channels underlie gamma-band oscillatory activity in PPN neurons. Specific methodological and pharmacological interventions are described here, providing the necessary tools to induce and sustain PPN subthreshold gamma band oscillation in vitro.

Use-dependent inhibition of Na+ currents by benzocaine homologs.

PubMed Central

Quan, C; Mok, W M; Wang, G K

1996-01-01

Most local anesthetics (LAs) elicit use-dependent inhibition of Na+ currents when excitable membranes are stimulated repetitively. One exception to this rule is benzocaine, a neutral LA that fails to produce appreciable use-dependent inhibition. In this study, we have examined the use-dependent phenomenon of three benzocaine homologs: ethyl 4-diethylaminobenzoate, ethyl 4-ethoxybenzoate, and ethyl 4-hydroxybenzoate. Ethyl 4-hydroxybenzoate at 1 mM, like benzocaine, elicited little use-dependent inhibition of Na+ currents, whereas ethyl 4-diethylaminobenzoate at 0.15 mM and ethyl 4-ethoxybenzoate at 0.5 mM elicited substantial use-dependent inhibition--up to 55% of peak Na+ currents were inhibited by repetitive depolarizations at 5 Hz. Each of these compounds produced significant tonic block of Na+ currents at rest and shifted the steady-state inactivation curve (h infinity) toward the hyperpolarizing direction. Kinetic analyses showed that the decaying phase of Na+ currents during a depolarizing pulse was significantly accelerated by all drugs, thus suggesting that these drugs also block the activated channel. The recovery time course for the use-dependent inhibition of Na+ currents was relatively slow, with time constants of 6.8 and 4.4 s for ethyl 4-diethylaminobenzoate and ethyl 4-ethoxybenzoate, respectively. We conclude that benzocaine and 4-hydroxybenzoate interact with the open and inactivated channels during repetitive pulses, but during the interpulse the complex dissociates too fast to accumulate sufficient use-dependent block of Na+ currents. In contrast, ethyl 4-diethylaminobenzoate and ethyl 4-ethoxybenzoate dissociate slowly from their binding site and consequently elicit significant use-dependent block. A common LA binding site suffices to explain the presence and absence of use-dependent block by benzocaine homologs during repetitive pulses. PMID:8770198

Membrane currents underlying activity in frog sinus venosus

PubMed Central

Brown, Hilary F.; Giles, Wayne; Noble, Susan J.

1977-01-01

1. The spontaneous electrical activity of small strips of muscle from the sinus venosus region of the heart of Rana catesbeiana was investigated using the double sucrose gap technique. The voltage clamp was used to record the ionic currents underlying the pace-maker depolarization and the action potential. 2. The records of spontaneous electrical activity are very similar to those obtained from the sinus venosus using micro-electrodes. Moreover, the pace-maker activity is almost completely insensitive to tetrodotoxin (TTX) at 2·0 × 10-6 g/ml., which suggests that the pace-maker responses can be classified as primary, as opposed to follower pacing. 3. In response to short rectangular depolarizing voltage clamp pulses, only one inward current is activated. This current is almost completely insensitive to TTX but can be blocked by manganese ions. It appears, therefore, to be equivalent to the slow inward (Ca2+/Na+) current, Isi, of other cardiac tissues. The threshold for Isi is near to the maximum diastolic potential, indicating that it must be activated during the pace-maker depolarization. 4. Interruption of the normal pace-maker depolarization by rapid activation of the voltage clamp circuit reveals the time-dependent decay of outward current. This current reverses between -75 and -90 mV and, therefore, is probably carried mainly by potassium ions. 5. Outward current decay is not a simple exponential, and Hodgkin—Huxley analysis suggests that two distinct components of outward current may be present. One of these is activated in the potential range of the pace-maker depolarization and the other at more positive potentials. Both outward currents reach full, steady-state activation at about zero mV, i.e. within the `plateau' range of the sinus action potential. 6. These results are compared with other recently published voltage clamp data from the rabbit sino—atrial node. 7. A hypothesis for the generation of pace-maker activity is presented which involves (i) decay of outward current and (ii) activation of the slow inward current, Isi. PMID:303699

Action of certain tropine esters on voltage-clamped lobster axon.

PubMed

Blaustein, M P

1968-03-01

Tropine p-tolylacetate (TPTA) and its quaternary analogue, tropine p-tolylacetate methiodide (TPTA MeI) decrease the early transient (Na) and late (K) currents in the voltage-clamped lobster giant axon. These agents, which block the nerve action potential, reduce the maximum Na and K conductance increases associated with membrane depolarization. They also slow the rate at which the sodium conductance is increased and shift the (normalized) membrane conductance vs. voltage curves in the direction of depolarization along the voltage axis. All these effects are qualitatively similar to those resulting from the action of procaine on the voltage-clamped axon. One unusual effect of the tropine esters, noticeable particularly at large depolarization steps, is that they cause the late, K current to reach a peak and then fall off with increasing pulse duration. This effect has not been reported to occur as a result of procaine action. Tropine p-chlorophenyl acetate (TPClphiA), which differs from TPTA only by the substitution of a p-Cl for a p-CH(3) group on the benzene ring, had a negligible effect on axonal excitability.

Action of Certain Tropine Esters on Voltage-Clamped Lobster Axon

PubMed Central

Blaustein, M. P.

1968-01-01

Tropine p-tolylacetate (TPTA) and its quaternary analogue, tropine p-tolylacetate methiodide (TPTA MeI) decrease the early transient (Na) and late (K) currents in the voltage-clamped lobster giant axon. These agents, which block the nerve action potential, reduce the maximum Na and K conductance increases associated with membrane depolarization. They also slow the rate at which the sodium conductance is increased and shift the (normalized) membrane conductance vs. voltage curves in the direction of depolarization along the voltage axis. All these effects are qualitatively similar to those resulting from the action of procaine on the voltage-clamped axon. One unusual effect of the tropine esters, noticeable particularly at large depolarization steps, is that they cause the late, K current to reach a peak and then fall off with increasing pulse duration. This effect has not been reported to occur as a result of procaine action. Tropine p-chlorophenyl acetate (TPClφA), which differs from TPTA only by the substitution of a p-Cl for a p-CH3 group on the benzene ring, had a negligible effect on axonal excitability. PMID:5648830

Electrical behaviour of myenteric neurones in the gastric corpus of the guinea-pig.

PubMed Central

Schemann, M; Wood, J D

1989-01-01

1. Electrical behaviour of ganglion cells in the myenteric plexus of the guinea-pig stomach was investigated using intracellular recording methods. 2. Three subpopulations were identified and classified for convenience of discussion as gastric I, II and III neurones. Gastric I neurones were characterized by repetitive spike discharge during depolarizing current pulses and by higher input resistance than the other types. Gastric II neurones discharged one or two spikes only at the onset of long-lasting depolarizing current pulses. Gastric III neurones did not discharge spikes to depolarizing current pulses and had higher membrane potentials and lower input resistances than the other types. Non-stimulus evoked discharge ('spontaneous' discharge) did not occur in any of the neurones. 3. Resting membrane potentials were generated primarily by resting K+ conductance, but were smaller than the estimated K+ equilibrium potential. Analysis based on the constant field equation predicted lower K+ conductance in gastric I than in gastric III neurones. 4. Action potentials in gastric I and II neurones were suppressed or blocked by tetrodotoxin. Spikes that were broadened by tetraethylammonium appeared to have an inward component of Ca2+ current. 5. Hyperpolarizing after-potentials were associated with the spikes of both kinds of neurones. These after-potentials had much shorter duration (less than 300 ms) than the post-spike hyperpolarization of AH/type 2 intestinal neurones and unlike intestinal neurones there was no latency between the positive after-potential of the spike and the onset of the hyperpolarization. After-hyperpolarization in the gastric neurones was enhanced when the spikes were broadened by tetraethylammonium and was suppressed by removal of Ca2+ from the bathing solution. 6. Treatment with either tetraethylammonium or 4-aminopyridine enhanced excitability and induced 'spontaneously' occurring repetitive spike discharge. 7. The electrophysiological behaviour of gastric myenteric neurones differed significantly from intestinal neurones. This was interpreted as specialization of the neural networks that control and co-ordinate the activity of vastly different effector systems in the two regions of the alimentary canal. Images Fig. 1 PMID:2621607

Separate Cl^- Conductances Activated by cAMP and Ca2+ in Cl^--Secreting Epithelial Cells

NASA Astrophysics Data System (ADS)

Cliff, William H.; Frizzell, Raymond A.

1990-07-01

We studied the cAMP- and Ca2+-activated secretory Cl^- conductances in the Cl^--secreting colonic epithelial cell line T84 using the whole-cell patch-clamp technique. Cl^- and K^+ currents were measured under voltage clamp. Forskolin or cAMP increased Cl^- current 2-15 times with no change in K^+ current. The current-voltage relation for cAMP-activated Cl^- current was linear from -100 to +100 mV and showed no time-dependent changes in current during voltage pulses. Ca2+ ionophores or increased pipette Ca2+ increased both Cl^- and K^+ currents 2-30 times. The Ca2+-activated Cl^- current was outwardly rectified, activated during depolarizing voltage pulses, and inactivated during hyperpolarizing voltage pulses. Addition of ionophore after forskolin further increased Cl^- conductance 1.5-5 times, and the current took on the time-dependent characteristics of that stimulated by Ca2+. Thus, cAMP and Ca2+ activate Cl^- conductances with different properties, implying that these second messengers activate different Cl^- channels or that they induce different conductive and kinetic states in the same Cl^- channel.

Effect of the depolarization field on coherent optical properties in semiconductor quantum dots

NASA Astrophysics Data System (ADS)

Mitsumori, Yasuyoshi; Watanabe, Shunta; Asakura, Kenta; Seki, Keisuke; Edamatsu, Keiichi; Akahane, Kouichi; Yamamoto, Naokatsu

2018-06-01

We study the photon echo spectrum of self-assembled semiconductor quantum dots using femtosecond light pulses. The spectrum shape changes from a single-peaked to a double-peaked structure as the time delay between the two excitation pulses is increased. The spectrum change is reproduced by numerical calculations, which include the depolarization field induced by the biexciton-exciton transition as well as the conventional local-field effect for the exciton-ground-state transition in a quantum dot. Our findings suggest that various optical transitions in tightly localized systems generate a depolarization field, which renormalizes the resonant frequency with a change in the polarization itself, leading to unique optical properties.

Calcium-sensitive and insensitive transient outward current in rabbit ventricular myocytes.

PubMed Central

Hiraoka, M; Kawano, S

1989-01-01

1. A suction pipette whole-cell voltage-clamp technique was used to record membrane currents and potentials of isolated ventricular myocytes from rabbit hearts. 2. Transient outward current (Ito) was activated by voltage steps positive to -20 mV, increasing in amplitude with further depolarization to reach a maximum around +70 mV. The current attained its peak within 10 ms and then it inactivated for 100-200 ms. 3. A large portion of Ito still remained after the calcium current (ICa) was blocked when depolarizing pulses were applied at a frequency of 0.1 Hz or less. Therefore, this current component is referred to as calcium-insensitive Ito or It. 4. It showed voltage- and time-dependent inactivation similar to that observed in Purkinje fibres and other cardiac preparations. 5. The reversal potential of It depended on external K+ concentration, [K+]o, with a slope of 32 mV per 10-fold change in the presence of a normal [Na+]o (143 mM), while the slope was 48 mV per 10-fold change in low [Na+]o (1.0 mM). 6. It was completely inhibited by 2-4 mM-4-aminopyridine. Ito in the presence of ICa was also partially blocked by 4-aminopyridine and the remainder was abolished by 5 mM-caffeine. 7. The calcium-insensitive and caffeine-sensitive Ito differed in their decay rates as well as in their recovery time courses. The former was predominantly available at a slow pulsing rate, while the latter increased its amplitude with high-frequency depolarization. 8. The caffeine-sensitive Ito was inhibited by a blockade of ICa, by replacing Ca2+ with Sr2+, by external application of ryanodine and by internal application of EGTA. This indicates that the current is calcium-sensitive and is dependent on increased myoplasmic Ca2+ through Ca2+ influx via the sarcolemma and Ca2+ release from the sarcoplasmic reticulum. The current is therefore designated as IK, Ca. 9. The physiological functions of IK, Ca and It are indicated by their contribution to ventricular repolarization at fast and slow heart rates, respectively. PMID:2552080

Characteristics of action potentials and their underlying outward currents in rat taste receptor cells.

PubMed

Chen, Y; Sun, X D; Herness, S

1996-02-01

1. Taste receptor cells produce action potentials as a result of transduction mechanisms that occur when these cells are stimulated with tastants. These action potentials are thought to be key signaling events in relaying information to the central nervous system. We explored the ionic basis of action potentials from dissociated posterior rat taste cells using the patch-clamp recording technique in both voltage-clamp and current-clamp modes. 2. Action potentials were evoked by intracellular injection of depolarizing current pulses from a holding potential of -80 mV. The threshold potential for firing of action potentials was approximately -35 mV; the input resistance of these cells averaged 6.9 G omega. With long depolarizing pulses, two or three action potentials could be elicited with successive attenuation of the spike height. Afterhyperpolarizations were observed often. 3. Both sodium and calcium currents contribute to depolarizing phases of the action potential. Action potentials were blocked completely in the presence of the sodium channel blocker tetrodotoxin. Calcium contributions could be visualized as prolonged calcium plateaus when repolarizing potassium currents were blocked and barium was used as a charge carrier. 4. Outward currents were composed of sustained delayed rectifier current, transient potassium current, and calcium-activated potassium current. Transient and sustained potassium currents activated close to -30 mV and increased monotonically with further depolarization. Up to half the outward current inactivated with decay constants on the order of seconds. Sustained and transient currents displayed steep voltage dependence in conductance and inactivation curves. Half inactivation occurred at -20 +/- 3.1 mV (mean +/- SE) with a decrease of 11.2 +/- 0.5 mV per e-fold. Half maximal conductance occurred at 3.6 +/- 1.8 mV and increased 12.2 +/- 0.6 mV per e-fold. Calcium-activated potassium current was evidenced by application of apamin and the use of calcium-free bathing solution. It was most obvious at more depolarized holding potentials that inactivated much of the transient and sustained outward currents. 5. Potassium currents contribute to both the repolarization and afterhyperpolarization phases of the action potential. These currents were blocked by bath application of tetraethylammonium, which also substantially broadened the action potential. Application of 4-aminopyridine was able to selectively block transient potassium currents without affecting sustained currents. This also broadened the action potential as well as eliminated the afterhyperpolarization. 6. A second type of action potential was observed that differed in duration. These slow action potentials had t1/2 durations of 9.6 ms compared with 1.4 ms for fast action potentials. Input resistances of the two groups were indistinguishable. Approximately one-fourth of the cells eliciting action potentials were of the slow type. 7. Cells eliciting fast action potentials had large outward currents capable of producing a quick repolarization, whereas cells with slow action potentials had small outward currents by comparison. The average values of fast cells were 2,563 pA and 1.4 ms compared with 373 pA and 9.6 ms for slow cells. Current and duration values were related exponentially. No significant difference was noted for inward currents. 8. These results suggest that many taste receptor cells conduct action potentials, which may be classified broadly into two groups on the basis of action potential duration and potassium current magnitude. These groups may be related to cell turnover. The physiological role of action potentials remains to be elucidated but may be important for communication within the taste bud as well as to the afferent nerve.

Effects of tetraethylammonium on potassium currents in a molluscan neurons

PubMed Central

1981-01-01

The effects of tetraethylammonium (TEA) on the delayed K+ current and on the Ca2+-activated K+ current of the Aplysia pacemaker neurons R-15 and L-6 were studied. The delayed outward K+ current was measured in Ca2+-free ASW containing tetrodotoxin (TTX), using brief depolarizing clamp pulses. External TEA blocks the delayed K+ current reversibly in a dose-dependent manner. The experimental results are well fitted with a Michaelis-Menten expression, assuming a one-to-one reaction between TEA and a receptor site, with an apparent dissociation constant of 6.0 mM. The block depends on membrane voltage and is reduced at positive membrane potentials. The Ca2+-activated K+ current was measured in Ca2+- free artificial seawater (ASW) containing TTX, using internal Ca2+ ion injection to directly activate the K+ conductance. External TEA and a number of other quaternary ammonium ions block the Ca2+-activated K+ current reversibly in a dose-dependent manner. TEA is the most effective blocker, with an apparent dissociation constant, for a one-to- one reaction with a receptor site, of 0.4 mM. The block decreases with depolarization. The Ca2+-activated K+ current was also measured after intracellular iontophoretic TEA injection. Internal TEA blocks the Ca2+- activated K+ current (but the block is only apparent at positive membrane potentials), is increased by depolarization, and is irreversible. The effects of external and internal TEA can be seen in measurements of the total outward K+ current at different membrane potentials in normal ASW. PMID:6265594

Molecular Basis of Paralytic Neurotoxin Action on Voltage-Sensitive Sodium Channels

DTIC Science & Technology

1987-10-20

reaching a new steady state rate of inactivation after 5 min. Fig. 6C shows a family of sodium currents elicited by depolarizations to test potentials...Fig. 7 compares time courses of decay of sodium currents during test pulses to +10 mV for 70 msec in the presence or absence of I x 10-7 CsTx on semi...logarithmic coordinates. The decay of the sodium currents in the absence of toxin was described by a single exponential with a decay constant of 0.7

Low K+-induced hyperpolarizations trigger transient depolarizations and action potentials in rabbit ventricular myocytes

PubMed Central

Akuzawa-Tateyama, M; Tateyama, M; Ochi, R

1998-01-01

The effects of large reductions of [K+]o on membrane potential were studied in isolated rabbit ventricular myocytes using the whole-cell patch clamp technique.Decreasing [K+]o from the normal level of 5.4 mm to 0.1 mm increased resting membrane potential (Vrest) from −75.6 ± 0.3 to −140.3 ± 1.9 mV (means ± s.e.m; n = 127), induced irregular, transient depolarizations with mean maximal amplitudes of 19.5 ± 1.5 mV and elicited action potentials in 56.7 % of trials. The action potentials exhibited overshoots of 37.9 ± 1.5 mV (n = 72) and sustained plateaux.Addition of 0.1 mm La3+ in the presence of 0.1 mm[K+]o significantly increased Vrest but decreased the amplitude of transient depolarizations and suppressed the firing of action potentials.Replacement of external Na+ or Cl− with N-methyl-D-glucamine or aspartate, respectively, or internal dialysis with 10 mm EGTA or BAPTA had little effect on low [K+]o-induced membrane potential changes.Hyperpolarizing voltage clamp pulses to potentials between −110 and −200 mV activated irregular inward currents that increased in amplitude and frequency with increasing hyperpolarization and were depressed by 0.1 mm La3+.The generation of transient depolarizations by low [K+]o can be explained as being a consequence of decreasing the inward rectifier K+ current (IK1) and the appearance of inward currents reflecting electroporation resulting from strong electric fields across the membrane. PMID:9824717

Electroporation of DC-3F cells is a dual process.

PubMed

Wegner, Lars H; Frey, Wolfgang; Silve, Aude

2015-04-07

Treatment of biological material by pulsed electric fields is a versatile technique in biotechnology and biomedicine used, for example, in delivering DNA into cells (transfection), ablation of tumors, and food processing. Field exposure is associated with a membrane permeability increase usually ascribed to electroporation, i.e., formation of aqueous membrane pores. Knowledge of the underlying processes at the membrane level is predominantly built on theoretical considerations and molecular dynamics (MD) simulations. However, experimental data needed to monitor these processes with sufficient temporal resolution are scarce. The whole-cell patch-clamp technique was employed to investigate the effect of millisecond pulsed electric fields on DC-3F cells. Cellular membrane permeabilization was monitored by a conductance increase. For the first time, to our knowledge, it could be established experimentally that electroporation consists of two clearly separate processes: a rapid membrane poration (transient electroporation) that occurs while the membrane is depolarized or hyperpolarized to voltages beyond so-called threshold potentials (here, +201 mV and -231 mV, respectively) and is reversible within ∼100 ms after the pulse, and a long-term, or persistent, permeabilization covering the whole voltage range. The latter prevailed after the pulse for at least 40 min, the postpulse time span tested experimentally. With mildly depolarizing or hyperpolarizing pulses just above threshold potentials, the two processes could be separated, since persistent (but not transient) permeabilization required repetitive pulse exposure. Conductance increased stepwise and gradually with depolarizing and hyperpolarizing pulses, respectively. Persistent permeabilization could also be elicited by single depolarizing/hyperpolarizing pulses of very high field strength. Experimental measurements of propidium iodide uptake provided evidence of a real membrane phenomenon, rather than a mere patch-clamp artifact. In short, the response of DC-3F cells to strong pulsed electric fields was separated into a transient electroporation and a persistent permeabilization. The latter dominates postpulse membrane properties but to date has not been addressed by electroporation theory or MD simulations. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Depolarization of Pulsar Radio Emission.

PubMed

Lyutikov

1999-11-01

We show that intensity-dependent depolarization of single pulses may be due to the nonlinear decay of the "upper" ordinary (O) mode into an unpolarized extraordinary mode and a backward-propagating wave. The decay occurs in the innermost parts of the pulsar magnetosphere for obliquely propagating O waves.

Influence of pHo on calcium channel block by amlodipine, a charged dihydropyridine compound. Implications for location of the dihydropyridine receptor

PubMed Central

1989-01-01

We have investigated the modulation of L-type calcium channel currents in isolated ventricular cells by the dihydropyridine derivative amlodipine, a weak base with a pKa of 8.6. Under conditions that favor neutral drug molecules, amlodipine block resembles other, previously described, neutral dihydropyridine derivatives: block is more pronounced at depolarized voltages, repetitive pulsing is not needed to promote block, and recovery is complete at hyperpolarized voltages. When the drug is ionized, depolarized voltages still enhance block, however, the time course is slow and speeded by repetitive pulses that open channels. Recovery from block by ionized drug molecules is very slow and incomplete, but can be rapidly modified by changes in external hydrogen ion concentration. We conclude from these observations that the degree of ionization of the drug molecule can affect access to the dihydropyridine receptor and that external protons can interact with the drug-receptor complex even if channels are blocked and closed. These observations place limitations on the location of this receptor in the ventricular cell membrane. PMID:2549176

Mechanism of orientation of stimulating currents in magnetic brain stimulation (abstract)

NASA Astrophysics Data System (ADS)

Ueno, S.; Matsuda, T.

1991-04-01

We made a functional map of the human motor cortex related to the hand and foot areas by stimulating the human brain with a focused magnetic pulse. We observed that each functional area in the cortex has an optimum direction for which stimulating currents can produce neural excitation. The present report focuses on the mechanism which is responsible for producing this anisotropic response to brain stimulation. We first obtained a functional map of the brain related to the left ADM (abductor digiti minimi muscles). When the stimulating currents were aligned in the direction from the left to the right hemisphere, clear EMG (electromyographic) responses were obtained only from the left ADM to magnetic stimulation of both hemisphere. When the stimulating currents were aligned in the direction from the right to the left hemisphere, clear EMG signals were obtained only from the right ADM to magnetic stimulation of both hemisphere. The functional maps of the brain were sensitive to changes in the direction of the stimulating currents. To explain the phenomena obtained in the experiments, we developed a model of neural excitation elicited by magnetic stimulation. When eddy currents which are induced by pulsed magnetic fields flow in the direction from soma to the distal part of neural fiber, depolarized area in the distal part are excited, and the membrane excitation propagates along the nerve fiber. In contrast, when the induced currents flow in the direction from the distal part to soma, hyperpolarized parts block or inhibit neural excitation even if the depolarized parts near the soma can be excited. The model explains our observation that the orientation of the induced current vectors reflect both the functional and anatomical organization of the neural fibers in the brain.

Transient compartment-like syndrome and normokalaemic periodic paralysis due to a Cav1.1 mutation

PubMed Central

Fan, Chunxiang; Lehmann-Horn, Frank; Weber, Marc-André; Bednarz, Marcin; Groome, James R.; Jonsson, Malin K. B.

2013-01-01

We studied a two-generation family presenting with conditions that included progressive permanent weakness, myopathic myopathy, exercise-induced contracture before normokalaemic periodic paralysis or, if localized to the tibial anterior muscle group, transient compartment-like syndrome (painful acute oedema with neuronal compression and drop foot). 23Na and 1H magnetic resonance imaging displayed myoplasmic sodium overload, and oedema. We identified a novel familial Cav1.1 calcium channel mutation, R1242G, localized to the third positive charge of the domain IV voltage sensor. Functional expression of R1242G in the muscular dysgenesis mouse cell line GLT revealed a 28% reduced central pore inward current and a −20 mV shift of the steady-state inactivation curve. Both changes may be at least partially explained by an outward omega (gating pore) current at positive potentials. Moreover, this outward omega current of 27.5 nS/nF may cause the reduction of the overshoot by 13 mV and slowing of the upstroke of action potentials by 36% that are associated with muscle hypoexcitability (permanent weakness and myopathic myopathy). In addition to the outward omega current, we identified an inward omega pore current of 95 nS/nF at negative membrane potentials after long depolarizing pulses that shifts the R1242G residue above the omega pore constriction. A simulation reveals that the inward current might depolarize the fibre sufficiently to trigger calcium release in the absence of an action potential and therefore cause an electrically silent depolarization-induced muscle contracture. Additionally, evidence of the inward current can be found in 23Na magnetic resonance imaging-detected sodium accumulation and 1H magnetic resonance imaging-detected oedema. We hypothesize that the episodes are normokalaemic because of depolarization-induced compensatory outward potassium flux through both delayed rectifiers and omega pore. We conclude that the position of the R1242G residue before elicitation of the omega current is decisive for its conductance: if the residue is located below the gating pore as in the resting state then outward currents are observed; if the residue is above the gating pore because of depolarization, as in the inactivated state, then inward currents are observed. This study shows for the first time that functional characterization of omega pore currents is possible using a cultured cell line expressing mutant Cav1.1 channels. Likewise, it is the first calcium channel mutation for complicated normokalaemic periodic paralysis. PMID:24240197

Sub-threshold depolarizing pre-pulses can enhance the efficiency of biphasic stimuli in transcutaneous neuromuscular electrical stimulation.

PubMed

Vargas Luna, Jose Luis; Mayr, Winfried; Cortés-Ramirez, Jorge-Armando

2018-06-09

There is multiple evidence in the literature that a sub-threshold pre-pulse, delivered immediately prior to an electrical stimulation pulse, can alter the activation threshold of nerve fibers and motor unit recruitment characteristics. So far, previously published works combined monophasic stimuli with sub-threshold depolarizing pre-pulses (DPPs) with inconsistent findings-in some studies, the DPPs decreased the activation threshold, while in others it was increased. This work aimed to evaluate the effect of DPPs during biphasic transcutaneous electrical stimulation and to study the possible mechanism underlying those differences. Sub-threshold DPPs between 0.5 and 15 ms immediately followed by biphasic or monophasic pulses were administered to the tibial nerve; the electrophysiological muscular responses (motor-wave, M-wave) were monitored via electromyogram (EMG) recording from the soleus muscle. The data show that, under the specific studied conditions, DPPs tend to lower the threshold for nerve fiber activation rather than elevating it. DPPs with the same polarity as the leading phase of biphasic stimuli are more effective to increase the sensitivity. This work assesses for the first time the effect of DPPs on biphasic pulses, which are required to achieve charge-balanced stimulation, and it provides guidance on the effect of polarity and intensity to take full advantage of this feature. Graphical abstract In this work, the effect of sub-threshold depolarizing pre-pulses (DPP) is investigated in a setup with transcutaneous electrical stimulation. We found that, within the tested 0-15 ms DPP duration range, the DPPs administered immediately before biphasic pulses proportionally increase the nerve excitability as visible in the M-waves recorded from the soleus muscle. Interestingly, these findings oppose published results, where DPPs, administered immediately before monophasic stimuli via implanted electrodes, led to decrease of nerve excitability.

Ab Initio Calculations of Ultrashort Carrier Dynamics in Two-Dimensional Materials: Valley Depolarization in Single-Layer WSe2

NASA Astrophysics Data System (ADS)

Molina-Sánchez, Alejandro; Sangalli, Davide; Wirtz, Ludger; Marini, Andrea

2017-08-01

In single-layer WSe$_2$, a paradigmatic semiconducting transition metal dichalcogenide, a circularly polarized laser field can selectively excite electronic transitions in one of the inequivalent $K^{\\pm}$ valleys. Such selective valley population corresponds to a pseudospin polarization. This can be used as a degree of freedom in a valleytronic device provided that the time scale for its depolarization is sufficiently large. Yet, the mechanism behind the valley depolarization still remains heavily debated. Recent time-dependent Kerr experiments have provided an accurate way to visualize the valley dynamics by measuring the rotation of a linearly polarized probe pulse applied after a circularly polarized pump pulse. We present here a clear, accurate and parameter-free description of the valley dynamics. By using an atomistic, ab initio, approach we fully disclose the elemental mechanisms that dictate the depolarization effects. Our results are in excellent agreement with recent time-dependent Kerr experiments. We explain the Kerr dynamics and its temperature dependence in terms of electron-phonon mediated processes that induce spin-flip inter-valley transitions.

Electromechanical coupling in rat basilar artery in response to morphine.

PubMed

Waters, A; Harder, D R

1983-12-01

Force development, intracellular membrane potential (Em), and voltage vs. current curves were measured in rat basilar artery to help elucidate the mechanism of action of morphine sulfate and a synthetic narcotic, meperidine hydrochloride, on this preparation. Morphine sulfate caused a dose-dependent contraction of these vessels, which was reversible with naloxone. Electrical studies show that morphine may act upon this vascular smooth muscle preparation by decreasing potassium conductance (gk). This hypothesis is supported by the findings that morphine sulfate depolarized these cells and increased the input resistance (rin) determined by the application of rectangular hyperpolarizing and depolarizing current pulses through the microelectrode during impalement and recording of the associated voltage changes (delta V). Meperidine hydrochloride had significantly less effect on this preparation than morphine sulfate. Further studies show that the vehicular medium used for the commercially available preparation of naloxone (viz. the methyl and propyl esters of p-hydroxybenzoic acid in a ratio of 9:1) is, in vitro, a vasodilator of cerebral vascular smooth muscle.

Electrophysiological characterization of neurons in the dorsolateral pontine REM sleep induction zone of the rat: intrinsic membrane properties and responses to carbachol and orexins

PubMed Central

Brown§, Ritchie E.; Winston, Stuart; Basheer, Radhika; Thakkar, Mahesh M; McCarley, Robert W.

2006-01-01

Pharmacological, lesion and single-unit recording techniques in several animal species have identified a region of the pontine reticular formation (Subcoeruleus, SubC) just ventral to the locus coeruleus as critically involved in the generation of rapid-eye-movement (REM) sleep. However, the intrinsic membrane properties and responses of SubC neurons to neurotransmitters important in REM sleep control, such as acetylcholine and orexins/hypocretins, have not previously been examined in any animal species and thus were targeted in this study. We obtained whole-cell patch-clamp recordings from visually identified SubC neurons in rat brain slices in vitro. Two groups of large neurons (mean diameter 30 and 27μm) were tentatively identified as cholinergic (rostral SubC) and noradrenergic (caudal SubC) neurons. SubC reticular neurons (non-cholinergic, non-noradrenergic) showed a medium-sized depolarizing sag during hyperpolarizing current pulses and often had a rebound depolarization (low-threshold spike, LTS). During depolarizing current pulses they exhibited little adaptation and fired maximally at 30–90 Hz. Those SubC reticular neurons excited by carbachol (n=27) fired spontaneously at 6 Hz, often exhibited a moderately sized LTS, and varied widely in size (17–42 μm). Carbachol-inhibited SubC reticular neurons were medium-sized (15–25 μm) and constituted two groups. The larger group (n=22) was silent at rest and possessed a prominent LTS and associated 1–4 action potentials. The second, smaller group (n=8) had a delayed return to baseline at the offset of hyperpolarizing pulses. Orexins excited both carbachol excited and carbachol inhibited SubC reticular neurons. SubC reticular neurons had intrinsic membrane properties and responses to carbachol similar to those described for other reticular neurons but a larger number of carbachol inhibited neurons were found (> 50 %), the majority of which demonstrated a prominent LTS and may correspond to PGO-on neurons. Some or all carbachol-excited neurons are presumably REM-on neurons. PMID:17008019

Electrical filtering in gerbil isolated type I semicircular canal hair cells

NASA Technical Reports Server (NTRS)

Rennie, K. J.; Ricci, A. J.; Correia, M. J.

1996-01-01

1. Membrane potential responses of dissociated gerbil type I semicircular canal hair cells to current injections in whole cell current-clamp have been measured. The input resistance of type I cells was 21.4 +/- 14.3 (SD) M omega, (n = 25). Around the zero-current potential (Vz = -66.6 +/- 9.3 mV, n = 25), pulsed current injections (from approximately -200 to 750 pA) produced only small-amplitude, pulse-like changes in membrane potential. 2. Injecting constant current to hyperpolarize the membrane to around -100 mV resulted in a approximately 10-fold increase in membrane resistance. Current pulses superimposed on this constant hyperpolarization produced larger and more complex membrane potential changes. Depolarizing currents > or = 200 pA caused a rapid transient peak voltage before a plateau. 3. Membrane voltage was able to faithfully follow sine-wave current injections around Vz over the range 1-1,000 Hz with < 25% attenuation at 1 kHz. A previously described K conductance, IKI, which is active at Vz, produces the low input resistance and frequency response. This was confirmed by pharmacologically blocking IKI. This conductance, present in type I cells but not type II hair cells, would appear to confer on type I cells a lower gain, but a much broader bandwidth at Vz, than seen in type II cells.

Sodium influxes in internally perfused squid giant axon during voltage clamp.

PubMed

Atwater, I; Bezanilla, F; Rojas, E

1969-05-01

1. An experimental method for measuring ionic influxes during voltage clamp in the giant axon of Dosidicus is described; the technique combines intracellular perfusion with a method for controlling membrane potential.2. Sodium influx determinations were carried out while applying rectangular pulses of membrane depolarization. The ratio ;measured sodium influx/computed ionic flux during the early current' is 0.92 +/- 0.12.3. Plots of measured sodium influx and computed ionic flux during the early current against membrane potential are very similar. There was evidence that the membrane potential at which the sodium influx vanishes is the potential at which the early current reverses.

Transmitter responsiveness in two newly isolated clones of neuroblastoma X glioma hybrid.

PubMed

Ogura, A; Amano, T

1983-01-10

Mouse neuroblastoma clone N1E-115 cells and rat glioma clone C6 cells were hybridized and two new clones were isolated. One clone, designated NG115-301, possessed weak electric excitability to an applied current pulse, while another clone, NG115-401, generated an action potential in response to the pulse. The former clone responded to serotonin and catecholamines with slow hyperpolarizations, while the latter clone responded to catecholamines with transient depolarizations. Both clones did not respond to acetylcholine. These types of responses have not been reported in any available clones. These clones may enrich the repertoire of cell clones useful for the characterization of transmitter reception mechanisms in the nervous system.

Spreading convulsions, spreading depolarization and epileptogenesis in human cerebral cortex

PubMed Central

Major, Sebastian; Pannek, Heinz-Wolfgang; Woitzik, Johannes; Scheel, Michael; Wiesenthal, Dirk; Martus, Peter; Winkler, Maren K.L.; Hartings, Jed A.; Fabricius, Martin; Speckmann, Erwin-Josef; Gorji, Ali

2012-01-01

Spreading depolarization of cells in cerebral grey matter is characterized by massive ion translocation, neuronal swelling and large changes in direct current-coupled voltage recording. The near-complete sustained depolarization above the inactivation threshold for action potential generating channels initiates spreading depression of brain activity. In contrast, epileptic seizures show modest ion translocation and sustained depolarization below the inactivation threshold for action potential generating channels. Such modest sustained depolarization allows synchronous, highly frequent neuronal firing; ictal epileptic field potentials being its electrocorticographic and epileptic seizure its clinical correlate. Nevertheless, Leão in 1944 and Van Harreveld and Stamm in 1953 described in animals that silencing of brain activity induced by spreading depolarization changed during minimal electrical stimulations. Eventually, epileptic field potentials were recorded during the period that had originally seen spreading depression of activity. Such spreading convulsions are characterized by epileptic field potentials on the final shoulder of the large slow potential change of spreading depolarization. We here report on such spreading convulsions in monopolar subdural recordings in 2 of 25 consecutive aneurismal subarachnoid haemorrhage patients in vivo and neocortical slices from 12 patients with intractable temporal lobe epilepsy in vitro. The in vitro results suggest that γ-aminobutyric acid-mediated inhibition protects from spreading convulsions. Moreover, we describe arterial pulse artefacts mimicking epileptic field potentials in three patients with subarachnoid haemorrhage that ride on the slow potential peak. Twenty-one of the 25 subarachnoid haemorrhage patients (84%) had 656 spreading depolarizations in contrast to only three patients (12%) with 55 ictal epileptic events isolated from spreading depolarizations. Spreading depolarization frequency and depression periods per 24 h recording episodes showed an early and a delayed peak on Day 7. Patients surviving subarachnoid haemorrhage with poor outcome at 6 months showed significantly higher total and peak numbers of spreading depolarizations and significantly longer total and peak depression periods during the electrocorticographic monitoring than patients with good outcome. In a semi-structured telephone interview 3 years after the initial haemorrhage, 44% of the subarachnoid haemorrhage survivors had developed late post-haemorrhagic seizures requiring anti-convulsant medication. In those patients, peak spreading depolarization number had been significantly higher [15.1 (11.4–30.8) versus 7.0 (0.8–11.2) events per day, P = 0.045]. In summary, monopolar recordings here provided unequivocal evidence of spreading convulsions in patients. Hence, practically all major pathological cortical network events in animals have now been observed in people. Early spreading depolarizations may indicate a risk for late post-haemorrhagic seizures. PMID:22120143

Kv7/KCNQ/M and HCN/h, but not KCa2/SK channels, contribute to the somatic medium after-hyperpolarization and excitability control in CA1 hippocampal pyramidal cells

PubMed Central

Gu, Ning; Vervaeke, Koen; Hu, Hua; Storm, Johan F

2005-01-01

In hippocampal pyramidal cells, a single action potential (AP) or a burst of APs is followed by a medium afterhyperpolarization (mAHP, lasting ∼0.1 s). The currents underlying the mAHP are considered to regulate excitability and cause early spike frequency adaptation, thus dampening the response to sustained excitatory input relative to responses to abrupt excitation. The mAHP was originally suggested to be primarily caused by M-channels (at depolarized potentials) and h-channels (at more negative potentials), but not SK channels. In recent reports, however, the mAHP was suggested to be generated mainly by SK channels or only by h-channels. We have now re-examined the mechanisms underlying the mAHP and early spike frequency adaptation in CA1 pyramidal cells by using sharp electrode and whole-cell recording in rat hippocampal slices. The specific M-channel blocker XE991 (10 μm) suppressed the mAHP following 1–5 APs evoked by current injection at −60 mV. XE991 also enhanced the excitability of the cell, i.e. increased the number of APs evoked by a constant depolarizing current pulse, reduced their rate of adaptation, enhanced the afterdepolarization and promoted bursting. Conversely, the M-channel opener retigabine reduced excitability. The h-channel blocker ZD7288 (4-ethylphenylamino-1,2-dimethyl-6-methylaminopyrimidinium chloride; 10 μm) fully suppressed the mAHP at −80 mV, but had little effect at −60 mV, whereas XE991 did not measurably affect the mAHP at −80 mV. Likewise, ZD7288 had little or no effect on excitability or adaptation during current pulses injected from −60 mV, but changed the initial discharge during depolarizing pulses injected from −80 mV. In contrast to previous reports, we found that blockade of Ca2+-activated K+ channels of the SK/KCa type by apamin (100–400 nm) failed to affect the mAHP or adaptation. A computational model of a CA1 pyramidal cell predicted that M- and h-channels will generate mAHPs in a voltage-dependent manner, as indicated by the experiments. We conclude that M- and h-channels generate the somatic mAHP in hippocampal pyramidal cells, with little or no net contribution from SK channels. PMID:15890705

Action potentials in primary osteoblasts and in the MG-63 osteoblast-like cell line.

PubMed

Pangalos, Maria; Bintig, Willem; Schlingmann, Barbara; Feyerabend, Frank; Witte, Frank; Begandt, Daniela; Heisterkamp, Alexander; Ngezahayo, Anaclet

2011-06-01

Whole-cell patch-clamp analysis revealed a resting membrane potential of -60 mV in primary osteoblasts and in the MG-63 osteoblast-like cells. Depolarization-induced action potentials were characterized by duration of 60 ms, a minimal peak-to-peak distance of 180 ms, a threshold value of -20 mV and a repolarization between the spikes to -45 mV. Expressed channels were characterized by application of voltage pulses between -150 mV and 90 mV in 10 mV steps, from a holding potential of -40 mV. Voltages below -60 mV induced an inward current. Depolarizing voltages above -30 mV evoked two currents: (a) a fast activated and inactivated inward current at voltages between -30 and 30 mV, and (b) a delayed-activated outward current that was induced by voltages above -30 mV. Electrophysiological and pharmacological parameters indicated that hyperpolarization activated strongly rectifying K(+) (K(ir)) channels, whereas depolarization activated tetrodotoxin sensitive voltage gated Na(+) (Na(v)) channels as well as delayed, slowly activated, non-inactivating, and tetraethylammonium sensitive voltage gated K(+) (K(v)) channels. In addition, RT-PCR showed expression of Na(v)1.3, Na(v)1.4, Na(v)1.5, Na(v)1.6, Na(v)1.7, and K(ir)2.1, K(ir)2.3, and K(ir)2.4 as well as K(v)2.1. We conclude that osteoblasts express channels that allow firing of action potentials.

Kinetic and pharmacological properties distinguishing three types of calcium currents in chick sensory neurones.

PubMed Central

Fox, A P; Nowycky, M C; Tsien, R W

1987-01-01

1. Calcium currents in cultured dorsal root ganglion (d.r.g.) cells were studied with the whole-cell patch-clamp technique. Using experimental conditions that suppressed Na+ and K+ currents, and 3-10 mM-external Ca2+ or Ba2+, we distinguished three distinct types of calcium currents (L, T and N) on the basis of voltage-dependent kinetics and pharmacology. 2. Component L activates at relatively positive test potentials (t.p. greater than -10 mV) and shows little inactivation during a 200 ms depolarization. It is completely reprimed at a holding potential (h.p.) of -60 mV, and can be isolated by using a more depolarized h.p. (-40 mV) to inactivate the other two types of calcium currents. 3. Component T can be seen in isolation with weak test pulses. It begins activating at potentials more positive than -70 mV and inactivates quickly and completely during a maintained depolarization (time constant, tau approximately 20-50 ms). The current amplitude and the rate of decay increase with stronger depolarizations until both reach a maximum at approximately -40 mV. Inactivation is complete at h.p. greater than -60 mV and is progressively removed between -60 and -95 mV. 4. Component N activates at relatively strong depolarizations (t.p. greater than -20 mV) and decays with time constants ranging from 50 to 110 ms. Inactivation is removed over a very broad range of holding potentials (h.p. between -40 and -110 mV). 5. With 10 mM-EGTA in the pipette solution, substitution of Ba2+ for Ca2+ as the charge carrier does not alter the rates of activation or relaxation of any component. However, T-type channels are approximately equally permeable to Ca2+ and Ba2+, while L-type and N-type channels are both much more permeable to Ba2+. 6. Component N cannot be explained by current-dependent inactivation of L current resulting from recruitment of extra L-type channels at negative holding potentials: raising the external Ba2+ concentration to 110 mM greatly increases the amplitude of L current evoked from h.p. = -30 mV but produces little inactivation. 7. Cadmium ions (20-50 microM) virtually eliminate both N and L currents (greater than 90% block) but leave T relatively unaffected (less than 50% block). 200 microM-Cd2+ blocks all three components. 8. Nickel ions (100 microM) strongly reduce T current but leave N and L current little changed. 9. The dihydropyridine antagonist nifedipine (10 microM) inhibits L current (approximately 60% block) at a holding potential that inactivates half the L-type channels.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:2451016

Voltage-Clamp Studies on Uterine Smooth Muscle

PubMed Central

Anderson, Nels C.

1969-01-01

These studies have developed and tested an experimental approach to the study of membrane ionic conductance mechanisms in strips of uterine smooth muscle. The experimental and theoretical basis for applying the double sucrose-gap technique is described along with the limitations of this system. Nonpropagating membrane action potentials were produced in response to depolarizing current pulses under current-clamp conditions. The stepwise change of membrane potential under voltage-clamp conditions resulted in a family of ionic currents with voltage- and time-dependent characteristics. In sodium-free solution the peak transient current decreased and its equilibrium potential shifted along the voltage axis toward a more negative internal potential. These studies indicate a sodium-dependent, regenerative excitation mechanism. PMID:5796366

Sodium influxes in internally perfused squid giant axon during voltage clamp

PubMed Central

Atwater, I.; Bezanilla, F.; Rojas, E.

1969-01-01

1. An experimental method for measuring ionic influxes during voltage clamp in the giant axon of Dosidicus is described; the technique combines intracellular perfusion with a method for controlling membrane potential. 2. Sodium influx determinations were carried out while applying rectangular pulses of membrane depolarization. The ratio `measured sodium influx/computed ionic flux during the early current' is 0·92 ± 0·12. 3. Plots of measured sodium influx and computed ionic flux during the early current against membrane potential are very similar. There was evidence that the membrane potential at which the sodium influx vanishes is the potential at which the early current reverses. PMID:5767887

Block of calcium channels by enkephalin and somatostatin in neuroblastoma-glioma hybrid NG108-15 cells.

PubMed

Tsunoo, A; Yoshii, M; Narahashi, T

1986-12-01

Leucine-enkephalin, methionine-enkephalin, and morphine caused a reversible block of Ca2+ channel currents in neuroblastoma-glioma hybrid cells (NG108-15). The long-lasting (type 2) component of the Ca2+ channel current was blocked by leucine-enkephalin, while the transient (type 1) component was not affected. The enkephalin-induced blocking action was antagonized by naloxone and appears to be mediated by delta-opiate receptors. Two different aspects of the blocking effect were detected, a resting block and a recovery from block during prolonged depolarizing pulses. Recovery from block was more complete, and its time course was more rapid, with depolarization to more positive potentials. The dose dependence of the type 2 channel block at rest indicated a one-to-one binding stoichiometry, with an apparent dissociation constant of 8.8 nM. Somatostatin exerted a similar selective blocking action on the type 2 Ca2+ channel. The time- and voltage-dependent block of type 2 Ca2+ channels may provide a mechanism underlying the enkephalinergic presynaptic inhibition of transmitter release and the somatostatin block of pituitary growth hormone release.

Airborne Polarized Lidar Detection of Scattering Layers in the Ocean

NASA Astrophysics Data System (ADS)

Vasilkov, Alexander P.; Goldin, Yury A.; Gureev, Boris A.; Hoge, Frank E.; Swift, Robert N.; Wright, C. Wayne

2001-08-01

A polarized lidar technique based on measurements of waveforms of the two orthogonal-polarized components of the backscattered light pulse is proposed to retrieve vertical profiles of the seawater scattering coefficient. The physical rationale for the polarized technique is that depolarization of backscattered light originating from a linearly polarized laser beam is caused largely by multiple small-angle scattering from particulate matter in seawater. The magnitude of the small-angle scattering is determined by the scattering coefficient. Therefore information on the vertical distribution of the scattering coefficient can be derived potentially from measurements of the timedepth dependence of depolarization in the backscattered laser pulse. The polarized technique was verified by field measurements conducted in the Middle Atlantic Bight of the western North Atlantic Ocean that were supported by in situ measurements of the beam attenuation coefficient. The airborne polarized lidar measured the timedepth dependence of the backscattered laser pulse in two orthogonal-polarized components. Vertical profiles of the scattering coefficient retrieved from the timedepth depolarization of the backscattered laser pulse were compared with measured profiles of the beam attenuation coefficient. The comparison showed that retrieved profiles of the scattering coefficient clearly reproduce the main features of the measured profiles of the beam attenuation coefficient. Underwater scattering layers were detected at depths of 2025 m in turbid coastal waters. The improvement in dynamic range afforded by the polarized lidar technique offers a strong potential benefit for airborne lidar bathymetric applications.

Fluorescence/depolarization lidar for mid-range stand-off detection of biological agents

NASA Astrophysics Data System (ADS)

Mierczyk, Z.; Kopczyński, K.; Zygmunt, M.; Wojtanowski, J.; Młynczak, J.; Gawlikowski, A.; Młodzianko, A.; Piotrowski, W.; Gietka, A.; Knysak, P.; Drozd, T.; Muzal, M.; Kaszczuk, M.; Ostrowski, R.; Jakubaszek, M.

2011-06-01

LIDAR system for real-time standoff detection of bio-agents is presented and preliminary experimental results are discussed. The detection approach is based on two independent physical phenomena: (1) laser induced fluorescence (LIF), (2) depolarization resulting from elastic scattering on non-spherical particles. The device includes three laser sources, two receiving telescopes, depolarization component and spectral signature analyzing spectrograph. It was designed to provide the stand-off detection capability at ranges from 200 m up to several kilometers. The system as a whole forms a mobile platform for vehicle or building installation. Additionally, it's combined with a scanning mechanics and advanced software, which enable to conduct the semi-automatic monitoring of a specified space sector. For fluorescence excitation, 3-rd (355 nm) and 4-th (266 nm) harmonics of Nd:YAG pulsed lasers are used. They emit short (~6 ns) pulses with the repetition rate of 20 Hz. Collecting optics for fluorescence echo detection and spectral content analysis includes 25 mm diameter f/4 Newton telescope, Czerny Turner spectrograph and 32-channel PMT. Depending on the grating applied, the spectral resolution from 20 nm up to 3 nm per channel can be achieved. The system is also equipped with an eye-safe (1.5 μm) Nd:YAG OPO laser for elastic backscattering/depolarization detection. The optical echo signal is collected by Cassegrain telescope with aperture diameter of 12.5 mm. Depolarization detection component based on polarizing beam-splitter serves as the stand-off particle-shape analyzer, which is very valuable in case of non-spherical bio-aerosols sensing.

Depression of voltage-activated Ca2+ release in skeletal muscle by activation of a voltage-sensing phosphatase

PubMed Central

Berthier, Christine; Kutchukian, Candice; Bouvard, Clément; Okamura, Yasushi

2015-01-01

Phosphoinositides act as signaling molecules in numerous cellular transduction processes, and phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) regulates the function of several types of plasma membrane ion channels. We investigated the potential role of PtdIns(4,5)P2 in Ca2+ homeostasis and excitation–contraction (E-C) coupling of mouse muscle fibers using in vivo expression of the voltage-sensing phosphatases (VSPs) Ciona intestinalis VSP (Ci-VSP) or Danio rerio VSP (Dr-VSP). Confocal images of enhanced green fluorescent protein–tagged Dr-VSP revealed a banded pattern consistent with VSP localization within the transverse tubule membrane. Rhod-2 Ca2+ transients generated by 0.5-s-long voltage-clamp depolarizing pulses sufficient to elicit Ca2+ release from the sarcoplasmic reticulum (SR) but below the range at which VSPs are activated were unaffected by the presence of the VSPs. However, in Ci-VSP–expressing fibers challenged by 5-s-long depolarizing pulses, the Ca2+ level late in the pulse (3 s after initiation) was significantly lower at 120 mV than at 20 mV. Furthermore, Ci-VSP–expressing fibers showed a reversible depression of Ca2+ release during trains, with the peak Ca2+ transient being reduced by ∼30% after the application of 10 200-ms-long pulses to 100 mV. A similar depression was observed in Dr-VSP–expressing fibers. Cav1.1 Ca2+ channel–mediated current was unaffected by Ci-VSP activation. In fibers expressing Ci-VSP and a pleckstrin homology domain fused with monomeric red fluorescent protein (PLCδ1PH-mRFP), depolarizing pulses elicited transient changes in mRFP fluorescence consistent with release of transverse tubule–bound PLCδ1PH domain into the cytosol; the voltage sensitivity of these changes was consistent with that of Ci-VSP activation, and recovery occurred with a time constant in the 10-s range. Our results indicate that the PtdIns(4,5)P2 level is tightly maintained in the transverse tubule membrane of the muscle fibers, and that VSP-induced depletion of PtdIns(4,5)P2 impairs voltage-activated Ca2+ release from the SR. Because Ca2+ release is thought to be independent from InsP3 signaling, the effect likely results from an interaction between PtdIns(4,5)P2 and a protein partner of the E-C coupling machinery. PMID:25825170

Depression of voltage-activated Ca2+ release in skeletal muscle by activation of a voltage-sensing phosphatase.

PubMed

Berthier, Christine; Kutchukian, Candice; Bouvard, Clément; Okamura, Yasushi; Jacquemond, Vincent

2015-04-01

Phosphoinositides act as signaling molecules in numerous cellular transduction processes, and phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) regulates the function of several types of plasma membrane ion channels. We investigated the potential role of PtdIns(4,5)P2 in Ca(2+) homeostasis and excitation-contraction (E-C) coupling of mouse muscle fibers using in vivo expression of the voltage-sensing phosphatases (VSPs) Ciona intestinalis VSP (Ci-VSP) or Danio rerio VSP (Dr-VSP). Confocal images of enhanced green fluorescent protein-tagged Dr-VSP revealed a banded pattern consistent with VSP localization within the transverse tubule membrane. Rhod-2 Ca(2+) transients generated by 0.5-s-long voltage-clamp depolarizing pulses sufficient to elicit Ca(2+) release from the sarcoplasmic reticulum (SR) but below the range at which VSPs are activated were unaffected by the presence of the VSPs. However, in Ci-VSP-expressing fibers challenged by 5-s-long depolarizing pulses, the Ca(2+) level late in the pulse (3 s after initiation) was significantly lower at 120 mV than at 20 mV. Furthermore, Ci-VSP-expressing fibers showed a reversible depression of Ca(2+) release during trains, with the peak Ca(2+) transient being reduced by ∼30% after the application of 10 200-ms-long pulses to 100 mV. A similar depression was observed in Dr-VSP-expressing fibers. Cav1.1 Ca(2+) channel-mediated current was unaffected by Ci-VSP activation. In fibers expressing Ci-VSP and a pleckstrin homology domain fused with monomeric red fluorescent protein (PLCδ1PH-mRFP), depolarizing pulses elicited transient changes in mRFP fluorescence consistent with release of transverse tubule-bound PLCδ1PH domain into the cytosol; the voltage sensitivity of these changes was consistent with that of Ci-VSP activation, and recovery occurred with a time constant in the 10-s range. Our results indicate that the PtdIns(4,5)P2 level is tightly maintained in the transverse tubule membrane of the muscle fibers, and that VSP-induced depletion of PtdIns(4,5)P2 impairs voltage-activated Ca(2+) release from the SR. Because Ca(2+) release is thought to be independent from InsP3 signaling, the effect likely results from an interaction between PtdIns(4,5)P2 and a protein partner of the E-C coupling machinery. © 2015 Berthier et al.

Structure-activity relationships for the action of 11 pyrethroid insecticides on rat Na{sub v}1.8 sodium channels expressed in Xenopus oocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Choi, J.-S.; Soderlund, David M.

2006-03-15

Pyrethroid insecticides bind to voltage-sensitive sodium channels and modify their gating kinetics, thereby disrupting nerve function. This paper describes the action of 11 structurally diverse commercial pyrethroid insecticides on the rat Na{sub v}1.8 sodium channel isoform, the principal carrier of the tetrodotoxin-resistant, pyrethroid-sensitive sodium current of sensory neurons, expressed in Xenopus laevis oocytes. All 11 compounds produced characteristic sodium tail currents following a depolarizing pulse that ranged from rapidly-decaying monoexponential currents (allethrin, cismethrin and permethrin) to persistent biexponential currents (cyfluthrin, cyhalothrin, cypermethrin and deltamethrin). Tail currents for the remaining compounds (bifenthrin, fenpropathrin, fenvalerate and tefluthrin) were monoexponential and decayed withmore » kinetics intermediate between these extremes. Reconstruction of currents carried solely by the pyrethroid-modified subpopulation of channels revealed two types of pyrethroid-modified currents. The first type, found with cismethrin, allethrin, permethrin and tefluthrin, activated relatively rapidly and inactivated partially during a 40-ms depolarization. The second type, found with cypermethrin, cyfluthrin, cyhalothrin, deltamethrin, fenpropathrin and fenvalerate, activated more slowly and did not detectably inactivate during a 40-ms depolarization. Only bifenthrin did not produce modified currents that fit clearly into either of these categories. In all cases, the rate of activation of modified channels was strongly correlated with the rate of tail current decay following repolarization. Modification of Na{sub v}1.8 sodium channels by cyfluthrin, cyhalothrin, cypermethrin and deltamethrin was enhanced 2.3- to 3.4-fold by repetitive stimulation; this effect appeared to result from the accumulation of persistently open channels rather than preferential binding to open channel states. Fenpropathrin was the most effective compound against Na{sub v}1.8 sodium channels from the perspective of either resting or use-dependent modification. When use dependence is taken into account, cypermethrin, deltamethrin and tefluthrin approached the effectiveness of fenpropathrin. The selective expression of Na{sub v}1.8 sodium channels in nociceptive neurons suggests that these channels may be important targets for pyrethroids in the production of paresthesia following dermal expo0010su.« less

Intrinsic Membrane Properties of Pre-oromotor Neurons in the Intermediate Zone of the Medullary Reticular Formation

PubMed Central

Venugopal, Sharmila; Boulant, Jack A.; Chen, Zhixiong; Travers, Joseph B.

2010-01-01

Neurons in the lower brainstem that control consummatory behavior are widely distributed in the reticular formation (RF) of the pons and medulla. The intrinsic membrane properties of neurons within this distributed system shape complex excitatory and inhibitory inputs from both orosensory and central structures implicated in homeostatic control to produce coordinated oromotor patterns. The current study explored the intrinsic membrane properties of neurons in the intermediate subdivision of the medullary reticular formation (IRt). Neurons in the IRt receive input from the overlying (gustatory) nucleus of the solitary tract and project to the oromotor nuclei. Recent behavioral pharmacology studies as well as computational modeling suggest that inhibition in the IRt plays an important role in the transition from a taste-initiated oromotor pattern of ingestion to one of rejection. The present study explored the impact of hyperpolarization on membrane properties. In response to depolarization, neurons responded with either a tonic discharge, an irregular/burst pattern or were spike-adaptive. A hyperpolarizing pre-pulse modulated the excitability of most (82%) IRt neurons to subsequent depolarization. Instances of both increased (30%) and decreased (52%) excitability were observed. Currents induced by the hyperpolarization included an outward 4-AP sensitive K+ current that suppressed excitability and an inward cation current that increased excitability. These currents are also present in other subpopulations of RF neurons that influence the oromotor nuclei and we discuss how these currents could alter ring characteristics to impact pattern generation. PMID:20338224

Theoretical analysis of shock induced depolarization and current generation in ferroelectrics

NASA Astrophysics Data System (ADS)

Agrawal, Vinamra; Bhattacharya, Kaushik

Ferroelectric generators are used to generate large magnitude current pulse by impacting a polarized ferroelectric material. The impact causes depolarization of the material and at high impact speeds, dielectric breakdown. Depending on the loading conditions and the electromechanical boundary conditions, the current or voltage profiles obtained vary. In this study, we explore the large deformation dynamic response of a ferroelectric material. Using the Maxwell's equations, conservation laws and the second law of thermodynamics, we derive the governing equations for the phase boundary propagation as well as the driving force acting on it. We allow for the phase boundary to contain surface charges which introduces the contribution of curvature of phase boundary in the governing equations and the driving force. This type of analysis accounts for the dielectric breakdown and resulting conduction in the material. Next, we implement the equations derived to solve a one dimensional impact problem on a ferroelectric material under different electrical boundary conditions. The constitutive law is chosen to be piecewise quadratic in polarization and quadratic in the strain. We solve for the current profile generated in short circuit case and for voltage profile in open circuited case. This work was made possible by the financial support of the US Air Force Office of Scientific Research through the Center of Excellence in High Rate Deformation Physics of Heterogeneous Materials (Grant: FA 9550-12-1-0091).

Neodymium glass laser with a phase conjugate mirror producing 220 J pulses at 0.02 Hz repetition rate.

PubMed

Kuzmin, A A; Khazanov, E A; Kulagin, O V; Shaykin, A A

2014-08-25

For pumping multipetawatt Ti:sapphire laser facilities we developed a compact repetitively pulsed laser based on neodymium phosphate glass with pulse energy of 220 J, pulse repetition rate of 0.02 Hz, beam diameter of 43 mm, aperture fill factor of 0.8, and FWHM pulse duration of 30 ns. The phase distortions of laser radiation were compensated by optical phase conjugation via stimulated Brillouin scattering. The depolarization was reduced to 0.4% using linear compensation methods. The beam quality was 2.5 x diffraction limit (150 µrad).

Dynamic fiber delivery of 3 W 160 fs pulses with photonic crystal hollow core fiber patchcord

NASA Astrophysics Data System (ADS)

Resan, Bojan; Auchli, Raffael; Holtz, Ronald

2017-02-01

We report output characteristics from the FC/APC connectorized photonics crystal hollow core fiber when is subjected to coiling down to 50 mm radius, bending, torsion etc. We achieved coupling efficiency up to 75%, output average power 2 W and 24 nJ pulse energy. With proper coupling the depolarization could be as low as 7%. Torsion of the photonic crystal patchcord destroys the polarization and other pulse properties.

Bepridil differentially inhibits two delayed rectifier K+ currents, IKr and IKs, in guinea-pig ventricular myocytes

PubMed Central

Wang, Jin-Cheng; Kiyosue, Tatsuto; Kiriyama, Kuninori; Arita, Makoto

1999-01-01

We investigated the effects of bepridil on the two components of the delayed rectifier K+ current, i.e., the rapidly activating (IKr) and the slowly activating (IKs) currents using tight-seal whole-cell patch-clamp techniques in guinea-pig ventricular myocytes, under blockade of L-type Ca2+ current with nitrendipine (5 μM) or D600 (1 μM).Bepridil decreased IKs under blockade of IKr with E4031 (5 μM), in a concentration-dependent manner. The concentration-dependent inhibition of IKs by bepridil was fitted by a curve, assuming one-to-one interactions between the channel and the drug molecule. The concentration of half-maximal inhibition (IC50) was found to be 6.2 μM.The effect of bepridil on IKr was assessed using an envelope-of-tails test. In the control condition, a ratio of the tail current to the time-dependent current measured during depolarization was large (>1) at shorter pulses (<200 ms), and it decreased to a steady state value of ∼0.4 with increases in the pulse duration. Bepridil at a concentration of 2 μM did not decrease this ratio at shorter pulses.In a short-pulse (duration=50 ms) experiment that largely activates IKr, the drug was found to block IKr in a cooperative manner (Hill coefficient=3.03) and the IC50 was 13.2 μM.These results suggest that bepridil at a clinical therapeutic concentration (∼2 μM) selectively blocks IKs but does not inhibit IKr. This may relate to the characteristic frequency-dependent effects of bepridil on the action potential duration (APD), e.g., the non-reverse use-dependent prolongation of APD. PMID:10588929

Initial data from a new High Spectral Resolution Lidar. Appendix A

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eloranta, E.W.; Piironen, P.K.

1993-12-31

The University of Wisconsin High Spectral Resolution Lidar (HSRL) has been recently redesigned for operation in an electronics semitrailer van. The HSRL can now be deployed in support of field experiments. This paper presents initial observations with the new configuration along with an analysis of measurement accuracy. New measurement capabilities have been added. These include: observation of the signal variation with angular field of view, and observation of depolarization in all data channels. Depolarization measurements have been implemented by transmitting orthogonal linear polarizations on alternate laser pulses. Pulses are transmitted at 250 {micro}s intervals such that the lidar observes themore » same ensemble of particles for both polarizations. Orthogonal polarizations are measured with a single detector per channel. Since the optical components and detector gains are identical for the two polarizations the measured depolarization ratios are independent of these factors and the system delivers very precise depolarizations. A new data channel with a computer controlled aperture allows measurements of multiple scattering as a function of receiver field of view. Since the field of view variation is dependent on the size of the scattering particles it is expected that this will allow remote measurements of cloud particle size. Other technical improvements in the new system include active control of spectrometer temperatures, greatly increased mechanical stability, an increased receiver aperture, injection of calibration signals into the signal profiles to allow continuous monitoring of system calibration drifts, and extensive computer control of system operations.« less

Potassium channels cloned from neuroblastoma cells display slowly inactivating outward currents in Xenopus oocytes.

PubMed

Ito, Y; Yokoyama, S; Higashida, H

1992-05-22

Messenger RNAs (mRNAs) specific for NGK1 and NGK2 potassium channels were synthesized from complementary DNAs (cDNAs) that had been cloned from mouse neuroblastoma x rat glioma hybrid NG108-15 cells. Outward pottasium currents were evoked by 5 s depolarizing voltage commands in Xenopus oocytes injected with NGK1- or NGK2-specific mRNAs. The NGK1 or NGK2 currents showed different activation and inactivation kinetics, and different pharmacological sensitivities. The threshold potential for activation of the NGK2 current (-14 mV) was more positive than that for the NGK1 (-36 mV). The NGK2 current showed faster inactivation during a 5 s depolarizing pulse than did the NGK1 current. Inactivation was best fit by time constants of 0.37, 1.5 and 19 s for the NGK2 current and 4.4 and 19 s for NGK1. Extracellularly applied tetraethylammonium chloride (TEA) was 1000 times more potent on the NGK2 current than the NGK1 current. Furthermore we examined outward current following co-injection of an equal amount of mRNAs for NGK1 and NGK2. The timecourse of inactivation differed from either alone or from a simple sum of the two individual currents. TEA sensitivity could not be explained by summation of the two homomultimeric channels. These findings suggest that both NGK1 and NGK2 proteins assemble to form heteromultimeric K+ channels in addition to homomultimeric K+ channels. NGK2 channels and the heteromultimeric channels may be responsible for the native transient outward current with slow inactivation in NG108-15 hybrid cells.

Transient Response in a Dendritic Neuron Model for Current Injected at One Branch

PubMed Central

Rinzel, John; Rall, Wilfrid

1974-01-01

Mathematical expressions are obtained for the response function corresponding to an instantaneous pulse of current injected to a single dendritic branch in a branched dendritic neuron model. The theoretical model assumes passive membrane properties and the equivalent cylinder constraint on branch diameters. The response function when used in a convolution formula enables one to compute the voltage transient at any specified point in the dendritic tree for an arbitrary current injection at a given input location. A particular numerical example, for a brief current injection at a branch terminal, illustrates the attenuation and delay characteristics of the depolarization peak as it spreads throughout the neuron model. In contrast to the severe attenuation of voltage transients from branch input sites to the soma, the fraction of total input charge actually delivered to the soma and other trees is calculated to be about one-half. This fraction is independent of the input time course. Other numerical examples, which compare a branch terminal input site with a soma input site, demonstrate that, for a given transient current injection, the peak depolarization is not proportional to the input resistance at the injection site and, for a given synaptic conductance transient, the effective synaptic driving potential can be significantly reduced, resulting in less synaptic current flow and charge, for a branch input site. Also, for the synaptic case, the two inputs are compared on the basis of the excitatory post-synaptic potential (EPSP) seen at the soma and the total charge delivered to the soma. PMID:4424185

Intrinsic membrane properties of pre-oromotor neurons in the intermediate zone of the medullary reticular formation.

PubMed

Venugopal, S; Boulant, J A; Chen, Z; Travers, J B

2010-06-16

Neurons in the lower brainstem that control consummatory behavior are widely distributed in the reticular formation (RF) of the pons and medulla. The intrinsic membrane properties of neurons within this distributed system shape complex excitatory and inhibitory inputs from both orosensory and central structures implicated in homeostatic control to produce coordinated oromotor patterns. The current study explored the intrinsic membrane properties of neurons in the intermediate subdivision of the medullary reticular formation (IRt). Neurons in the IRt receive input from the overlying (gustatory) nucleus of the solitary tract and project to the oromotor nuclei. Recent behavioral pharmacology studies as well as computational modeling suggest that inhibition in the IRt plays an important role in the transition from a taste-initiated oromotor pattern of ingestion to one of rejection. The present study explored the impact of hyperpolarization on membrane properties. In response to depolarization, neurons responded with either a tonic discharge, an irregular/burst pattern or were spike-adaptive. A hyperpolarizing pre-pulse modulated the excitability of most (82%) IRt neurons to subsequent depolarization. Instances of both increased (30%) and decreased (52%) excitability were observed. Currents induced by the hyperpolarization included an outward 4-aminopyridine (4-AP) sensitive K+ current that suppressed excitability and an inward cation current that increased excitability. These currents are also present in other subpopulations of RF neurons that influence the oromotor nuclei and we discuss how these currents could alter firing characteristics to impact pattern generation. 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

Involvement of histaminergic inputs in the jaw-closing reflex arc

PubMed Central

Gemba, Chikako; Nakayama, Kiyomi; Nakamura, Shiro; Mochizuki, Ayako; Inoue, Tomio

2015-01-01

Histamine receptors are densely expressed in the mesencephalic trigeminal nucleus (MesV) and trigeminal motor nucleus. However, little is known about the functional roles of neuronal histamine in controlling oral-motor activity. Thus, using the whole-cell recording technique in brainstem slice preparations from Wistar rats aged between postnatal days 7 and 13, we investigated the effects of histamine on the MesV neurons innervating the masseter muscle spindles and masseter motoneurons (MMNs) that form a reflex arc for the jaw-closing reflex. Bath application of histamine (100 μM) induced membrane depolarization in both MesV neurons and MMNs in the presence of tetrodotoxin, whereas histamine decreased and increased the input resistance in MesV neurons and MMNs, respectively. The effects of histamine on MesV neurons and MMNs were mimicked by an H1 receptor agonist, 2-pyridylethylamine (100 μM). The effects of an H2 receptor agonist, dimaprit (100 μM), on MesV neurons were inconsistent, whereas MMNs were depolarized without changes in the input resistance. An H3 receptor agonist, immethridine (100 μM), also depolarized both MesV neurons and MMNs without changing the input resistance. Histamine reduced the peak amplitude of postsynaptic currents (PSCs) in MMNs evoked by stimulation of the trigeminal motor nerve (5N), which was mimicked by 2-pyridylethylamine but not by dimaprit or immethridine. Moreover, 2-pyridylethylamine increased the failure rate of PSCs evoked by minimal stimulation and the paired-pulse ratio. These results suggest that histaminergic inputs to MesV neurons through H1 receptors are involved in the suppression of the jaw-closing reflex although histamine depolarizes MesV neurons and/or MMNs. PMID:25904711

Excitation and inhibition compete to control spiking during hippocampal ripples: intracellular study in behaving mice.

PubMed

English, Daniel F; Peyrache, Adrien; Stark, Eran; Roux, Lisa; Vallentin, Daniela; Long, Michael A; Buzsáki, György

2014-12-03

High-frequency ripple oscillations, observed most prominently in the hippocampal CA1 pyramidal layer, are associated with memory consolidation. The cellular and network mechanisms underlying the generation of the rhythm and the recruitment of spikes from pyramidal neurons are still poorly understood. Using intracellular, sharp electrode recordings in freely moving, drug-free mice, we observed consistent large depolarizations in CA1 pyramidal cells during sharp wave ripples, which are associated with ripple frequency fluctuation of the membrane potential ("intracellular ripple"). Despite consistent depolarization, often exceeding pre-ripple spike threshold values, current pulse-induced spikes were strongly suppressed, indicating that spiking was under the control of concurrent shunting inhibition. Ripple events were followed by a prominent afterhyperpolarization and spike suppression. Action potentials during and outside ripples were orthodromic, arguing against ectopic spike generation, which has been postulated by computational models of ripple generation. These findings indicate that dendritic excitation of pyramidal neurons during ripples is countered by shunting of the membrane and postripple silence is mediated by hyperpolarizing inhibition. Copyright © 2014 the authors 0270-6474/14/3316509-09$15.00/0.

Conductivity Variation Observed by Polarization and Depolarization Current Measurements of High-Voltage Equipment Insulation System

NASA Astrophysics Data System (ADS)

Jamail, Nor Akmal Mohd; Piah, Mohamed Afendi Mohamed; Muhamad, Nor Asiah

2012-09-01

Nondestructive and time domain dielectric measurement techniques such as polarization and depolarization current (PDC) measurements have recently been widely used as a potential tool for determining high-voltage insulation conditions by analyzing the insulation conductivity. The variation in the conductivity of an insulator was found to depend on several parameters: the difference between the polarization and depolarization currents, geometric capacitance, and the relative permittivity of the insulation material. In this paper the conductivities of different types of oil-paper insulation material are presented. The insulation conductivities of several types of electrical apparatus were simulated using MATLAB. Conductivity insulation was found to be high at high polarizations and at the lowest depolarization current. It was also found to increase with increasing relative permittivity as well as with decreasing geometric capacitance of the insulating material.

Indistinguishable Synaptic Pharmacodynamics of the N-Methyl-d-Aspartate Receptor Channel Blockers Memantine and Ketamine

PubMed Central

Emnett, Christine M.; Eisenman, Lawrence N.; Taylor, Amanda M.; Izumi, Yukitoshi; Zorumski, Charles F.

2013-01-01

Memantine and ketamine, voltage- and activation-dependent channel blockers of N-methyl-d-aspartate (NMDA) receptors (NMDARs), have enjoyed a recent resurgence in clinical interest. Steady-state pharmacodynamic differences between these blockers have been reported, but it is unclear whether the compounds differentially affect dynamic physiologic signaling. In this study, we explored nonequilibrium conditions relevant to synaptic transmission in hippocampal networks in dissociated culture and hippocampal slices. Equimolar memantine and ketamine had indistinguishable effects on the following measures: steady-state NMDA currents, NMDAR excitatory postsynaptic current (EPSC) decay kinetics, progressive EPSC inhibition during repetitive stimulation, and extrasynaptic NMDAR inhibition. Therapeutic drug efficacy and tolerability of memantine have been attributed to fast kinetics and strong voltage dependence. However, pulse depolarization in drug presence revealed a surprisingly slow and similar time course of equilibration for the two compounds, although memantine produced a more prominent fast component (62% versus 48%) of re-equilibration. Simulations predicted that low gating efficacy underlies the slow voltage–dependent relief from block. This prediction was empirically supported by faster voltage-dependent blocker re-equilibration with several experimental manipulations of gating efficacy. Excitatory postsynaptic potential–like voltage commands produced drug differences only with large, prolonged depolarizations unlikely to be attained physiologically. In fact, we found no difference between drugs on measures of spontaneous network activity or acute effects on plasticity in hippocampal slices. Despite indistinguishable synaptic pharmacodynamics, ketamine provided significantly greater neuroprotection from damage induced by oxygen glucose deprivation, consistent with the idea that under extreme depolarizing conditions, the biophysical difference between drugs becomes detectable. We conclude that despite subtle differences in voltage dependence, during physiologic activity, blocker pharmacodynamics are largely indistinguishable and largely voltage independent. PMID:24101301

Negative Feedback Mediated by Fast Inhibitory Autapse Enhances Neuronal Oscillations Near a Hopf Bifurcation Point

NASA Astrophysics Data System (ADS)

Jia, Bing

One-parameter and two-parameter bifurcations of the Morris-Lecar (ML) neuron model with and without the fast inhibitory autapse, which is a synapse from a neuron onto itself, are investigated. The ML neuron model without autapse manifests an inverse Hopf bifurcation point from firing to a depolarized resting state with high level of membrane potential, with increasing depolarization current. When a fast inhibitory autapse is introduced, a negative feedback or inhibitory current is applied to the ML model. With increasing conductance of the autapse to middle level, the depolarized resting state near the inverse Hopf bifurcation point can change to oscillation and the parameter region of the oscillation becomes wide, which can be well interpreted by the dynamic responses of the depolarized resting state to the inhibitory current stimulus mediated by the autapse. The enlargement of the parameter region of the oscillation induced by the negative feedback presents a novel viewpoint different from the traditional one that inhibitory synapse often suppresses the neuronal oscillation activities. Furthermore, complex nonlinear dynamics such as the coexisting behaviors and codimension-2 bifurcations including the Bautin and cusp bifurcations are acquired. The relationship between the bifurcations and the depolarization block, a physiological concept that indicates a neuron can enter resting state when receiving the depolarization current, is discussed.

Mathematical model of depolarization mechanism of conducted vasoreactivity

NASA Astrophysics Data System (ADS)

Neganova, Anastasiia Y.; Stiukhina, Elena S.; Postnov, Dmitry E.

2015-03-01

We address the problem of conducted vasodilation, the phenomenon which is also known as functional hyperemia. Specifically, we test the mechanism of nondecremental propagation of electric signals along endothelial cell layer recently hypothesized by Figueroa et al. By means of functional modeling we focus on possible nonlinear mechanisms that can underlie such regenerative pulse transmission (RPT). Since endothelial cells (EC) are generally known as electrically inexcitable, the possible role of ECs in RPT mechanisms is not evident. By means of mathematical modeling we check the dynamical self-consistency of Figueroa's hypothesis, as well as estimate the possible contribution of specific ionic currents to the suggested RPT mechanism.

Cardiac transient outward potassium current: a pulse chemistry model of frequency-dependent properties.

PubMed

Liu, L; Krinsky, V I; Grant, A O; Starmer, C F

1996-01-01

Recent voltage-clamp studies of isolated myocytes have demonstrated widespread occurrence of a transient outward current (I(to)) carried by potassium ions. In the canine ventricle, this current is well developed in epicardial cells but not in endocardial cells. The resultant spatial dispersion of refractoriness is potentially proarrhythmic and may be amplified by channel blockade. The inactivation and recovery time constants of this channel are in excess of several hundred milliseconds, and consequently channel availability is frequency dependent at physiological stimulation rates. When the time constants associated with transitions between different channel conformations are rapid relative to drug binding kinetics, the interactions between drugs and an ion channel can be approximated by a sequence of first-order reactions, in which binding occurs in pulses in response to pulse train stimulation (pulse chemistry). When channel conformation transition time constants do not meet this constraint, analytical characterizations of the drug-channel interaction must then be modified to reflect the channel time-dependent properties. Here we report that the rate and steady-state amount of frequency-dependent inactivation of I(to) are consistent with a generalization of the channel blockade model: channel availability is reduced in a pulsatile exponential pattern as the stimulation frequency is increased, and the rate of reduction is a linear function of the pulse train depolarizing and recovery intervals. I(to) was reduced in the presence of quinidine. After accounting for the use-dependent availability of I(to) channels, we found little evidence of an additional use-dependent component of block after exposure to quinidine, suggesting that quinidine reacts with both open and closed I(to) channels as though the binding site is continuously accessible. The model provides a useful tool for assessing drug-channel interactions when the reaction cannot be continuously monitored.

Depolarized inactivation overcomes impaired activation to produce DRG neuron hyperexcitability in a Nav1.7 mutation in a patient with distal limb pain.

PubMed

Huang, Jianying; Yang, Yang; Dib-Hajj, Sulayman D; van Es, Michael; Zhao, Peng; Salomon, Jody; Drenth, Joost P H; Waxman, Stephen G

2014-09-10

Sodium channel Nav1.7, encoded by SCN9A, is expressed in DRG neurons and regulates their excitability. Genetic and functional studies have established a critical contribution of Nav1.7 to human pain disorders. We have now characterized a novel Nav1.7 mutation (R1279P) from a female human subject with distal limb pain, in which depolarized fast inactivation overrides impaired activation to produce hyperexcitability and spontaneous firing in DRG neurons. Whole-cell voltage-clamp recordings in human embryonic kidney (HEK) 293 cells demonstrated that R1279P significantly depolarizes steady-state fast-, slow-, and closed-state inactivation. It accelerates deactivation, decelerates inactivation, and facilitates repriming. The mutation increases ramp currents in response to slow depolarizations. Our voltage-clamp analysis showed that R1279P depolarizes channel activation, a change that was supported by our multistate structural modeling. Because this mutation confers both gain-of-function and loss-of-function attributes on the Nav1.7 channel, we tested the impact of R1279P expression on DRG neuron excitability. Current-clamp studies reveal that R1279P depolarizes resting membrane potential, decreases current threshold, and increases firing frequency of evoked action potentials within small DRG neurons. The populations of spontaneously firing and repetitively firing neurons were increased by expressing R1279P. These observations indicate that the dominant proexcitatory gating changes associated with this mutation, including depolarized steady-state fast-, slow-, and closed-state inactivation, faster repriming, and larger ramp currents, override the depolarizing shift of activation, to produce hyperexcitability and spontaneous firing of nociceptive neurons that underlie pain. Copyright © 2014 the authors 0270-6474/14/3412328-13$15.00/0.

Substance P Depolarizes Lamprey Spinal Cord Neurons by Inhibiting Background Potassium Channels.

PubMed

Thörn Pérez, Carolina; Hill, Russell H; Grillner, Sten

2015-01-01

Substance P is endogenously released in the adult lamprey spinal cord and accelerates the burst frequency of fictive locomotion. This is achieved by multiple effects on interneurons and motoneurons, including an attenuation of calcium currents, potentiation of NMDA currents and reduction of the reciprocal inhibition. While substance P also depolarizes spinal cord neurons, the underlying mechanism has not been resolved. Here we show that effects of substance P on background K+ channels are the main source for this depolarization. Hyperpolarizing steps induced inward currents during whole-cell voltage clamp that were reduced by substance P. These background K+ channels are pH sensitive and are selectively blocked by anandamide and AVE1231. These blockers counteracted the effect of substance P on these channels and the resting membrane potential depolarization in spinal cord neurons. Thus, we have shown now that substance P inhibits background K+ channels that in turn induce depolarization, which is likely to contribute to the frequency increase observed with substance P during fictive locomotion.

Substance P Depolarizes Lamprey Spinal Cord Neurons by Inhibiting Background Potassium Channels

PubMed Central

Thörn Pérez, Carolina; Hill, Russell H.; Grillner, Sten

2015-01-01

Substance P is endogenously released in the adult lamprey spinal cord and accelerates the burst frequency of fictive locomotion. This is achieved by multiple effects on interneurons and motoneurons, including an attenuation of calcium currents, potentiation of NMDA currents and reduction of the reciprocal inhibition. While substance P also depolarizes spinal cord neurons, the underlying mechanism has not been resolved. Here we show that effects of substance P on background K+ channels are the main source for this depolarization. Hyperpolarizing steps induced inward currents during whole-cell voltage clamp that were reduced by substance P. These background K+ channels are pH sensitive and are selectively blocked by anandamide and AVE1231. These blockers counteracted the effect of substance P on these channels and the resting membrane potential depolarization in spinal cord neurons. Thus, we have shown now that substance P inhibits background K+ channels that in turn induce depolarization, which is likely to contribute to the frequency increase observed with substance P during fictive locomotion. PMID:26197458

Correlates of spreading depolarization in human scalp electroencephalography

PubMed Central

Drenckhahn, Christoph; Winkler, Maren K. L.; Major, Sebastian; Scheel, Michael; Kang, Eun-Jeung; Pinczolits, Alexandra; Grozea, Cristian; Hartings, Jed A.; Woitzik, Johannes

2012-01-01

It has been known for decades that suppression of spontaneous scalp electroencephalographic activity occurs during ischaemia. Trend analysis for such suppression was found useful for intraoperative monitoring during carotid endarterectomy, or as a screening tool to detect delayed cerebral ischaemia after aneurismal subarachnoid haemorrhage. Nevertheless, pathogenesis of such suppression of activity has remained unclear. In five patients with aneurismal subarachnoid haemorrhage and four patients with decompressive hemicraniectomy after malignant hemispheric stroke due to middle cerebral artery occlusion, we here performed simultaneously full-band direct and alternating current electroencephalography at the scalp and direct and alternating current electrocorticography at the cortical surface. After subarachnoid haemorrhage, 275 slow potential changes, identifying spreading depolarizations, were recorded electrocorticographically over 694 h. Visual inspection of time-compressed scalp electroencephalography identified 193 (70.2%) slow potential changes [amplitude: −272 (−174, −375) µV (median quartiles), duration: 5.4 (4.0, 7.1) min, electrocorticography–electroencephalography delay: 1.8 (0.8, 3.5) min]. Intervals between successive spreading depolarizations were significantly shorter for depolarizations with electroencephalographically identified slow potential change [33.0 (27.0, 76.5) versus 53.0 (28.0, 130.5) min, P = 0.009]. Electroencephalography was thus more likely to display slow potential changes of clustered than isolated spreading depolarizations. In contrast to electrocorticography, no spread of electroencephalographic slow potential changes was seen, presumably due to superposition of volume-conducted electroencephalographic signals from widespread cortical generators. In two of five patients with subarachnoid haemorrhage, serial magnetic resonance imaging revealed large delayed infarcts at the recording site, while electrocorticography showed clusters of spreading depolarizations with persistent depression of spontaneous activity. Alternating current electroencephalography similarly displayed persistent depression of spontaneous activity, and direct current electroencephalography slow potential changes riding on a shallow negative ultraslow potential. Isolated spreading depolarizations with depression of both spontaneous electrocorticographic and electroencephalographic activity displayed significantly longer intervals between successive spreading depolarizations than isolated depolarizations with only depression of electrocorticographic activity [44.0 (28.0, 132.0) min, n = 96, versus 30.0 (26.5, 51.5) min, n = 109, P = 0.001]. This suggests fusion of electroencephalographic depression periods at high depolarization frequency. No propagation of electroencephalographic depression was seen between scalp electrodes. Durations/magnitudes of isolated electroencephalographic and corresponding electrocorticographic depression periods correlated significantly. Fewer spreading depolarizations were recorded in patients with malignant hemispheric stroke but characteristics were similar to those after subarachnoid haemorrhage. In conclusion, spreading depolarizations and depressions of spontaneous activity display correlates in time-compressed human scalp direct and alternating current electroencephalography that may serve for their non-invasive detection. PMID:22366798

Large plasma-membrane depolarization precedes rapid blue-light-induced growth inhibition in cucumber

NASA Technical Reports Server (NTRS)

Spalding, E. P.; Cosgrove, D. J.

1989-01-01

Blue-light (BL)-induced suppression of elongation of etiolated Cucumis sativus L. hypocotyls began after a 30-s lag time, which was halved by increasing the fluence rate from 10 to 100 micromoles m-2 s-1. Prior to the growth suppression, the plasma-membrane of the irradiated cells depolarized by as much as 100 mV, then returned within 2-3 min to near its initial value. The potential difference measured with surface electrodes changed with an identical time course but opposite polarity. The lag time for the change in surface potential showed an inverse dependence on fluence rate, similar to the lag for the growth inhibition. Green light and red light caused neither the electrical response nor the rapid inhibition of growth. The depolarization by BL did not propagate to nonirradiated regions and exhibited a refractory period of about 10 min following a BL pulse. Fluence-response relationships for the electrical and growth responses provide correlational evidence that the plasma-membrane depolarization reflects an event in the transduction chain of this light-growth response.

Failure of feedback as a putative common mechanism of spreading depolarizations in migraine and stroke

NASA Astrophysics Data System (ADS)

Dahlem, Markus A.; Schneider, Felix M.; Schöll, Eckehard

2008-06-01

The stability of cortical function depends critically on proper regulation. Under conditions of migraine and stroke a breakdown of transmembrane chemical gradients can spread through cortical tissue. A concomitant component of this emergent spatio-temporal pattern is a depolarization of cells detected as slow voltage variations. The propagation velocity of ˜3mm/min indicates a contribution of diffusion. We propose a mechanism for spreading depolarizations (SD) that rests upon a nonlocal or noninstantaneous feedback in a reaction-diffusion system. Depending upon the characteristic space and time scales of the feedback, the propagation of cortical SD can be suppressed by shifting the bifurcation line, which separates the parameter regime of pulse propagation from the regime where a local disturbance dies out. The optimization of this feedback is elaborated for different control schemes and ranges of control parameters.

Inactivation of A currents and A channels on rat nodose neurons in culture

PubMed Central

1989-01-01

Cultured sensory neurons from nodose ganglia were investigated with whole-cell patch-clamp techniques and single-channel recordings to characterize the A current. Membrane depolarization from -40 mV holding potential activated the delayed rectifier current (IK) at potentials positive to -30 mV; this current had a sigmoidal time course and showed little or no inactivation. In most neurons, the A current was completely inactivated at the -40 mV holding potential and required hyperpolarization to remove the inactivation; the A current was isolated by subtracting the IK evoked by depolarizations from -40 mV from the total outward current evoked by depolarizations from -90 mV. The decay of the A current on several neurons had complex kinetics and was fit by the sum of three exponentials whose time constants were 10- 40 ms, 100-350 ms, and 1-3 s. At the single-channel level we found that one class of channel underlies the A current. The conductance of A channels varied with the square root of the external K concentration: it was 22 pS when exposed to 5.4 mM K externally, the increased to 40 pS when exposed to 140 mM K externally. A channels activated rapidly upon depolarization and the latency to first opening decreased with depolarization. The open time distributions followed a single exponential and the mean open time increased with depolarization. A channels inactivate in three different modes: some A channels inactivated with little reopening and gave rise to ensemble averages that decayed in 10-40 ms; other A channels opened and closed three to four times before inactivating and gave rise to ensemble averages that decayed in 100-350 ms; still other A channels opened and closed several hundred times and required seconds to inactivate. Channels gating in all three modes contributed to the macroscopic A current from the whole cell, but their relative contribution differed among neurons. In addition, A channels could go directly from the closed, or resting, state to the inactivated state without opening, and the probability for channels inactivating in this way was greater at less depolarized voltages. In addition, a few A channels appeared to go reversibly from a mode where inactivation occurred rapidly to a slow mode of inactivation. PMID:2592953

Muscle Contraction during Hyperpolarizing Currents in the Crab

PubMed Central

Uchitel, O. D.; García, H.

1974-01-01

Isolated muscle fibers from the motor legs of the crab Trichodactilus dilocarcinus were submitted to strong hyperpolarizing currents of varied intensities which produced tension during the current pulse. Threshold for tension was obtained with intensities of about 0.2 x 10–5 A, changing Em to ca. –150 mV (starting from a resting potential ofca. –80 mV). At the closure of the anodic square pulse, a second phase of tension usually appeared superimposed upon the one obtained during hyperpolarization. The first phase of tension increased with the increase of Ca++ concentration in the bath. Sr++ produced the same type of mechanical output as Ca++. When added to the normal Ca++ concentration, Ba++ and Mn++ in low concentrations (up to 21.5 mM) also increased the tension of this phase, but at higher concentrations they blocked both phases while Mg++ did not alter the tension. Of all the divalent cations employed, only Sr++ is capable of developing tension as a substitute for Ca++ in the external media. Procaine administered in a dosage (5 x 10–3 W/V)which would suppress the contracture due to caffeine (10 mM), did not modify the tension developed during the hyperpolarization. The preceding data indicate that the Ca++ required for tension during hyperpolarization comes from sites which would differ from those usually postulated for tension due to depolarization in the muscle fibers of other crustaceans (American crayfish). Furthermore, the external source of Ca++ appears to be one mainly implicated in the induction of tension due to inward current pulses. PMID:4810206

Muscle contraction during hyperpolarizing currents in the crab.

PubMed

Uchitel, O D; García, H

1974-01-01

Isolated muscle fibers from the motor legs of the crab Trichodactilus dilocarcinus were submitted to strong hyperpolarizing currents of varied intensities which produced tension during the current pulse. Threshold for tension was obtained with intensities of about 0.2 x 10(-5) A, changing E(m) to ca. -150 mV (starting from a resting potential ofca. -80 mV). At the closure of the anodic square pulse, a second phase of tension usually appeared superimposed upon the one obtained during hyperpolarization. The first phase of tension increased with the increase of Ca(++) concentration in the bath. Sr(++) produced the same type of mechanical output as Ca(++). When added to the normal Ca(++) concentration, Ba(++) and Mn(++) in low concentrations (up to 21.5 mM) also increased the tension of this phase, but at higher concentrations they blocked both phases while Mg(++) did not alter the tension. Of all the divalent cations employed, only Sr(++) is capable of developing tension as a substitute for Ca(++) in the external media. Procaine administered in a dosage (5 x 10(-3) W/V)which would suppress the contracture due to caffeine (10 mM), did not modify the tension developed during the hyperpolarization. The preceding data indicate that the Ca(++) required for tension during hyperpolarization comes from sites which would differ from those usually postulated for tension due to depolarization in the muscle fibers of other crustaceans (American crayfish). Furthermore, the external source of Ca(++) appears to be one mainly implicated in the induction of tension due to inward current pulses.

Biophysical characterization and functional consequences of a slowly inactivating potassium current in neostriatal neurons.

PubMed

Gabel, L A; Nisenbaum, E S

1998-04-01

Neostriatal spiny projection neurons can display a pronounced delay in their transition to action potential discharge that is mediated by a slowly developing ramp depolarization. The possible contribution of a slowly inactivating A-type K+ current (IAs) to this delayed excitation was investigated by studying the biophysical and functional properties of IAs using whole cell voltage- and current-clamp recording from acutely isolated neostriatal neurons. Isolation of IAs from other voltage-gated, calcium-independent K+ currents was achieved through selective blockade of IAs with low concentrations (10 microM) of the benzazepine derivative, 6-chloro-7,8-dihydroxy-3-allyl- 1-phenyl-2,3,4,5-tetra-hydro-1H-3-benzazepine (APB; SKF82958) and subsequent current subtraction. Examination of the voltage dependence of activation showed that IAs began to flow at approximately -60 mV in response to depolarization. The voltage dependence of inactivation revealed that approximately 50% of IAs channels were available at the normal resting potential (-80 mV) of these cells, but that only 20% of the channels were available at membrane potentials corresponding to spike threshold (about -40 mV). At these depolarized membrane potentials, the rate of activation was moderately rapid (tau approximately 60 ms), whereas the rate of inactivation was slow (tau approximately 1.5 s). The time course of removal of inactivation of IAs at -80 mV also was relatively slow (tau approximately 1.0 s). The subthreshold availability of IAs combined with its rapid activation and slow inactivation rates suggested that this current should be capable of dampening the onset of prolonged depolarizing responses, but over time its efficacy should diminish, slowly permitting the membrane to depolarize toward spike threshold. Voltage recording experiments confirmed this hypothesis by demonstrating that application of APB at a concentration (10 microM) that selectively blocks IAs substantially decreased the latency to discharge and increased the frequency of firing of neostriatal neurons. The properties of IAs suggest that it should play a critical role in placing the voltage limits on the recurring episodes of subthreshold depolarization which are characteristic of spiny neurons recorded in vivo. However, the voltage dependence and recovery kinetics of inactivation of IAs predict that its effectiveness will vary exponentially with the level and duration of hyperpolarization which precedes depolarizing episodes. Thus long periods of hyperpolarization should increase the availability of IAs and dampen succeeding depolarizations; whereas brief epochs of hyperpolarization should not sufficiently remove inactivation of IAs, thereby reducing its ability to limit subsequent depolarizing responses.

The muscarinic inhibition of the potassium M-current modulates the action-potential discharge in the vestibular primary-afferent neurons of the rat.

PubMed

Pérez, C; Limón, A; Vega, R; Soto, E

2009-02-18

There is consensus that muscarinic and nicotinic receptors expressed in vestibular hair cells and afferent neurons are involved in the efferent modulation of the electrical activity of the afferent neurons. However the underlying mechanisms of postsynaptic control in neurons are not well understood. In our work we show that the activation of muscarinic receptors in the vestibular neurons modulates the potassium M-current modifying the activity of afferent neurons. Whole-cell patch-clamp recordings were made on vestibular-afferent neurons isolated from Wistar rats (postnatal days 7-10) and held in primary culture (18-24 h). The M-current was studied during its deactivation after depolarizing voltage-clamp pulses. In 68% of the cells studied, those of larger capacitance, the M-current antagonists linopirdine and XE-991 reduced the amplitude of the M-current by 54%+/-7% and 50%+/-3%. The muscarinic-receptor agonist oxotremorine-M also significantly reduced the M-current by 58%+/-12% in the cells. The action of oxotremorine-M was blocked by atropine, thus indicating its cholinergic nature. The erg-channel blocker E-4031 did not significantly modify the M-current amplitude. In current-clamp experiments, linopirdine, XE-991, and oxotremorine-M modified the discharge response to current pulses from single spike to multiple spiking, reducing the adaptation of the electrical discharge. Our results indicate that large soma-size cultured vestibular-afferent neurons (most probably calyx-bearing neurons) express the M-current and that the modulation of this current by activation of muscarinic-receptor reduces its spike-frequency adaptation.

Pharmacological and anatomical separation of calcium currents in rat dentate granule neurones in vitro.

PubMed Central

Blaxter, T J; Carlen, P L; Niesen, C

1989-01-01

1. Rat dentate granule neurones in hippocampal slices were voltage-clamped at 21-23 degrees C using CsCl-filled microelectrodes. The perfusate contained TTX and K+ channel blockers to isolate pharmacologically inward Ca2+ currents. 2. From hyperpolarized holding potentials of -65 to -85 mV, depolarizing test potentials to between -50 and -40 mV elicited a transient (100-200 ms) low-threshold (TLT) current which was also elicited from more depolarized holding potentials following hyperpolarizing voltage steps of -40 mV or greater. 3. Larger depolarizing steps from a hyperpolarized holding potential triggered a large (2-6 nA), transient high-threshold (THT) inward current, rapidly peaking and decaying over 500 ms, followed by a sustained inward current component. 4. At depolarized holding potentials (-50 to -20 mV), the THT current was apparently inactivated and a sustained high-threshold (SHT) inward current was evident during depolarizing voltage steps of 10 mV or more. 5. From hyperpolarized holding potentials with depolarizing voltage steps of 10-30 mV, most neurones demonstrated a small-amplitude, sustained low-threshold (SLT) inward current with similar characteristics to the SHT current. 6. Zero-Ca2+ perfusate or high concentrations of Ca2+ channel blockers (Cd2+, Mn2+ or Ni2+) diminished or abolished all inward currents. 7. Repetitive voltage step activation of each current at 0.5 Hz reduced the large THT current to less than 25% of an unconditioned control current, reduced the SHT current by 50%, but had little effect on the TLT current. 8. A low concentration of Cd2+ (50 microM) blocked the THT and SHT currents with little effect on the TLT current. Nimodipine (1 microM) attenuated the SHT current. Ni2+ (100 microM) selectively attenuated the TLT current. 9. In low-Ca2+ perfusate, high concentrations of Ca2+ (10-15 mM), focally applied to different parts of the neurone, increased the THT current when applied to the dendrites, the SHT current when applied to the soma and the TLT current at all locations. Conversely, in regular perfusate, Cd2+ (1-5 mM), focally applied to the dendrites decreased the THT current and somatic applications decreased the SHT current. The TLT current was diminished regardless of the site of Cd2+ application. 10. These results suggest the existence of three different Ca2+ currents in dentate granule cells separable by their activation and inactivation characteristics, pharmacology and site of initiation. PMID:2557433

Modeling-independent elucidation of inactivation pathways in recombinant and native A-type Kv channels.

PubMed

Fineberg, Jeffrey D; Ritter, David M; Covarrubias, Manuel

2012-11-01

A-type voltage-gated K(+) (Kv) channels self-regulate their activity by inactivating directly from the open state (open-state inactivation [OSI]) or by inactivating before they open (closed-state inactivation [CSI]). To determine the inactivation pathways, it is often necessary to apply several pulse protocols, pore blockers, single-channel recording, and kinetic modeling. However, intrinsic hurdles may preclude the standardized application of these methods. Here, we implemented a simple method inspired by earlier studies of Na(+) channels to analyze macroscopic inactivation and conclusively deduce the pathways of inactivation of recombinant and native A-type Kv channels. We investigated two distinct A-type Kv channels expressed heterologously (Kv3.4 and Kv4.2 with accessory subunits) and their native counterparts in dorsal root ganglion and cerebellar granule neurons. This approach applies two conventional pulse protocols to examine inactivation induced by (a) a simple step (single-pulse inactivation) and (b) a conditioning step (double-pulse inactivation). Consistent with OSI, the rate of Kv3.4 inactivation (i.e., the negative first derivative of double-pulse inactivation) precisely superimposes on the profile of the Kv3.4 current evoked by a single pulse because the channels must open to inactivate. In contrast, the rate of Kv4.2 inactivation is asynchronous, already changing at earlier times relative to the profile of the Kv4.2 current evoked by a single pulse. Thus, Kv4.2 inactivation occurs uncoupled from channel opening, indicating CSI. Furthermore, the inactivation time constant versus voltage relation of Kv3.4 decreases monotonically with depolarization and levels off, whereas that of Kv4.2 exhibits a J-shape profile. We also manipulated the inactivation phenotype by changing the subunit composition and show how CSI and CSI combined with OSI might affect spiking properties in a full computational model of the hippocampal CA1 neuron. This work unambiguously elucidates contrasting inactivation pathways in neuronal A-type Kv channels and demonstrates how distinct pathways might impact neurophysiological activity.

Removal of spike frequency adaptation via neuromodulation intrinsic to the Tritonia escape swim central pattern generator.

PubMed

Katz, P S; Frost, W N

1997-10-15

For the mollusc Tritonia diomedea to generate its escape swim motor pattern, interneuron C2, a crucial member of the central pattern generator (CPG) for this rhythmic behavior, must fire repetitive bursts of action potentials. Yet, before swimming, repeated depolarizing current pulses injected into C2 at periods similar those in the swim motor program are incapable of mimicking the firing rate attained by C2 on each cycle of a swim motor program. This resting level of C2 inexcitability is attributable to its own inherent spike frequency adaptation (SFA). Clearly, this property must be altered for the swim behavior to occur. The pathway for initiation of the swimming behavior involves activation of the serotonergic dorsal swim interneurons (DSIs), which are also intrinsic members of the swim CPG. Physiologically appropriate DSI stimulation transiently decreases C2 SFA, allowing C2 to fire at higher rates even when repeatedly depolarized at short intervals. The increased C2 excitability caused by DSI stimulation is mimicked and occluded by serotonin application. Furthermore, the change in excitability is not caused by the depolarization associated with DSI stimulation or serotonin application but is correlated with a decrease in C2 spike afterhyperpolarization. This suggests that the DSIs use serotonin to evoke a neuromodulatory action on a conductance in C2 that regulates its firing rate. This modulatory action of one CPG neuron on another is likely to play a role in configuring the swim circuit into its rhythmic pattern-generating mode and maintaining it in that state.

Ischemia-induced spreading depolarization in the retina

PubMed Central

Srienc, Anja I; Biesecker, Kyle R; Shimoda, Angela M; Kur, Joanna

2016-01-01

Cortical spreading depolarization is a metabolically costly phenomenon that affects the brain in both health and disease. Following severe stroke, subarachnoid hemorrhage, or traumatic brain injury, cortical spreading depolarization exacerbates tissue damage and enlarges infarct volumes. It is not known, however, whether spreading depolarization also occurs in the retina in vivo. We report now that spreading depolarization episodes are generated in the in vivo rat retina following retinal vessel occlusion produced by photothrombosis. The properties of retinal spreading depolarization are similar to those of cortical spreading depolarization. Retinal spreading depolarization waves propagate at a velocity of 3.0 ± 0.1 mm/min and are associated with a negative shift in direct current potential, a transient cessation of neuronal spiking, arteriole constriction, and a decrease in tissue O2 tension. The frequency of retinal spreading depolarization generation in vivo is reduced by administration of the NMDA antagonist MK-801 and the 5-HT(1D) agonist sumatriptan. Branch retinal vein occlusion is a leading cause of vision loss from vascular disease. Our results suggest that retinal spreading depolarization could contribute to retinal damage in acute retinal ischemia and demonstrate that pharmacological agents can reduce retinal spreading depolarization frequency after retinal vessel occlusion. Blocking retinal spreading depolarization generation may represent a therapeutic strategy for preserving vision in branch retinal vein occlusion patients. PMID:27389181

Neuroprotective effect of cathodal transcranial direct current stimulation in a rat stroke model.

PubMed

Notturno, Francesca; Pace, Marta; Zappasodi, Filippo; Cam, Etrugul; Bassetti, Claudio L; Uncini, Antonino

2014-07-15

Experimental focal brain ischemia generates in the penumbra recurrent depolarizations which spread across the injured cortex inducing infarct growth. Transcranial direct current stimulation can induce a lasting, polarity-specific, modulation of cortical excitability. To verify whether cathodal transcranial direct current stimulation could reduce the infarct size and the number of depolarizations, focal ischemia was induced in the rat by the 3 vessels occlusion technique. In the first experiment 12 ischemic rats received cathodal stimulation (alternating 15 min on and 15 min off) starting 45 min after middle cerebral artery occlusion and lasting 4 h. In the second experiment 12 ischemic rats received cathodal transcranial direct current stimulation with the same protocol but starting soon after middle cerebral artery occlusion and lasting 6 h. In both experiments controls were 12 ischemic rats not receiving stimulation. Cathodal stimulation reduced the infarct volume in the first experiment by 20% (p=0.002) and in the second by 30% (p=0.003). The area of cerebral infarction was smaller in animals receiving cathodal stimulation in both experiments (p=0.005). Cathodal stimulation reduced the number of depolarizations (p=0.023) and infarct volume correlated with the number of depolarizations (p=0.048). Our findings indicate that cathodal transcranial direct current stimulation exert a neuroprotective effect in the acute phase of stroke possibly decreasing the number of spreading depolarizations. These findings may have translational relevance and open a new avenue in neuroprotection of stroke in humans. Copyright © 2014. Published by Elsevier B.V.

The polarized electron beam at ELSA

NASA Astrophysics Data System (ADS)

Hoffmann, M.; Drachenfels, W. V.; Frommberger, F.; Gowin, M.; Helbing, K.; Hillert, W.; Husmann, D.; Keil, J.; Michel, T.; Naumann, J.; Speckner, T.; Zeitler, G.

2001-06-01

The future medium energy physics program at the electron stretcher accelerator ELSA of Bonn University mainly relies on experiments using polarized electrons in the energy range from 1 to 3.2 GeV. To provide a polarized beam with high polarization and sufficient intensity a dedicated source has been developed and set into operation. To prevent depolarization during acceleration in the circular accelerators several depolarizing resonances have to be corrected for. Intrinsic resonances are compensated using two pulsed betatron tune jump quadrupoles. The influence of imperfection resonances is successfully reduced applying a dynamic closed orbit correction in combination with an empirical harmonic correction on the energy ramp. In order to minimize beam depolarization, both types of resonances and the correction techniques have been studied in detail. It turned out that the polarization in ELSA can be conserved up to 2.5 GeV and partially up to 3.2 GeV which is demonstrated by measurements using a Møller polarimeter installed in the external GDH1-beamline. .

[Fundamentals and Clinical Applications of Transcranial Magnetic Stimulation in Neuropsychiatry].

PubMed

Malavera, Mayra; Silva, Federico; García, Ronald; Rueda, Ligia; Carrillo, Sandra

2014-03-01

Transcranial Magnetic Stimulation (TMS) is a non-invasive method for stimulation of brain that is based on the ability of a generated magnetic field to penetrate skull and brain meninges, inducing an electric current in the brain tissues that produces neuronal depolarization. TMS can be applied as single pulse of stimulation, pairs of stimuli separated by variable intervals to the same or different brain areas, or as trains of repetitive stimuli at various frequencies. Its mechanism of action is currently unknown. Repetitive TMS can modify the excitability of the cerebral cortex, and has been postulated as a diagnostic and therapeutic tool in the area of neuropsychiatry. The aim of this article is to review the knowledge of the TMS as regards its basic principles, pathophysiological mechanism, and its usefulness in clinical practice. Copyright © 2014 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Origin and voltage dependence of asparagine-induced depolarization in intestinal cells of Xenopus embryo.

PubMed Central

Bergman, C; Bergman, J

1985-01-01

The kinetics and voltage dependence of asparagine (Asn)-induced depolarization in endoderm cells from Xenopus laevis embryos were analysed using current-clamp techniques. The depolarization is assumed to reflect the activation of an amino acid membrane carrier; it is accompanied by a slight increase in membrane resistance and cannot be explained by only the electrogenic character of the Asn carrier. It is proposed that the Asn depolarization arises, at least in part, from the decrease of the permeability ratio PK/PNa indirectly associated with the Na-coupled amino acid uptake. At room temperature (20-23 degrees C) the Asn response develops according to a single exponential function whose time constant is correlated with the final level of depolarization. Both amplitude and rise time of the depolarization are sensitive to variations of membrane potential and changes in Asn or Na external concentrations. Lowering the temperature decreases the amplitude of the Asn depolarization and increases its rise time with a Q10 factor of two; the kinetics remain of the Michaelis-Menten type, with a marked decrease in delta Emax and no change in Km. When the holding potential is altered by depolarizing and hyperpolarizing currents, the Asn response varies according to a bell-shaped characteristic presenting an optimum near the normal resting level. Membrane depolarizations induced by Na/K-pump inhibitors or high external K concentrations reduce the size of the Asn response; repolarizing the cell by current injection does not reverse the inhibitory effect of external K ions. Hyperpolarizing the membrane with a K-free Ringer solution increases the amplitude of the Asn response. In all these cases a decrease in delta Emax accounts for the apparent voltage sensitivity of the carrier mechanism. When induced by alterations of [K]o, an additional change in Km is observed, suggesting a K/Na-competitive inhibition of the Asn carrier. The results are discussed in terms of the amino acid carrier and passive membrane properties. It is suggested that the outward K-electrochemical gradient contributes an additional source of energy to the Na-dependent Asn uptake. PMID:4057089

[Cortical spreading depolarization: a new pathophysiological mechanism in neurological diseases].

PubMed

Sánchez-Porras, Renán; Robles-Cabrera, Adriana; Santos, Edgar

2014-05-20

Cortical spreading depolarization is a wave of almost complete depolarization of the neuronal and glial cells that occurs in different neurological diseases such as migraine with aura, subarachnoid hemorrhage, intracerebral hemorrhage, head trauma and stroke. These depolarization waves are characterized by a change in the negative potential with an amplitude between -10 and -30mV, duration of ∼1min and changes in the ion homeostasis between the intra- and extracellular space. This results in neuronal edema and dendritic distortion. Under pathologic states of hypoperfusion, cortical spreading depolarization can produce oxidative stress, worsen hypoxia and induce neuronal death. This is due to intense arterial vasoconstriction produced by an inverse response called spreading ischemia. Only in the last years there has been an electrophysiological confirmation of cortical spreading depolarization in human brains. Occurrence of cortical spreading depolarization has been associated with worse outcome in patients. Currently, increased knowledge regarding the pathophysiologic mechanisms supports the hypothetical correlation of cortical spreading depolarization with brain damage in humans. There are diverse therapeutic alternatives that promise inhibition of cortical spreading depolarization and subsequent better outcomes. Copyright © 2013 Elsevier España, S.L. All rights reserved.

The physostigmine depolarization potentiating effect of salicylate in frog skeletal muscle.

PubMed

Varga, E; Kovács, L; Szücs, G; Illés, B

1975-01-01

1) The frog's sartorius muscle was depolarized depending on the degree of concentration 2--4 times more intensely by physostigmine salicylate than by physostigmine sulphate. 2) In normal Ringer's solution, 1 mM physostigmine salicylate decreased the sensitivity of the membrane to potassium depolarization by about 90%. Under similar experimental conditions, physostigmine sulphate and Na salicylate, respectively, decrease the sensitivity of the membrane to potassium depolarization by about 30%. 3) The difference manifested in the depolarizing effect of salicylate and other physostigmine salts (chloride, sulphate, phosphate, formiate, acetate, monochloracetate, benzoate and para-oxy-benzoate) is expressed already at 1 mM concentration (about 10-fold), if the muscle had been equilibrated in chloride-free glucuronate or sulphate milieu. 4) The depolarization develops slowly. It takes 30--60 minutes for the new steady state to develop even in the superficial sartorius fibres. If depolarization has reached its maximum on an average 100 mV, the membrane potential remains unchanged for hours. 5) Depolarization ensues at an unchanged degree in the presence of Na-free (choline) Ringer as well as in the presence of 2X10(-8) g/ml tetrodotoxin; therefore, it is not a Na-dependent process. 6) Under the influence of 1 mM physostigmine salicylate the membrane's resistance to the inward potassium current increased about twofold, while the increase was only 15% to the outward potassium current. It is assumed that the salicylate anion is characteristically capable of potentiating the decreasing effect of physostigmine on potassium permeability, though the role of the metabolic effect of salicylate cannot be excluded.

Effects of haloperidol on Kv4.3 potassium channels.

PubMed

Lee, Hong Joon; Sung, Ki-Wug; Hahn, Sang June

2014-10-05

Haloperidol is commonly used in clinical practice to treat acute and chronic psychosis, but it also has been associated with adverse cardiovascular events. We investigated the effects of haloperidol on Kv4.3 currents stably expressed in CHO cells using a whole-cell patch-clamp technique. Haloperidol did not significantly inhibit the peak amplitude of Kv4.3, but accelerated the decay rate of inactivation of Kv4.3 in a concentration-dependent manner. Thus, the effects of haloperidol on Kv4.3 were estimated from the integral of the Kv4.3 currents during the depolarization pulse. The Kv4.3 was decreased by haloperidol in a concentration-dependent manner with an IC50 value of 3.6 μM. Haloperidol accelerated the decay rate of Kv4.3 inactivation and activation kinetics in a concentration-dependent manner, thereby decreasing the time-to-peak. Haloperidol shifted the voltage dependence of the steady-state activation and inactivation of Kv4.3 in a hyperpolarizing direction. Haloperidol also caused an acceleration of the closed-state inactivation of Kv4.3. Haloperidol produced a use-dependent block of Kv4.3, which was accompanied by a slowing of recovery from the inactivation of Kv4.3. These results suggest that haloperidol blocks Kv4.3 by both interacting with the open state of Kv4.3 channels during depolarization and accelerating the closed-state inactivation at subthreshold membrane potentials. Copyright © 2014 Elsevier B.V. All rights reserved.

Hyperfine-Structure-Induced Depolarization of Impulsively Aligned I2 Molecules

NASA Astrophysics Data System (ADS)

Thomas, Esben F.; Søndergaard, Anders A.; Shepperson, Benjamin; Henriksen, Niels E.; Stapelfeldt, Henrik

2018-04-01

A moderately intense 450 fs laser pulse is used to create rotational wave packets in gas phase I2 molecules. The ensuing time-dependent alignment, measured by Coulomb explosion imaging with a delayed probe pulse, exhibits the characteristic revival structures expected for rotational wave packets but also a complex nonperiodic substructure and decreasing mean alignment not observed before. A quantum mechanical model attributes the phenomena to coupling between the rotational angular momenta and the nuclear spins through the electric quadrupole interaction. The calculated alignment trace agrees very well with the experimental results.

Depolarizing Effects of Daikenchuto on Interstitial Cells of Cajal from Mouse Small Intestine

PubMed Central

Kim, Hyungwoo; Kim, Hyun Jung; Yang, Dongki; Jung, Myeong Ho; Kim, Byung Joo

2017-01-01

Background: Daikenchuto (DKT; TJ-100, TU-100), a traditional herbal medicineis used in modern medicine to treat gastrointestinal (GI) functional disorders. Interstitial cells of Cajal (ICCs) are the pacemaker cells of the GI tract and play important roles in the regulation of GI motility. Objective: The objective of this study was to investigate the effects of DKT on the pacemaker potentials (PPs) of cultured ICCs from murine small intestine. Materials and Methods: Enzymatic digestions were used to dissociate ICCs from mouse small intestine tissues. All experiments on ICCs were performed after 12 h of culture. The whole-cell patch-clamp configuration was used to record ICC PPs (current clamp mode). All experiments were performed at 30-32°C. Results: In current-clamp modeDKT depolarized and concentration-dependently decreased the amplitudes of PPs. Y25130 (a 5-HT3 receptor antagonist) or SB269970 (a 5-HT7 receptor antagonist) did not block DKT-induced PP depolarization, but RS39604 (a 5-HT4 receptor antagonist) did. Methoctramine (a muscarinic M2 receptor antagonist) failed to block DKT-induced PP depolarization, but pretreating 4-diphenylacetoxy-N-methylpiperidine methiodide (a muscarinic M3 receptor antagonist) facilitated blockade of DKT-induced PP depolarization. Pretreatment with an external Ca2+-free solution or thapsigargin abolished PPsand under these conditions, DKT did not induce PP depolarization. Furthermore Ginseng radix and Zingiberis rhizomes depolarized PPs, whereas Zanthoxyli fructus fruit (the third component of DKT) hyperpolarized PPs. Conclusion: These results suggest that DKT depolarizes ICC PPs in an internal or external Ca2+-dependent manner by stimulating 5-HT4 and M3 receptors. Furthermore, the authors suspect that the component in DKT largely responsible for depolarization is probably also a component of Ginseng radix and Zingiberis rhizomes. SUMMARY Daikenchuto (DKT) depolarized and concentration-dependently decreased the amplitudes of pacemaker potentials (PPs)Y25130 (a 5-HT3 receptor antagonist) or SB269970 (a 5-HT7 receptor antagonist) did not block DKT-induced PP depolarization, but RS39604 (a 5-HT4 receptor antagonist) didMethoctramine (a muscarinic M2 receptor antagonist) failed to block DKT-induced PP depolarization, but pretreating 4-DAMP (a muscarinic M3 receptor antagonist) facilitated blockade of DKT-induced PP depolarizationGinseng radix and Zingiberis rhizomes depolarized PPswhereas Zanthoxyli fructus fruit (the third component of DKT) hyperpolarized PPs. Abbreviation used: DKT: Daikenchuto, GI: Gastrointestinal, ICCs: Interstitial cells of Cajal, PPs: Pacemaker Potentials. PMID:28216898

Depolarizing Effects of Daikenchuto on Interstitial Cells of Cajal from Mouse Small Intestine.

PubMed

Kim, Hyungwoo; Kim, Hyun Jung; Yang, Dongki; Jung, Myeong Ho; Kim, Byung Joo

2017-01-01

Daikenchuto (DKT; TJ-100, TU-100), a traditional herbal medicineis used in modern medicine to treat gastrointestinal (GI) functional disorders. Interstitial cells of Cajal (ICCs) are the pacemaker cells of the GI tract and play important roles in the regulation of GI motility. The objective of this study was to investigate the effects of DKT on the pacemaker potentials (PPs) of cultured ICCs from murine small intestine. Enzymatic digestions were used to dissociate ICCs from mouse small intestine tissues. All experiments on ICCs were performed after 12 h of culture. The whole-cell patch-clamp configuration was used to record ICC PPs (current clamp mode). All experiments were performed at 30-32°C. In current-clamp modeDKT depolarized and concentration-dependently decreased the amplitudes of PPs. Y25130 (a 5-HT 3 receptor antagonist) or SB269970 (a 5-HT 7 receptor antagonist) did not block DKT-induced PP depolarization, but RS39604 (a 5-HT 4 receptor antagonist) did. Methoctramine (a muscarinic M 2 receptor antagonist) failed to block DKT-induced PP depolarization, but pretreating 4-diphenylacetoxy-N-methylpiperidine methiodide (a muscarinic M 3 receptor antagonist) facilitated blockade of DKT-induced PP depolarization. Pretreatment with an external Ca 2+ -free solution or thapsigargin abolished PPsand under these conditions, DKT did not induce PP depolarization. Furthermore Ginseng radix and Zingiberis rhizomes depolarized PPs, whereas Zanthoxyli fructus fruit (the third component of DKT) hyperpolarized PPs. These results suggest that DKT depolarizes ICC PPs in an internal or external Ca 2+ -dependent manner by stimulating 5-HT 4 and M 3 receptors. Furthermore, the authors suspect that the component in DKT largely responsible for depolarization is probably also a component of Ginseng radix and Zingiberis rhizomes. Daikenchuto (DKT) depolarized and concentration-dependently decreased the amplitudes of pacemaker potentials (PPs)Y25130 (a 5-HT 3 receptor antagonist) or SB269970 (a 5-HT 7 receptor antagonist) did not block DKT-induced PP depolarization, but RS39604 (a 5-HT 4 receptor antagonist) didMethoctramine (a muscarinic M 2 receptor antagonist) failed to block DKT-induced PP depolarization, but pretreating 4-DAMP (a muscarinic M 3 receptor antagonist) facilitated blockade of DKT-induced PP depolarizationGinseng radix and Zingiberis rhizomes depolarized PPswhereas Zanthoxyli fructus fruit (the third component of DKT) hyperpolarized PPs. Abbreviation used: DKT: Daikenchuto, GI: Gastrointestinal, ICCs: Interstitial cells of Cajal, PPs: Pacemaker Potentials.

Effect of extracellular ATP on contraction, cytosolic calcium activity, membrane voltage and ion currents of rat mesangial cells in primary culture.

PubMed Central

Pavenstädt, H.; Gloy, J.; Leipziger, J.; Klär, B.; Pfeilschifter, J.; Schollmeyer, P.; Greger, R.

1993-01-01

1. The effects of extracellular ATP on contraction, membrane voltage (Vm), ion currents and intracellular calcium activity [Ca2+]i were studied in rat mesangial cells (MC) in primary culture. 2. Addition of extracellular ATP (10(-5) and 10(-4) M) to MC led to a cell contraction which was independent of extracellular calcium. 3. Membrane voltage (Vm) and ion currents were measured with the nystatin patch clamp technique. ATP induced a concentration-dependent transient depolarization of Vm (ED50: 2 x 10(-6) M). During the transient depolarization ion currents were monitored simultaneously and showed an increase of the inward- and outward current. 4. In a buffer with a reduced extracellular chloride concentration (from 145 to 30 mM) ATP induced a depolarization augmented to -4 +/- 4 mV. 5. ATP-gamma-S and 2-methylthio-ATP depolarized Vm to the same extent as ATP, whereas alpha,beta-methylene-ATP (all 10(-5) M) had no effect on Vm. 6. The Ca2+ ionophore, A23187, depolarized Vm transiently from -51 +/- 2 to -28 +/- 4 mV and caused an increase of the inward current. 7. The intracellular calcium activity [Ca2+]i was measured with the fura-2 technique. ATP stimulated a concentration-dependent increase of [Ca2+]i (ED50: 5 x 10(-6) M). The increase of [Ca2+]i was biphasic with an initial peak followed by a sustained plateau. 8. The [Ca2+]i peak was still present in an extracellular Ca(2+)-free buffer, whereas the plateau was abolished. Verapamil (10(-4) M) did not inhibit the [Ca2+]i increase induced by ATP.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 1 PMID:7691366

Simultaneous measurements of magnesium, calcium and sodium influxes in perfused squid giant axons under membrane potential control.

PubMed

Rojas, E; Taylor, R E

1975-10-01

1. Giant axons from the squids Dosidicus gigas, Loligo forbesi and Loligo vulgaris were internally perfused with 550 or 275 mM KF plus sucrose and bathed in artificial sea water containing 45Ca, 28Mg or mixtures of 45Ca-28Mg or 45Ca-22Na. Resting influxes and extra influxes during voltage-clamp pulses were measured by collecting and counting the internal perfusate. 2. For Dosidicus axons in 10 mM-CaCl2 the resting influx of calcium was 0-016 +/- 0-007 p-mole/cm2 sec and a linear function of external concentration. For two experiments in 10 and 84-7 mM-CaCl2, 100 nM tetrodotoxin had no effect. Resting calcium influx in 10 mM-CaCl2 was 0-017 +/- 0-013 p-mole/cm2 sec for Loligo axons. 3. With 55 mM-MgCl2 outside the average resting magnesium influx was 0-124 +/- 0-080 p-mole/cm2 sec for Loligo axons. Discarding one aberrant point the value is 0-105 +/- 0-046 which is not significantly different from the resting calcium influx for Dosidicus fibres in 55 mM-CaCl2, given as 0-094 p-mole/cm2 sec by the regression line shown in Fig. 1. In two experiments 150 nM tetrodotoxin had no effect. 4. With 430 mM-NaCl outside 100 nM tetrodotoxin reduced the average resting influx of sodium in Dosidicus axon from 27-7 +/- 4-5 to 25-1 +/- 6-2 p-mole/cm2 sec and for Loligo fibres in 460 mM-NaCl from 50-5 +/- 4 to 20 +/- 8 p-mole/cm2 sec. 5. Using depolarizing pulses of various durations, the extra calcium influx occurred in two phases. The early phase was eliminated by external application of tetrodotoxin. The results of analysis are consistent with, but do not rigorously demonstrate, the conclusion that the tetrodotoxin sensitive calcium entry is flowing through the normal sodium channels (cf. Baker, Hodgkin & Ridgway, 1971). 6. Measurements of extra influxes using 22Na and 45Ca simultaneously indicate that the time courses of tetrodotoxin sensitive calcium and sodium entry are similar but not necessarily identical. It is very doubtful that any significant calcium entry occurs before the sodium or is involved in the activation of the sodium system. 7. These measurements confirm for Loligo, as previously shown for Dosidicus axons, that the magnitude and time course of the sodium entry during a depolarizing pulse deduced from electrical measurements is the same as that measured with 22Na. 8. Using 28Mg, or mixtures of 45Ca and 28Mg, we observed a single phase of magnesium entry which was insensitive to external tetrodotoxin or internal tetraethyl ammonium. The magnitude of the magnesium influx was considerably greater than the calcium extra entry and large enough to have been detected in the experiments of Meves & Vogel (1973) if it represented current. 9. We suggest the possibility that the calcium and magnesium extra influxes, after external treatment with tetrodotoxin, during a depolarizing pulse, do not contribute to the measured current.

Simultaneous measurements of magnesium, calcium and sodium influxes in perfused squid giant axons under membrane potential control.

PubMed Central

Rojas, E; Taylor, R E

1975-01-01

1. Giant axons from the squids Dosidicus gigas, Loligo forbesi and Loligo vulgaris were internally perfused with 550 or 275 mM KF plus sucrose and bathed in artificial sea water containing 45Ca, 28Mg or mixtures of 45Ca-28Mg or 45Ca-22Na. Resting influxes and extra influxes during voltage-clamp pulses were measured by collecting and counting the internal perfusate. 2. For Dosidicus axons in 10 mM-CaCl2 the resting influx of calcium was 0-016 +/- 0-007 p-mole/cm2 sec and a linear function of external concentration. For two experiments in 10 and 84-7 mM-CaCl2, 100 nM tetrodotoxin had no effect. Resting calcium influx in 10 mM-CaCl2 was 0-017 +/- 0-013 p-mole/cm2 sec for Loligo axons. 3. With 55 mM-MgCl2 outside the average resting magnesium influx was 0-124 +/- 0-080 p-mole/cm2 sec for Loligo axons. Discarding one aberrant point the value is 0-105 +/- 0-046 which is not significantly different from the resting calcium influx for Dosidicus fibres in 55 mM-CaCl2, given as 0-094 p-mole/cm2 sec by the regression line shown in Fig. 1. In two experiments 150 nM tetrodotoxin had no effect. 4. With 430 mM-NaCl outside 100 nM tetrodotoxin reduced the average resting influx of sodium in Dosidicus axon from 27-7 +/- 4-5 to 25-1 +/- 6-2 p-mole/cm2 sec and for Loligo fibres in 460 mM-NaCl from 50-5 +/- 4 to 20 +/- 8 p-mole/cm2 sec. 5. Using depolarizing pulses of various durations, the extra calcium influx occurred in two phases. The early phase was eliminated by external application of tetrodotoxin. The results of analysis are consistent with, but do not rigorously demonstrate, the conclusion that the tetrodotoxin sensitive calcium entry is flowing through the normal sodium channels (cf. Baker, Hodgkin & Ridgway, 1971). 6. Measurements of extra influxes using 22Na and 45Ca simultaneously indicate that the time courses of tetrodotoxin sensitive calcium and sodium entry are similar but not necessarily identical. It is very doubtful that any significant calcium entry occurs before the sodium or is involved in the activation of the sodium system. 7. These measurements confirm for Loligo, as previously shown for Dosidicus axons, that the magnitude and time course of the sodium entry during a depolarizing pulse deduced from electrical measurements is the same as that measured with 22Na. 8. Using 28Mg, or mixtures of 45Ca and 28Mg, we observed a single phase of magnesium entry which was insensitive to external tetrodotoxin or internal tetraethyl ammonium. The magnitude of the magnesium influx was considerably greater than the calcium extra entry and large enough to have been detected in the experiments of Meves & Vogel (1973) if it represented current. 9. We suggest the possibility that the calcium and magnesium extra influxes, after external treatment with tetrodotoxin, during a depolarizing pulse, do not contribute to the measured current. PMID:1202193

Paired-Pulse Depression at Photoreceptor Synapses

PubMed Central

Rabl, Katalin; Cadetti, Lucia; Thoreson, Wallace B.

2011-01-01

Synaptic depression produced by repetitive stimulation is likely to be particularly important in shaping responses of second-order retinal neurons at the tonically active photoreceptor synapse. We analyzed the time course and mechanisms of synaptic depression at rod and cone synapses using paired-pulse protocols involving two complementary measurements of exocytosis: (1) paired whole-cell recordings of the postsynaptic current (PSC) in second-order retinal neurons and (2) capacitance measurements of vesicular membrane fusion in rods and cones. PSCs in ON bipolar, OFF bipolar, and horizontal cells evoked by stimulation of either rods or cones recovered from paired-pulse depression (PPD) at rates similar to the recovery of exocytotic capacitance changes in rods and cones. Correlation between presynaptic and postsynaptic measures of recovery from PPD suggests that 80 –90% of the depression at these synapses is presynaptic in origin. Consistent with a predominantly presynaptic mechanism, inhibiting desensitization of postsynaptic glutamate receptors had little effect on PPD. The depression of exocytotic capacitance changes exceeded depression of the presynaptic calcium current, suggesting that it is primarily caused by a depletion of synaptic vesicles. In support of this idea, limiting Ca2+ influx by using weaker depolarizing stimuli promoted faster recovery from PPD. Although cones exhibit much faster exocytotic kinetics than rods, exocytotic capacitance changes recovered from PPD at similar rates in both cell types. Thus, depression of release is not likely to contribute to differences in the kinetics of transmission from rods and cones. PMID:16510733

Voltage- and ATP-dependent structural rearrangements of the P2X2 receptor associated with the gating of the pore

PubMed Central

Keceli, Batu; Kubo, Yoshihiro

2014-01-01

P2X2 is an extracellular ATP-gated cation channel which has a voltage-dependent gating property even though it lacks a canonical voltage sensor. It is a trimer in which each subunit has two transmembrane helices and a large extracellular domain. The three inter-subunit ATP binding sites are linked to the pore forming transmembrane (TM) domains by β-strands. We analysed structural rearrangements of the linker strands between the ATP binding site and TM domains upon ligand binding and voltage change, electrophysiologically in Xenopus oocytes, using mutants carrying engineered thiol-modifiable cysteine residues. (1) We demonstrated that the double mutant D315C&I67C (at β-14 and β-1, respectively) shows a 2- to 4-fold increase in current amplitude after treatment with a reducing reagent, dithiothreitol (DTT). Application of the thiol-reactive metal Cd2+ induced current decline due to bond formation between D315C and I67C. This effect was not observed in wild type (WT) or in single point mutants. (2) Cd2+-induced current decline was analysed in hyperpolarized and depolarized conditions with different pulse protocols, and also in the presence and absence of ATP. (3) Current decline induced by Cd2+ could be clearly observed in the presence of ATP, but was not clear in the absence of ATP, showing a state-dependent modification. (4) In the presence of ATP, Cd2+ modification was significantly faster in hyperpolarized than in depolarized conditions, showing voltage-dependent structural rearrangements of the linker strands. (5) Experiments using tandem trimeric constructs (TTCs) with controlled number and position of mutations in the trimer showed that the bridging by Cd2+ between 315 and 67 was not intra- but inter-subunit. (6) Finally, we performed similar analyses of a pore mutant T339S, which makes the channel activation voltage insensitive. Cd2+ modification rates of T339S were similar in hyperpolarized and depolarized conditions. Taking these results together, we demonstrated that structural rearrangements of the linker region of the P2X2 receptor channel are induced not only by ligand binding but also by membrane potential change. PMID:25172943

Effect of Alkali Metal Cations on Slow Inactivation of Cardiac Na+ Channels

PubMed Central

Townsend, Claire; Horn, Richard

1997-01-01

Human heart Na+ channels were expressed transiently in both mammalian cells and Xenopus oocytes, and Na+ currents measured using 150 mM intracellular Na+. The kinetics of decaying outward Na+ current in response to 1-s depolarizations in the F1485Q mutant depends on the predominant cation in the extracellular solution, suggesting an effect on slow inactivation. The decay rate is lower for the alkali metal cations Li+, Na+, K+, Rb+, and Cs+ than for the organic cations Tris, tetramethylammonium, N-methylglucamine, and choline. In whole cell recordings, raising [Na+]o from 10 to 150 mM increases the rate of recovery from slow inactivation at −140 mV, decreases the rate of slow inactivation at relatively depolarized voltages, and shifts steady-state slow inactivation in a depolarized direction. Single channel recordings of F1485Q show a decrease in the number of blank (i.e., null) records when [Na+]o is increased. Significant clustering of blank records when depolarizing at a frequency of 0.5 Hz suggests that periods of inactivity represent the sojourn of a channel in a slow-inactivated state. Examination of the single channel kinetics at +60 mV during 90-ms depolarizations shows that neither open time, closed time, nor first latency is significantly affected by [Na+]o. However raising [Na+]o decreases the duration of the last closed interval terminated by the end of the depolarization, leading to an increased number of openings at the depolarized voltage. Analysis of single channel data indicates that at a depolarized voltage a single rate constant for entry into a slow-inactivated state is reduced in high [Na+]o, suggesting that the binding of an alkali metal cation, perhaps in the ion-conducting pore, inhibits the closing of the slow inactivation gate. PMID:9234168

The relationship between Q gamma and Ca release from the sarcoplasmic reticulum in skeletal muscle

PubMed Central

1991-01-01

Asymmetric membrane currents and fluxes of Ca2+ release were determined in skeletal muscle fibers voltage clamped in a Vaseline-gap chamber. The conditioning pulse protocol 1 for suppressing Ca2+ release and the "hump" component of charge movement current (I gamma), described in the first paper of this series, was applied at different test pulse voltages. The amplitude of the current suppressed during the ON transient reached a maximum at slightly suprathreshold test voltages (- 50 to -40 mV) and decayed at higher voltages. The component of charge movement current suppressed by 20 microM tetracaine also went through a maximum at low pulse voltages. This anomalous voltage dependence is thus a property of I gamma, defined by either the conditioning protocol or the tetracaine effect. A negative (inward-going) phase was often observed in the asymmetric current during the ON of depolarizing pulses. This inward phase was shown to be an intramembranous charge movement based on (a) its presence in the records of total membrane current, (b) its voltage dependence, with a maximum at slightly suprathreshold voltages, (c) its association with a "hump" in the asymmetric current, (d) its inhibition by interventions that reduce the "hump", (e) equality of ON and OFF areas in the records of asymmetric current presenting this inward phase, and (f) its kinetic relationship with the time derivative of Ca release flux. The nonmonotonic voltage dependence of the amplitude of the hump and the possibility of an inward phase of intramembranous charge movement are used as the main criteria in the quantitative testing of a specific model. According to this model, released Ca2+ binds to negatively charged sites on the myoplasmic face of the voltage sensor and increases the local transmembrane potential, thus driving additional charge movement (the hump). This model successfully predicts the anomalous voltage dependence and all the kinetic properties of I gamma described in the previous papers. It also accounts for the inward phase in total asymmetric current and in the current suppressed by protocol 1. According to this model, I gamma accompanies activating transitions at the same set of voltage sensors as I beta. Therefore it should open additional release channels, which in turn should cause more I gamma, providing a positive feedback mechanism in the regulation of calcium release. PMID:1650812

Prevention of Ca(2+)-mediated action potentials in GABAergic local circuit neurones of rat thalamus by a transient K+ current.

PubMed Central

Pape, H C; Budde, T; Mager, R; Kisvárday, Z F

1994-01-01

1. Neurones enzymatically dissociated from the rat dorsal lateral geniculate nucleus (LGN) were identified as GABAergic local circuit interneurones and geniculocortical relay cells, based upon quantitative analysis of soma profiles, immunohistochemical detection of GABA or glutamic acid decarboxylase, and basic electrogenic behaviour. 2. During whole-cell current-clamp recording, isolated LGN neurones generated firing patterns resembling those in intact tissue, with the most striking difference relating to the presence in relay cells of a Ca2+ action potential with a low threshold of activation, capable of triggering fast spikes, and the absence of a regenerative Ca2+ response with a low threshold of activation in local circuit cells. 3. Whole-cell voltage-clamp experiments demonstrated that both classes of LGN neurones possess at least two voltage-dependent membrane currents which operate in a range of membrane potentials negative to the threshold for generation of Na(+)-K(+)-mediated spikes: the T-type Ca2+ current (IT) and an A-type K+ current (IA). Taking into account the differences in membrane surface area, the average size of IT was similar in the two types of neurones, and interneurones possessed a slightly larger A-conductance. 4. In local circuit neurones, the ranges of steady-state inactivation and activation of IT and IA were largely overlapping (VH = 81.1 vs. -82.8 mV), both currents activated at around -70 mV, and they rapidly increased in amplitude with further depolarization. In relay cells, the inactivation curve of IT was negatively shifted along the voltage axis by about 20 mV compared with that of IA (Vh = -86.1 vs. -69.2 mV), and the activation threshold for IT (at -80 mV) was 20 mV more negative than that for IA. In interneurones, the activation range of IT was shifted to values more positive than that in relay cells (Vh = -54.9 vs. -64.5 mV), whereas the activation range of IA was more negative (Vh = -25.2 vs. -14.5 mV). 5. Under whole-cell voltage-clamp conditions that allowed the combined activation of Ca2+ and K+ currents, depolarizing voltage steps from -110 mV evoked inward currents resembling IT in relay cells and small outward currents indicative of IA in local circuit neurones. After blockade of IA with 4-aminopyridine (4-AP), the same pulse protocol produced IT in both types of neurones. Under current clamp, 4-AP unmasked a regenerative membrane depolarization with a low threshold of activation capable of triggering fast spikes in local circuit neurones.(ABSTRACT TRUNCATED AT 400 WORDS) Images Figure 1 PMID:7965855

Spontaneous release from mossy fiber terminals inhibits Ni2+-sensitive T-type Ca2+ channels of CA3 pyramidal neurons in the rat organotypic hippocampal slice.

PubMed

Reid, Christopher A; Xu, Shenghong; Williams, David A

2008-01-01

Mossy fibers (axons arising from dentate granule cells) form large synaptic contacts exclusively onto the proximal apical dendrites of CA3 pyramidal neurons. They can generate large synaptic currents that occur in close proximity to the soma. These properties mean that active conductance in the proximal apical dendrite could have a disproportionate influence on CA3 pyramidal neuron excitability. Ni(2+)-sensitive T-type Ca(2+) channels are important modulators of dendritic excitability. Here, we use an optical approach to determine the contribution of Ni(2+) (100 microM)-sensitive Ca(2+) channels to action potential (AP) elicited Ca(2+) flux in the soma, proximal apical and distal apical dendrites. At resting membrane potentials Ni(2+)-sensitive Ca(2+) channels do not contribute to the Ca(2+) signal in the proximal apical dendrite, but do contribute in the other cell regions. Spontaneous release from mossy fiber terminals acting on 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)-sensitive postsynaptic channels underlies a tonic inhibition of Ni(2+)-sensitive channels. Chelating Zn(2+) with CaEDTA blocks CNQX-sensitive changes in Ca(2+) flux implicating a mechanistic role of this ion in T-type Ca(2+) channel block. To test if this inhibition influenced excitability, progressively larger depolarizing pulses were delivered to CA3 pyramidal neurons. CNQX significantly reduced the size of the depolarizing step required to generate APs and increased the absolute number of APs per depolarizing step. This change in AP firing was completely reversed by the addition of Ni(2+). This mechanism may reduce the impact of T-type Ca(2+) channels in a region where large synaptic events are common.

Computational Model of the Insect Pheromone Transduction Cascade

PubMed Central

Gu, Yuqiao; Lucas, Philippe; Rospars, Jean-Pierre

2009-01-01

A biophysical model of receptor potential generation in the male moth olfactory receptor neuron is presented. It takes into account all pre-effector processes—the translocation of pheromone molecules from air to sensillum lymph, their deactivation and interaction with the receptors, and the G-protein and effector enzyme activation—and focuses on the main post-effector processes. These processes involve the production and degradation of second messengers (IP3 and DAG), the opening and closing of a series of ionic channels (IP3-gated Ca2+ channel, DAG-gated cationic channel, Ca2+-gated Cl− channel, and Ca2+- and voltage-gated K+ channel), and Ca2+ extrusion mechanisms. The whole network is regulated by modulators (protein kinase C and Ca2+-calmodulin) that exert feedback inhibition on the effector and channels. The evolution in time of these linked chemical species and currents and the resulting membrane potentials in response to single pulse stimulation of various intensities were simulated. The unknown parameter values were fitted by comparison to the amplitude and temporal characteristics (rising and falling times) of the experimentally measured receptor potential at various pheromone doses. The model obtained captures the main features of the dose–response curves: the wide dynamic range of six decades with the same amplitudes as the experimental data, the short rising time, and the long falling time. It also reproduces the second messenger kinetics. It suggests that the two main types of depolarizing ionic channels play different roles at low and high pheromone concentrations; the DAG-gated cationic channel plays the major role for depolarization at low concentrations, and the Ca2+-gated Cl− channel plays the major role for depolarization at middle and high concentrations. Several testable predictions are proposed, and future developments are discussed. PMID:19300479

Reconstruction of ionic currents in a molluscan photoreceptor.

PubMed Central

Sakakibara, M.; Ikeno, H.; Usui, S.; Collin, C.; Alkon, D. L.

1993-01-01

Two-microelectrode voltage-clamp measurements were made to determine the kinetics and voltage dependence of ionic currents across the soma membrane of the Hermissenda type B photoreceptor. The voltage-dependent outward potassium currents, IA and ICa(2+)-K+, the inward voltage-dependent calcium current, ICa2+ and the light-induced current, IIgt, were then described with Hodgkin-Huxley-type equations. The fast-activating and inactivating potassium current, IA, was described by the equation; IA(t) = gA(max)(ma infinity[1-exp(-t/tau ma)])3 x (ha infinity [1-exp(-t/tau ha)] + exp(-t/tau ha)) (Vm-EK), where the parameters ma infinity, ha infinity, tau ma, and tau ha are functions of membrane potential, Vm, and ma infinity and ha infinity are steady-state activation and inactivation parameters. Similarly, the calcium-dependent outward potassium current, ICa(2+)-K+, was described by the equation, ICa(2+)-K+ (t) = gc(max)(mc infinity(VC)(1-exp[-t/tau mc (VC)]))pc (hc infinity(VC) [1-exp(-t/tau hc)] + exp(-t/tau hc(VC)])pc(VC-EK). In high external potassium, ICa(2+)-K+ could be measured in approximate isolation from other currents as a voltage-dependent inward tail current following a depolarizing command pulse from a holding potential of -60 mV. A voltage-dependent inward calcium current across the type B soma membrane, ICa2+, activated rapidly, showed little inactivation, and was described by the equation: ICa2+ = gCa(max) [1 + exp](-Vm-5)/7]-1 (Vm-ECa), where gCa(max) was 0.5 microS. The light-induced current with both fast and slow phases was described by: IIgt(t) = IIgt1 + IIgt2 + IIgt3, IIgti = gIgti [1-exp(- ton/tau mi)] exp(-ton/tau hi)(Vm-EIgti) (i = 1, 2). For i = 3, /Igt(t) = gigt3m33h3(Vm - Eigt3)exp(-ton/Ton) x exp(-tfoff/t Off). Based on these reconstructions of ionic currents, learning-induced enhancement of the long lasting depolarization (LLD) of the photoreceptor'slight response was shown to arise from progressive inactivation of /A, lca2+ -K+, and lCa2+. PMID:8369456

Altered ion channel conductance and ionic selectivity induced by large imposed membrane potential pulse.

PubMed Central

Chen, W; Lee, R C

1994-01-01

The effects of large magnitude transmembrane potential pulses on voltage-gated Na and K channel behavior in frog skeletal muscle membrane were studied using a modified double vaseline-gap voltage clamp. The effects of electroconformational damage to ionic channels were separated from damage to lipid bilayer (electroporation). A 4 ms transmembrane potential pulse of -600 mV resulted in a reduction of both Na and K channel conductivities. The supraphysiologic pulses also reduced ionic selectivity of the K channels against Na+ ions, resulting in a depolarization of the membrane resting potential. However, TTX and TEA binding effects were unaltered. The kinetics of spontaneous reversal of the electroconformational damage of channel proteins was found to be dependent on the magnitude of imposed membrane potential pulse. These results suggest that muscle and nerve dysfunction after electrical shock may be in part caused by electroconformational damage to voltage-gated ion channels. PMID:7948676

Calcium-induced calcium release in rod photoreceptor terminals boosts synaptic transmission during maintained depolarization

PubMed Central

Cadetti, Lucia; Bryson, Eric J.; Ciccone, Cory A.; Rabl, Katalin; Thoreson, Wallace B.

2008-01-01

We examined the contribution of calcium-induced calcium release (CICR) to synaptic transmission from rod photoreceptor terminals. Whole-cell recording and confocal calcium imaging experiments were conducted on rods with intact synaptic terminals in a retinal slice preparation from salamander. Low concentrations of ryanodine stimulated calcium increases in rod terminals, consistent with the presence of ryanodine receptors. Application of strong depolarizing steps (−70 to −10 mV) exceeding 200 ms or longer in duration evoked a wave of calcium that spread across the synaptic terminals of voltage-clamped rods. This secondary calcium increase was blocked by high concentrations of ryanodine, indicating it was due to CICR. Ryanodine (50 μM) had no significant effect on rod calcium current (Ica) although it slightly diminished rod light-evoked voltage responses. Bath application of 50 μM ryanodine strongly inhibited light-evoked currents in horizontal cells. Whether applied extracellularly or delivered into the rod cell through the patch pipette, ryanodine (50 μM) also inhibited excitatory post-synaptic currents (EPSCs) evoked in horizontal cells by depolarizing steps applied to rods. Ryanodine caused a preferential reduction in the later portions of EPSCs evoked by depolarizing steps of 200 ms or longer. These results indicate that CICR enhances calcium increases in rod terminals evoked by sustained depolarization, which in turn acts to boost synaptic exocytosis from rods. PMID:16819987

Crayfish neuromuscular facilitation activated by constant presynaptic action potentials and depolarizing pulses.

PubMed

Zucker, R S

1974-08-01

1. Experiments were conducted to test the hypothesis that facilitation of transmitter release in response to repetitive stimulation of the exciter motor axon to the crayfish claw opener muscle is due to an increase in the amplitude or duration of the action potential in presynaptic terminals. No consistent changes were found in the nerve terminal potential (n.t.p.) recorded extracellularly at synaptic sites on the surface of muscle fibres.2. Apparent changes in n.t.p. are attributed to three causes.(i) Some recordings are shown to be contaminated by non-specific muscle responses which grow during facilitation.(ii) Some averaged n.t.p.s exhibit opposite changes in amplitude and duration which suggest a change in the synchrony of presynaptic nerve impulses at different frequencies.(iii) Some changes in n.t.p. are blocked by gamma-methyl glutamate, an antagonist of the post-synaptic receptor, which suggests that these changes are caused by small muscle movements.3. The only change in n.t.p. believed to represent an actual change in the intracellular signal is a reduction in n.t.p. amplitude to the second of two stimuli separated by a brief interval.4. Tetra-ethyl ammonium ions increase synaptic transmission about 20% and prolong the n.t.p. about 15%. This result suggests that an increase in n.t.p. large enough to increase transmission by the several hundred per cent occurring during facilitation would be detected.5. The nerve terminals are electrically excitable, and most synaptic sites have a diphasic or triphasic n.t.p., which suggests that the motor neurone terminals are actively invaded by nerve impulses.6. When nerve impulses are blocked in tetrodotoxin, depolarization of nerve terminals increases the frequency of miniature excitatory junctional potentials (e.j.p.s), and a phasic e.j.p. can be evoked by large, brief depolarizing pulses. Responses to repetitive or paired depolarizations of constant amplitude and duration exhibit a facilitation similar to that of e.j.p.s evoked by nerve impulses.7. It is concluded that facilitation in the crayfish claw opener is not due to a change in the presynaptic action potential, but is due to some change at a later step in the depolarization-secretion process.

Exciting cell membranes with a blustering heat shock.

PubMed

Liu, Qiang; Frerck, Micah J; Holman, Holly A; Jorgensen, Erik M; Rabbitt, Richard D

2014-04-15

Brief heat shocks delivered to cells by pulsed laser light can evoke action potentials in neurons and contraction in cardiomyocytes, but the primary biophysical mechanism has been elusive. In this report we show in the neuromuscular junction of Caenorhabditis elegans that application of a 500°C/s heat shock for 500 μs evoked ~35 pA of excitatory current and injected ~23 fC(femtocoulomb) of charge into the cell while raising the temperature only 0.25°C. The key variable driving the current was the rate of change of temperature (dT/dt heat shock), not temperature itself. The photothermal heat shock current was voltage-dependent and was from thermally driven displacement of ions near the plasma membrane. The charge movement was rapid during the heat shock and slow during thermal relaxation, thus leading to an asymmetrical capacitive current that briefly depolarized the cell. A simple quantitative model is introduced to describe modulation of the membrane potential and facilitate practical application of optical heat shock stimuli. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

The blockade of excitation/contraction coupling by nifedipine in patch-clamped rat skeletal muscle cells in culture.

PubMed

Cognard, C; Rivet, M; Raymond, G

1990-04-01

The effects of the dihydropyridine derivative, nifedipine, well known as a blocker of calcium channels, were tested on cultured rat myoballs. Membrane currents and contractions were simultaneously recorded by means of the patch-clamp technique and a photoelectric transducing method. High concentrations of nifedipine (5 microM) inhibited the contractile responses and inward calcium current (ICa) elicited by long depolarizations. In the absence of ICa (1.5 mM cadmium in the bath), nifedipine inhibited both the ICa-independent contractile component and the outward current, supposed to depend on the intracellular calcium released during contraction. At low concentrations (0.5 microM) the blocking effects of nifedipine could be strongly enhanced by shifting the membrane potential towards less negative values (-60 mV) for 50 s prior to the test pulse. A blocking effect of nifedipine, at a usually ineffective concentration (0.1 microM), could also be observed when long-lasting (3 min) prepulses to 0 mV were applied from a reference membrane potential of -60 mV. This effect could be relieved by long-lasting cell hyperpolarizations (-90 mV). The blocking effects of nifedipine unrelated to ICa could be interpreted as an action on a molecule (voltage sensor) in the T-tubule membrane involved in the excitation/contraction coupling process and as a preferential binding of the dihydropyridine derivative on the inactivated form of this molecule, favored by the weak negative potentials or long-lasting depolarizations. The results provide data in favor of the existence of strong similarities between the calcium channels and voltage sensors since their operation was inhibited in a voltage-dependent manner by nifedipine.

Characterization of two distinct depolarization-activated K+ currents in isolated adult rat ventricular myocytes

PubMed Central

1991-01-01

Depolarization-activated outward K+ currents in isolated adult rat ventricular myocytes were characterized using the whole-cell variation of the patch-clamp recording technique. During brief depolarizations to potentials positive to -40 mV, Ca(2+)-independent outward K+ currents in these cells rise to a transient peak, followed by a slower decay to an apparent plateau. The analyses completed here reveal that the observed outward current waveforms result from the activation of two kinetically distinct voltage-dependent K+ currents: one that activates and inactivates rapidly, and one that activates and inactivates slowly, on membrane depolarization. These currents are referred to here as Ito (transient outward) and IK (delayed rectifier), respectively, because their properties are similar (although not identical) to these K+ current types in other cells. Although the voltage dependences of Ito and IK activation are similar, Ito activates approximately 10-fold and inactivates approximately 30-fold more rapidly than IK at all test potentials. In the composite current waveforms measured during brief depolarizations, therefore, the peak current predominantly reflects Ito, whereas IK is the primary determinant of the plateau. There are also marked differences in the voltage dependences of steady-state inactivation of these two K+ currents: IK undergoes steady-state inactivation at all potentials positive to -120 mV, and is 50% inactivated at -69 mV; Ito, in contrast, is insensitive to steady-state inactivation at membrane potentials negative to -50 mV. In addition, Ito recovers from steady-state inactivation faster than IK: at -90 mV, for example, approximately 70% recovery from the inactivation produced at -20 mV is observed within 20 ms for Ito; IK recovers approximately 25-fold more slowly. The pharmacological properties of Ito and IK are also distinct: 4-aminopyridine preferentially attenuates Ito, and tetraethylammonium suppresses predominantly IK. The voltage- and time- dependent properties of these currents are interpreted here in terms of a model in which Ito underlies the initial, rapid repolarization phase of the action potential (AP), and IK is responsible for the slower phase of AP repolarization back to the resting membrane potential, in adult rat ventricular myocytes. PMID:1865177

Dynamic, nonlinear feedback regulation of slow pacemaking by A-type potassium current in ventral tegmental area neurons.

PubMed

Khaliq, Zayd M; Bean, Bruce P

2008-10-22

We analyzed ionic currents that regulate pacemaking in dopaminergic neurons of the mouse ventral tegmental area by comparing voltage trajectories during spontaneous firing with ramp-evoked currents in voltage clamp. Most recordings were made in brain slice, with key experiments repeated using acutely dissociated neurons, which gave identical results. During spontaneous firing, net ionic current flowing between spikes was calculated from the time derivative of voltage multiplied by cell capacitance, signal-averaged over many firing cycles to enhance resolution. Net inward interspike current had a distinctive nonmonotonic shape, reaching a minimum (generally <1 pA) between -60 and -55 mV. Under voltage clamp, ramps over subthreshold voltages elicited a time- and voltage-dependent outward current that peaked near -55 mV. This current was undetectable with 5 mV/s ramps and increased steeply with depolarization rate over the range (10-50 mV/s) typical of natural pacemaking. Ramp-evoked subthreshold current was resistant to alpha-dendrotoxin, paxilline, apamin, and tetraethylammonium but sensitive to 4-aminopyridine and 0.5 mM Ba2+, consistent with A-type potassium current (I(A)). Same-cell comparison of currents elicited by various ramp speeds with natural spontaneous depolarization showed how the steep dependence of I(A) on depolarization rate results in small net inward currents during pacemaking. These results reveal a mechanism in which subthreshold I(A) is near zero at steady state, but is engaged at depolarization rates >10 mV/s to act as a powerful, supralinear feedback element. This feedback mechanism explains how net ionic current can be constrained to <1-2 pA but reliably inward, thus enabling slow, regular firing.

Completely explosive ultracompact high-voltage nanosecond pulse-generating system

NASA Astrophysics Data System (ADS)

Shkuratov, Sergey I.; Talantsev, Evgueni F.; Baird, Jason; Rose, Millard F.; Shotts, Zachary; Altgilbers, Larry L.; Stults, Allen H.

2006-04-01

A conventional pulsed power technology has been combined with an explosive pulsed power technology to produce an autonomous high-voltage power supply. The power supply contained an explosive-driven high-voltage primary power source and a power-conditioning stage. The ultracompact explosive-driven primary power source was based on the physical effect of shock-wave depolarization of high-energy Pb (Zr52Ti48)O3 ferroelectric material. The volume of the energy-carrying ferroelectric elements in the shock-wave ferroelectric generators (SWFEGs) varied from 1.2 to 2.6cm3. The power-conditioning stage was based on the spiral vector inversion generator (VIG). The SWFEG-VIG system demonstrated successful operation and good performance. The amplitude of the output voltage pulse of the SWFEG-VIG system exceeded 90kV, with a rise time of 5.2ns.

The removal of myoplasmic free calcium following calcium release in frog skeletal muscle.

PubMed Central

Melzer, W; Ríos, E; Schneider, M F

1986-01-01

Transient changes in intracellular free calcium concentration (delta [Ca2+]) in response to pulse depolarizations were monitored in isolated segments of single frog skeletal muscle fibres cut at both ends and voltage clamped at a holding potential of -90 mV in a double-Vaseline-gap chamber. Calcium transients were monitored optically using the metallochromic indicator dye Antipyrylazo III (APIII), which entered the fibre by diffusion from the solution applied to the cut ends. Optical artifacts due to fibre movement were minimized or eliminated by stretching the fibres to sarcomere lengths at which there was little or no overlap of thick and thin contractile filaments. Remaining movement-independent optical changes intrinsic to the fibre and unrelated to the dye were monitored at 850 nm, where free and dye-bound APIII have no absorbance. These 850 nm signals scaled by lambda -1.2 were used to remove intrinsic components from the signals at 700 or 720 nm, wave-lengths at which the APIII absorbance increases when calcium is bound. The corrected 700 or 720 nm signals were used to calculate delta [Ca2+]. The decay of delta [Ca2+] following fibre repolarization at the termination of a depolarizing pulse was well described by a single exponential plus a constant. The exponential rate constant for the decay of delta [Ca2+] decreased and the final 'steady' level that delta [Ca2+] appeared to be approaching increased with increasing amplitude and/or duration of the depolarizing pulse. Both the decreasing decay rate and the build up of the 'steady' level can be accounted for using a two-component model for the removal of free calcium from the myoplasm. One component consists of a set number of a single type of saturable calcium binding site in the myoplasm. The second component is a non-saturable, first-order uptake mechanism operating in parallel with the saturable binding sites. The removal model parameter values were adjusted to fit simultaneously the decay of delta [Ca2+] after pulses of various amplitudes and durations in a given fibre. The basic procedure was to track delta [Ca2+] during each pulse when an undetermined calcium release was occurring, but to calculate the decay of delta [Ca2+] starting 14 ms after repolarization when release was assumed to be negligible. After appropriate selection of parameter values, the model reproduced most aspects of the decay of delta [Ca2+].(ABSTRACT TRUNCATED AT 400 WORDS) PMID:3487641

Modeling-independent elucidation of inactivation pathways in recombinant and native A-type Kv channels

PubMed Central

Fineberg, Jeffrey D.; Ritter, David M.

2012-01-01

A-type voltage-gated K+ (Kv) channels self-regulate their activity by inactivating directly from the open state (open-state inactivation [OSI]) or by inactivating before they open (closed-state inactivation [CSI]). To determine the inactivation pathways, it is often necessary to apply several pulse protocols, pore blockers, single-channel recording, and kinetic modeling. However, intrinsic hurdles may preclude the standardized application of these methods. Here, we implemented a simple method inspired by earlier studies of Na+ channels to analyze macroscopic inactivation and conclusively deduce the pathways of inactivation of recombinant and native A-type Kv channels. We investigated two distinct A-type Kv channels expressed heterologously (Kv3.4 and Kv4.2 with accessory subunits) and their native counterparts in dorsal root ganglion and cerebellar granule neurons. This approach applies two conventional pulse protocols to examine inactivation induced by (a) a simple step (single-pulse inactivation) and (b) a conditioning step (double-pulse inactivation). Consistent with OSI, the rate of Kv3.4 inactivation (i.e., the negative first derivative of double-pulse inactivation) precisely superimposes on the profile of the Kv3.4 current evoked by a single pulse because the channels must open to inactivate. In contrast, the rate of Kv4.2 inactivation is asynchronous, already changing at earlier times relative to the profile of the Kv4.2 current evoked by a single pulse. Thus, Kv4.2 inactivation occurs uncoupled from channel opening, indicating CSI. Furthermore, the inactivation time constant versus voltage relation of Kv3.4 decreases monotonically with depolarization and levels off, whereas that of Kv4.2 exhibits a J-shape profile. We also manipulated the inactivation phenotype by changing the subunit composition and show how CSI and CSI combined with OSI might affect spiking properties in a full computational model of the hippocampal CA1 neuron. This work unambiguously elucidates contrasting inactivation pathways in neuronal A-type Kv channels and demonstrates how distinct pathways might impact neurophysiological activity. PMID:23109714

The negative ultraslow potential, electrophysiological correlate of infarction in the human cortex

PubMed Central

Lückl, Janos; Lemale, Coline L; Kola, Vasilis; Horst, Viktor; Khojasteh, Uldus; Oliveira-Ferreira, Ana I; Major, Sebastian; Winkler, Maren K L; Kang, Eun-Jeung; Schoknecht, Karl; Martus, Peter; Hartings, Jed A; Woitzik, Johannes

2018-01-01

Abstract Spreading depolarizations are characterized by abrupt, near-complete breakdown of the transmembrane ion gradients, neuronal oedema, mitochondrial depolarization, glutamate excitotoxicity and activity loss (depression). Spreading depolarization induces either transient hyperperfusion in normal tissue; or hypoperfusion (inverse coupling = spreading ischaemia) in tissue at risk for progressive injury. The concept of the spreading depolarization continuum is critical since many spreading depolarizations have intermediate characteristics, as opposed to the two extremes of spreading depolarization in either severely ischaemic or normal tissue. In animals, the spreading depolarization extreme in ischaemic tissue is characterized by prolonged depolarization durations, in addition to a slow baseline variation termed the negative ultraslow potential. The negative ultraslow potential is initiated by spreading depolarization and similar to the negative direct current (DC) shift of prolonged spreading depolarization, but specifically refers to a negative potential component during progressive recruitment of neurons into cell death in the wake of spreading depolarization. We here first quantified the spreading depolarization-initiated negative ultraslow potential in the electrocorticographic DC range and the activity depression in the alternate current range after middle cerebral artery occlusion in rats. Relevance of these variables to the injury was supported by significant correlations with the cortical infarct volume and neurological outcome after 72 h of survival. We then identified negative ultraslow potential-containing clusters of spreading depolarizations in 11 patients with aneurysmal subarachnoid haemorrhage. The human platinum/iridium-recorded negative ultraslow potential showed a tent-like shape. Its amplitude of 45.0 (39.0, 69.4) mV [median (first, third quartile)] was 6.6 times larger and its duration of 3.7 (3.3, 5.3) h was 34.9 times longer than the negative DC shift of spreading depolarizations in less compromised tissue. Using Generalized Estimating Equations applied to a logistic regression model, we found that negative ultraslow potential displaying electrodes were significantly more likely to overlie a developing ischaemic lesion (90.0%, 27/30) than those not displaying a negative ultraslow potential (0.0%, 0/20) (P = 0.004). Based on serial neuroimages, the lesions under the electrodes developed within a time window of 72 (56, 134) h. The negative ultraslow potential occurred in this time window in 9/10 patients. It was often preceded by a spreading depolarization cluster with increasingly persistent spreading depressions and progressively prolonged DC shifts and spreading ischaemias. During the negative ultraslow potential, spreading ischaemia lasted for 40.0 (28.0, 76.5) min, cerebral blood flow fell from 57 (53, 65) % to 26 (16, 42) % (n = 4) and tissue partial pressure of oxygen from 12.5 (9.2, 15.2) to 3.3 (2.4, 7.4) mmHg (n = 5). Our data suggest that the negative ultraslow potential is the electrophysiological correlate of infarction in human cerebral cortex and a neuromonitoring-detected medical emergency. PMID:29668855

The negative ultraslow potential, electrophysiological correlate of infarction in the human cortex.

PubMed

Lückl, Janos; Lemale, Coline L; Kola, Vasilis; Horst, Viktor; Khojasteh, Uldus; Oliveira-Ferreira, Ana I; Major, Sebastian; Winkler, Maren K L; Kang, Eun-Jeung; Schoknecht, Karl; Martus, Peter; Hartings, Jed A; Woitzik, Johannes; Dreier, Jens P

2018-06-01

Spreading depolarizations are characterized by abrupt, near-complete breakdown of the transmembrane ion gradients, neuronal oedema, mitochondrial depolarization, glutamate excitotoxicity and activity loss (depression). Spreading depolarization induces either transient hyperperfusion in normal tissue; or hypoperfusion (inverse coupling = spreading ischaemia) in tissue at risk for progressive injury. The concept of the spreading depolarization continuum is critical since many spreading depolarizations have intermediate characteristics, as opposed to the two extremes of spreading depolarization in either severely ischaemic or normal tissue. In animals, the spreading depolarization extreme in ischaemic tissue is characterized by prolonged depolarization durations, in addition to a slow baseline variation termed the negative ultraslow potential. The negative ultraslow potential is initiated by spreading depolarization and similar to the negative direct current (DC) shift of prolonged spreading depolarization, but specifically refers to a negative potential component during progressive recruitment of neurons into cell death in the wake of spreading depolarization. We here first quantified the spreading depolarization-initiated negative ultraslow potential in the electrocorticographic DC range and the activity depression in the alternate current range after middle cerebral artery occlusion in rats. Relevance of these variables to the injury was supported by significant correlations with the cortical infarct volume and neurological outcome after 72 h of survival. We then identified negative ultraslow potential-containing clusters of spreading depolarizations in 11 patients with aneurysmal subarachnoid haemorrhage. The human platinum/iridium-recorded negative ultraslow potential showed a tent-like shape. Its amplitude of 45.0 (39.0, 69.4) mV [median (first, third quartile)] was 6.6 times larger and its duration of 3.7 (3.3, 5.3) h was 34.9 times longer than the negative DC shift of spreading depolarizations in less compromised tissue. Using Generalized Estimating Equations applied to a logistic regression model, we found that negative ultraslow potential displaying electrodes were significantly more likely to overlie a developing ischaemic lesion (90.0%, 27/30) than those not displaying a negative ultraslow potential (0.0%, 0/20) (P = 0.004). Based on serial neuroimages, the lesions under the electrodes developed within a time window of 72 (56, 134) h. The negative ultraslow potential occurred in this time window in 9/10 patients. It was often preceded by a spreading depolarization cluster with increasingly persistent spreading depressions and progressively prolonged DC shifts and spreading ischaemias. During the negative ultraslow potential, spreading ischaemia lasted for 40.0 (28.0, 76.5) min, cerebral blood flow fell from 57 (53, 65) % to 26 (16, 42) % (n = 4) and tissue partial pressure of oxygen from 12.5 (9.2, 15.2) to 3.3 (2.4, 7.4) mmHg (n = 5). Our data suggest that the negative ultraslow potential is the electrophysiological correlate of infarction in human cerebral cortex and a neuromonitoring-detected medical emergency.awy102media15775596049001.

Acute damage threshold for infrared neural stimulation of the cochlea: functional and histological evaluation.

PubMed

Goyal, Vinay; Rajguru, Suhrud; Matic, Agnella I; Stock, Stuart R; Richter, Claus-Peter

2012-11-01

This article provides a mini review of the current state of infrared neural stimulation (INS), and new experimental results concerning INS damage thresholds. INS promises to be an attractive alternative for neural interfaces. With this method, one can attain spatially selective neural stimulation that is not possible with electrical stimulation. INS is based on the delivery of short laser pulses that result in a transient temperature increase in the tissue and depolarize the neurons. At a high stimulation rate and/or high pulse energy, the method bears the risk of thermal damage to the tissue from the instantaneous temperature increase or from potential accumulation of thermal energy. With the present study, we determined the injury thresholds in guinea pig cochleae for acute INS using functional measurements (compound action potentials) and histological evaluation. The selected laser parameters for INS were the wavelength (λ = 1,869 nm), the pulse duration (100 μs), the pulse repetition rate (250 Hz), and the radiant energy (0-127 μJ/pulse). For up to 5 hr of continuous irradiation at 250 Hz and at radiant energies up to 25 μJ/pulse, we did not observe any functional or histological damage in the cochlea. Functional loss was observed for energies above 25 μJ/pulse and the probability of injury to the target tissue resulting in functional loss increased with increasing radiant energy. Corresponding cochlear histology from control animals and animals exposed to 98 or 127 μJ/pulse at 250 Hz pulse repetition rate did not show a loss of spiral ganglion cells, hair cells, or other soft tissue structures of the organ of Corti. Light microscopy did not reveal any structural changes in the soft tissue either. Additionally, microcomputed tomography was used to visualize the placement of the optical fiber within the cochlea. Copyright © 2012 Wiley Periodicals, Inc.

Delayed rectifier K channels contribute to contrast adaptation in mammalian retinal ganglion cells

PubMed Central

Weick, Michael; Demb, Jonathan B.

2011-01-01

SUMMARY Retinal ganglion cells adapt by reducing their sensitivity during periods of high contrast. Contrast adaptation in the firing response depends on both presynaptic and intrinsic mechanisms. Here, we investigated intrinsic mechanisms for contrast adaptation in OFF Alpha ganglion cells in the in vitro guinea pig retina. Using either visual stimulation or current injection, we show that brief depolarization evoked spiking and suppressed firing during subsequent depolarization. The suppression could be explained by Na channel inactivation, as shown in salamander cells. However, brief hyperpolarization in the physiological range (5–10 mV) also suppressed firing during subsequent depolarization. This suppression was sensitive selectively to blockers of delayed-rectifier K channels (KDR). Somatic membrane patches showed TEA-sensitive KDR currents with activation near −25 mV and removal of inactivation at voltages negative to Vrest. Brief periods of hyperpolarization apparently remove KDR inactivation and thereby increase the channel pool available to suppress excitability during subsequent depolarization. PMID:21745646

Delayed-rectifier K channels contribute to contrast adaptation in mammalian retinal ganglion cells.

PubMed

Weick, Michael; Demb, Jonathan B

2011-07-14

Retinal ganglion cells adapt by reducing their sensitivity during periods of high contrast. Contrast adaptation in the firing response depends on both presynaptic and intrinsic mechanisms. Here, we investigated intrinsic mechanisms for contrast adaptation in OFF Alpha ganglion cells in the in vitro guinea pig retina. Using either visual stimulation or current injection, we show that brief depolarization evoked spiking and suppressed firing during subsequent depolarization. The suppression could be explained by Na channel inactivation, as shown in salamander cells. However, brief hyperpolarization in the physiological range (5-10 mV) also suppressed firing during subsequent depolarization. This suppression was selectively sensitive to blockers of delayed-rectifier K channels (K(DR)). In somatic membrane patches, we observed tetraethylammonium-sensitive K(DR) currents that activated near -25 mV. Recovery from inactivation occurred at potentials hyperpolarized to V(rest). Brief periods of hyperpolarization apparently remove K(DR) inactivation and thereby increase the channel pool available to suppress excitability during subsequent depolarization. Copyright © 2011 Elsevier Inc. All rights reserved.

Thermal Stress-Induced Depolarization Loss in Conventional and Panda-Shaped Photonic Crystal Fiber Lasers

NASA Astrophysics Data System (ADS)

Mousavi, Seyedeh Laleh; Sabaeian, Mohammad

2016-10-01

We report on the modeling of the depolarization loss in the conventional and panda-shaped photonic crystal fiber lasers (PCFLs) due to the self-heating of the fiber, which we call it thermal stress-induced depolarization loss (TSIDL). We first calculated the temperature distribution over the fiber cross sections and then calculated the thermal stresses/strains as a function of heat load per meter. Thermal stress-induced birefringence (TSIB), which is defined as | n x - n y |, in the core and cladding regions was calculated. Finally, TSIDL was calculated for the conventional and panda-shaped PCFLs as a function of fiber length and, respectively, saturated values of 22 and 25 % were obtained which were independent of heat load per meter. For panda-shaped PCFLs, prior to being saturated, an oscillating and damping behavior against the fiber length was seen where in some lengths reached 35 %. The results are close to an experimental value of 30 % reported for a pulsed PCFL (Limpert et al., Opt Express 12:1313-1319, 2004) where the authors reported a degree of polarization of 70 % (i.e., a depolarization of 30 %). The most important result of this work is a saturation behavior of TSIDL at long-enough lengths of the fiber laser which is independent of heat load per meter. To our knowledge, this the first report of TSIBL for PCFLs.

Measurement and significance of the reversal potential for the pace-maker current (iK2) in sheep Purkinje fibres.

PubMed

DiFrancesco, D; Ohba, M; Ojeda, C

1979-12-01

1. The apparent reversal potential (Erev) of the pace-maker current (iK2) is found to depend on the experimental protocol used for its measurement. Evidence is presented showing that depolarizing (hyperpolarizing) pulses given before a test hyperpolarization used to determine Erev, shift Erev to more negative (positive) values. These shifts are opposite to those expected if the only effect of pre-pulses were to change the concentration of potassium in extracellular clefts ([K]c) via accumulation and depletion processes. 2. This effect is shown to be due to the fact that Erev is dependent on s0, the degree of activation of iK2 at the start of the test hyperpolarization. 3. When a suitable protocol is used, depletion of cleft K can be demonstrated to take place during a large hyperpolarization. Changes in the level of [K]c induced by pre-pulses must therefore also affect the Erev determination. 4. A simplified three-compartment model has been used to investigate how K accumulation and depletion can affect the time course of iK2, with particular reference to the problem of Erev determination. Computed examples show that the model is able to reproduce the main features of the time course of iK2 recorded near its reversal potential and the changes induced by pre-pulses on Erev measuremnet. By contrast, simulation on a linear cable model rules out the possibility that such results are due to voltage non-uniformity. 5. The three-compartment model predicts that the measured value of Erev differs from EK2 for two reasons: (1) when the recorded current trace is flat iK2 is still outward and decaying, and (2) the K equilibrium potential shifts to more negative values while the test hyperpolarization is applied. 6. The finding that Erev is directly affected by changes in s at the beginning of the test pulse is discussed in relation to the action of agents (such as Ca2+, H+, salicylate, adrenaline and ouabain) which are found to shift both the s00 curve and Erev.

Optical absorption and thermally stimulated depolarization current studies of nickel chloride-doped poly(vinyl alcohol) irradiated with low-level fast neutron doses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abd El-Kader, F.H.; Ibrahim, S.S.; Attia, G.

1993-11-15

The influence of neutron irradiation on ultraviolet/visible absorption and thermally stimulated depolarization current in nickel chloride-poly(vinyl alcohol) (PVA) cast films has been investigated. The spectral measurements indicate the responsibility of the Ni[sup 2][sup +] ion in its octahedral symmetry. Dopant concentrations higher than 10 wt % NiCl[sub 2] are found to make the samples more resistant to a degradation effect caused by neutron irradiation. The thermally stimulated depolarization currents (TSDC) of pure PVA revealed the existence of the glass transition T[sub g] and space charge relaxation peaks, whereas doped-PVA samples show a new sub-T[sub g] relaxation peak. A proposed mechanismmore » is introduced to account for the neutron effects on both glass transition and space charge relaxation peaks. The peak positions, peak currents, and stored charges of the sub-T[sub g] relaxation peak are strongly affected by both the concentration of the dopant and neutron exposure doses.« less

Kinetic and functional analysis of transient, persistent and resurgent sodium currents in rat cerebellar granule cells in situ: an electrophysiological and modelling study

PubMed Central

Magistretti, Jacopo; Castelli, Loretta; Forti, Lia; D'Angelo, Egidio

2006-01-01

Cerebellar neurones show complex and differentiated mechanisms of action potential generation that have been proposed to depend on peculiar properties of their voltage-dependent Na+ currents. In this study we analysed voltage-dependent Na+ currents of rat cerebellar granule cells (GCs) by performing whole-cell, patch-clamp experiments in acute rat cerebellar slices. A transient Na+ current (INaT) was always present and had the properties of a typical fast-activating/inactivating Na+ current. In addition to INaT, robust persistent (INaP) and resurgent (INaR) Na+ currents were observed. INaP peaked at ∼−40 mV, showed half-maximal activation at ∼−55 mV, and its maximal amplitude was about 1.5% of that of INaT. INaR was elicited by repolarizing pulses applied following step depolarizations able to activate/inactivate INaT, and showed voltage- and time-dependent activation and voltage-dependent decay kinetics. The conductance underlying INaR showed a bell-shaped voltage dependence, with peak at −35 mV. A significant correlation was found between GC INaR and INaT peak amplitudes; however, GCs expressing INaT of similar size showed marked variability in terms of INaR amplitude, and in a fraction of cells INaR was undetectable. INaT, INaP and INaR could be accounted for by a 13-state kinetic scheme comprising closed, open, inactivated and blocked states. Current-clamp experiments carried out to identify possible functional correlates of INaP and/or INaR revealed that in GCs single action potentials were followed by depolarizing afterpotentials (DAPs). In a majority of cells, DAPs showed properties consistent with INaR playing a role in their generation. Computer modelling showed that INaR promotes DAP generation and enhances high-frequency firing, whereas INaP boosts near-threshold firing activity. Our findings suggest that special properties of voltage-dependent Na+ currents provides GCs with mechanisms suitable for shaping activity patterns, with potentially important consequences for cerebellar information transfer and computation. PMID:16527854

Sodium efflux from voltage clamped squid giant axons.

PubMed Central

Landowne, D

1977-01-01

1. The efflux of radioactive sodium was measured from squid axons during simultaneous voltage clamp experiments such that it was possible to determine the efflux of sodium associated with a measured voltage clamp current. 2. The extra efflux of sodium associated with voltage clamp pulses increased linearly with the magnitude of the depolarization above 40 mV. A 100 mV pulse of sufficient duration to produce all of the sodium current increased the rate constant of efflux by about 10(-6). 3. Application of 100 nM tetrodotoxin eliminated the sodium current and the extra efflux of radioactive sodium. 4. Cooling the axon increased the extra efflux/voltage clamp pulse slightly with a Q10 of 1/1-1. On the same axons cooling increased the integral of the sodium current with a Q10 of 1/1-4. 5. Replacing external sodium with Tris, dextrose or Mg-mannitol reduced the extra efflux of sodium by about 50%. The inward sodium current was replaced with an outward current as expected. 6. Replacing external sodium with lithium also reduced the extra efflux by about 50% but the currents seen in lithium were slightly larger than those in sodium. 7. The effect of replacing external sodium was not voltage dependent. Cooling reduced the effect so that there was less reduction of efflux on switching to Tris ASW in the cold than in the warm. 8. The extra efflux of sodium into sodium-free ASW is approximately the same as the integral of the sodium current. Adding external sodium produces a deviation from the independence principle such that there is more exchange of sodium than predicted. Such a deviation from prediction was noted by Hodgkin & Huxley (1952c). 9. Using the equations of Hodgkin & Huxley (1952c) modified to include the deviation from independence reported in this paper and its temperature dependence, one can predict the temperature dependence of the sodium efflux associated with action potentials and obtain much better agreement than is possibly without these phenomena. 10. This deviation from independence in the sodium fluxes is the type expected from some kind of mixing and binding of sodium within the membrane phase. PMID:856999

Characteristics of single Ca(2+) channel kinetics in feline hypertrophied ventricular myocytes.

PubMed

Yang, Xiangjun; Hui, Jie; Jiang, Tingbo; Song, Jianping; Liu, Zhihua; Jiang, Wenping

2002-04-01

To explore the mechanism underlying the prolongation of action potential and delayed inactivation of the L-type Ca(2+) (I(Ca, L)) current in a feline model of left ventricular system hypertension and concomitant hypertrophy. Single Ca(2+) channel properties in myocytes isolated from normal and pressure overloaded cat left ventricles were studied, using patch-clamp techniques. Left ventricular pressure overload was induced by partial ligation of the ascending aorta for 4 - 6 weeks. The amplitude of single Ca(2+) channel current evoked by depolarizing pulses from -40 mV to 0 mV was 1.02 +/- 0.03 pA in normal cells and 1.05 +/- 0.03 pA in hypertrophied cells, and there was no difference in single channel current-voltage relationships between the groups since slope conductance was 26.2 +/- 1.0 pS in normal and hypertrophied cells, respectively. Peak amplitudes of the ensemble-averaged single Ca(2+) channel currents were not different between the two groups of cells. However, the amplitude of this averaged current at the end of the clamp pulse was significantly larger in hypertrophied cells than in normal cells. Open-time histograms revealed that open-time distribution was fitted by a single exponential function in channels of normal cells and by a two exponential function in channels of hypertrophied cells. The number of long-lasting openings was increased in channels of hypertrophied cells, and therefore the calculated mean open time of the channel was significantly longer compared to normal controls. Kinetic changes in the Ca(2+) channel may underlie both hypertrophy-associated delayed inactivation of the Ca(2+) current and, in part, the pressure overload-induced action potential lengthening in this cat model of ventricular left systolic hypertension and hypertrophy.

Transcranial Magnetic Stimulation: Basic Principles and Clinical Applications in Migraine.

PubMed

Barker, Anthony T; Shields, Kevin

2017-03-01

Transcranial magnetic stimulation (TMS) is a neurophysiological technique with a long established pedigree of safety, tolerability, and efficacy. Initially TMS was used to study the function of the cerebral cortex, but it has now become a treatment for migraine, one of the most common and debilitating neurological conditions. In this review we discuss the scientific background and development of the technique. We explore its application for the treatment of migraine and ponder the possible mechanisms of action in this most common neurological condition. The generation of brief magnetic pulses by a suitable coil can induce electrical fields in the body. When applied to the cerebral cortex, currents are painlessly induced in cortical neurons. These currents can lead to neuronal depolarization and may influence cortical excitability by means that are as yet not fully understood. This ability to modulate cortical excitability has been exploited as a treatment for migraine with aura. Aura is implicated in the pathophysiology of migraine. Experimental studies have shown that transcranial magnetic pulses can block waves of cortical spreading depression - the experimental equivalent of migrainous aura. Migraine is a debilitating condition characterized by headache, nausea, and sensory hypersensitivity. It may affect up to 15% of the population, yet current drug treatments are often poorly tolerated. Clinical studies have shown that TMS is an effective treatment for migraine. In addition, it has the added advantages of being safe and well tolerated by patients. © 2016 American Headache Society.

Electrophysiology of sodium-coupled transport in proximal renal tubules.

PubMed

Lang, F; Messner, G; Rehwald, W

1986-06-01

Effects of sodium-coupled transport on intracellular electrolytes and electrical properties of proximal renal tubule cells are described in this review. Simultaneous with addition of substrate for sodium-coupled transport to luminal perfusates, both cell membranes depolarize. The luminal cell membrane depolarizes due to opening of sodium-cotransport pathways. The depolarization of the peritubular cell membrane during sodium-coupled transport is primarily due to a circular current reentering the lumen via the paracellular pathway. The depolarization leads to a transient decrease of basolateral potassium conductance that in turn amplifies the depolarization. However, within 5-10 min of continued exposure to substrate, potassium conductance increases again, and peritubular cell membrane repolarizes. During depolarization the driving force of peritubular bicarbonate exit is reduced. As a result net alkalinization of the cell prevails despite an increase of intracellular sodium activity, which reduces the driving force for the sodium-hydrogen ion exchanger and would thus have been expected to acidify the cell. No evidence is obtained for regulatory inhibition of sodium-coupled transport by intracellular sodium or calcium. Rather, luminal cotransport is altered by the change of driving forces.

Computation of interaural time difference in the owl's coincidence detector neurons.

PubMed

Funabiki, Kazuo; Ashida, Go; Konishi, Masakazu

2011-10-26

Both the mammalian and avian auditory systems localize sound sources by computing the interaural time difference (ITD) with submillisecond accuracy. The neural circuits for this computation in birds consist of axonal delay lines and coincidence detector neurons. Here, we report the first in vivo intracellular recordings from coincidence detectors in the nucleus laminaris of barn owls. Binaural tonal stimuli induced sustained depolarizations (DC) and oscillating potentials whose waveforms reflected the stimulus. The amplitude of this sound analog potential (SAP) varied with ITD, whereas DC potentials did not. The amplitude of the SAP was correlated with firing rate in a linear fashion. Spike shape, synaptic noise, the amplitude of SAP, and responsiveness to current pulses differed between cells at different frequencies, suggesting an optimization strategy for sensing sound signals in neurons tuned to different frequencies.

Role of connexin 32 hemichannels in the release of ATP from peripheral nerves.

PubMed

Nualart-Marti, Anna; del Molino, Ezequiel Mas; Grandes, Xènia; Bahima, Laia; Martin-Satué, Mireia; Puchal, Rafel; Fasciani, Ilaria; González-Nieto, Daniel; Ziganshin, Bulat; Llobet, Artur; Barrio, Luis C; Solsona, Carles

2013-12-01

Extracellular purines elicit strong signals in the nervous system. Adenosine-5'-triphosphate (ATP) does not spontaneously cross the plasma membrane, and nervous cells secrete ATP by exocytosis or through plasma membrane proteins such as connexin hemichannels. Using a combination of imaging, luminescence and electrophysiological techniques, we explored the possibility that Connexin 32 (Cx32), expressed in Schwann cells (SCs) myelinating the peripheral nervous system could be an important source of ATP in peripheral nerves. We triggered the release of ATP in vivo from mice sciatic nerves by electrical stimulation and from cultured SCs by high extracellular potassium concentration-evoked depolarization. No ATP was detected in the extracellular media after treatment of the sciatic nerve with Octanol or Carbenoxolone, and ATP release was significantly inhibited after silencing Cx32 from SCs cultures. We investigated the permeability of Cx32 to ATP by expressing Cx32 hemichannels in Xenopus laevis oocytes. We found that ATP release is coupled to the inward tail current generated after the activation of Cx32 hemichannels by depolarization pulses, and it is sensitive to low extracellular calcium concentrations. Moreover, we found altered ATP release in mutated Cx32 hemichannels related to the X-linked form of Charcot-Marie-Tooth disease, suggesting that purinergic-mediated signaling in peripheral nerves could underlie the physiopathology of this neuropathy. Copyright © 2013 Wiley Periodicals, Inc.

Divergent actions of the pyrethroid insecticides S-bioallethrin, tefluthrin, and deltamethrin on rat Na{sub v}1.6 sodium channels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tan Jianguo; Soderlund, David M., E-mail: dms6@cornell.ed

2010-09-15

We expressed rat Na{sub v}1.6 sodium channels in combination with the rat {beta}{sub 1} and {beta}{sub 2} auxiliary subunits in Xenopus laevis oocytes and evaluated the effects of the pyrethroid insecticides S-bioallethrin, deltamethrin, and tefluthrin on expressed sodium currents using the two-electrode voltage clamp technique. S-Bioallethrin, a type I structure, produced transient modification evident in the induction of rapidly decaying sodium tail currents, weak resting modification (5.7% modification at 100 {mu}M), and no further enhancement of modification upon repetitive activation by high-frequency trains of depolarizing pulses. By contrast deltamethrin, a type II structure, produced sodium tail currents that were {approx}more » 9-fold more persistent than those caused by S-bioallethrin, barely detectable resting modification (2.5% modification at 100 {mu}M), and 3.7-fold enhancement of modification upon repetitive activation. Tefluthrin, a type I structure with high mammalian toxicity, exhibited properties intermediate between S-bioallethrin and deltamethrin: intermediate tail current decay kinetics, much greater resting modification (14.1% at 100 {mu}M), and 2.8-fold enhancement of resting modification upon repetitive activation. Comparison of concentration-effect data showed that repetitive depolarization increased the potency of tefluthrin {approx} 15-fold and that tefluthrin was {approx} 10-fold more potent than deltamethrin as a use-dependent modifier of Na{sub v}1.6 sodium channels. Concentration-effect data from parallel experiments with the rat Na{sub v}1.2 sodium channel coexpressed with the rat {beta}{sub 1} and {beta}{sub 2} subunits in oocytes showed that the Na{sub v}1.6 isoform was at least 15-fold more sensitive to tefluthrin and deltamethrin than the Na{sub v}1.2 isoform. These results implicate sodium channels containing the Na{sub v}1.6 isoform as potential targets for the central neurotoxic effects of pyrethroids.« less

Contributions of adaptation currents to dynamic spike threshold on slow timescales: Biophysical insights from conductance-based models

NASA Astrophysics Data System (ADS)

Yi, Guosheng; Wang, Jiang; Wei, Xile; Deng, Bin; Li, Huiyan; Che, Yanqiu

2017-06-01

Spike-frequency adaptation (SFA) mediated by various adaptation currents, such as voltage-gated K+ current (IM), Ca2+-gated K+ current (IAHP), or Na+-activated K+ current (IKNa), exists in many types of neurons, which has been shown to effectively shape their information transmission properties on slow timescales. Here we use conductance-based models to investigate how the activation of three adaptation currents regulates the threshold voltage for action potential (AP) initiation during the course of SFA. It is observed that the spike threshold gets depolarized and the rate of membrane depolarization (dV/dt) preceding AP is reduced as adaptation currents reduce firing rate. It is indicated that the presence of inhibitory adaptation currents enables the neuron to generate a dynamic threshold inversely correlated with preceding dV/dt on slower timescales than fast dynamics of AP generation. By analyzing the interactions of ionic currents at subthreshold potentials, we find that the activation of adaptation currents increase the outward level of net membrane current prior to AP initiation, which antagonizes inward Na+ to result in a depolarized threshold and lower dV/dt from one AP to the next. Our simulations demonstrate that the threshold dynamics on slow timescales is a secondary effect caused by the activation of adaptation currents. These findings have provided a biophysical interpretation of the relationship between adaptation currents and spike threshold.

Depolarization of an Ultrashort Pulse in a Disordered Ensemble of Mie Particles

NASA Astrophysics Data System (ADS)

Gorodnichev, E. E.; Ivliev, S. V.; Kuzovlev, A. I.; Rogozkin, D. B.

2017-12-01

We study propagation of an ultrashort pulse of polarized light through a turbid medium with the Reynolds-McCormick phase function. Within the basic mode approach to the vector radiative transfer equation, the temporal profile of the degree of polarization is calculated analytically with the use of the small-angle approximation. The degree of polarization is shown to be described by the self-similar dependence on some combination of the transport scattering coefficient, the temporal delay and the sample thickness. Our results are in excellent agreement with the data of numerical simulations carried out previously for aqueous suspension of polystyrene microspheres.

Voltage sensitivity of M2 muscarinic receptors underlies the delayed rectifier-like activation of ACh-gated K(+) current by choline in feline atrial myocytes.

PubMed

Navarro-Polanco, Ricardo A; Aréchiga-Figueroa, Iván A; Salazar-Fajardo, Pedro D; Benavides-Haro, Dora E; Rodríguez-Elías, Julio C; Sachse, Frank B; Tristani-Firouzi, Martin; Sánchez-Chapula, José A; Moreno-Galindo, Eloy G

2013-09-01

Choline (Ch) is a precursor and metabolite of the neurotransmitter acetylcholine (ACh). In canine and guinea pig atrial myocytes, Ch was shown to activate an outward K(+) current in a delayed rectifier fashion. This current has been suggested to modulate cardiac electrical activity and to play a role in atrial fibrillation pathophysiology. However, the exact nature and identity of this current has not been convincingly established. We recently described the unique ligand- and voltage-dependent properties of muscarinic activation of ACh-activated K(+) current (IKACh) and showed that, in contrast to ACh, pilocarpine induces a current with delayed rectifier-like properties with membrane depolarization. Here, we tested the hypothesis that Ch activates IKACh in feline atrial myocytes in a voltage-dependent manner similar to pilocarpine. Single-channel recordings, biophysical profiles, specific pharmacological inhibition and computational data indicate that the current activated by Ch is IKACh. Moreover, we show that membrane depolarization increases the potency and efficacy of IKACh activation by Ch and thus gives the appearance of a delayed rectifier activating K(+) current at depolarized potentials. Our findings support the emerging concept that IKACh modulation is both voltage- and ligand-specific and reinforce the importance of these properties in understanding cardiac physiology.

Postsynaptic activity reverses the sign of the acetylcholine-induced long-term plasticity of GABAA inhibition

PubMed Central

Domínguez, Soledad; Fernández de Sevilla, David; Buño, Washington

2014-01-01

Acetylcholine (ACh) regulates forms of plasticity that control cognitive functions but the underlying mechanisms remain largely unknown. ACh controls the intrinsic excitability, as well as the synaptic excitation and inhibition of CA1 hippocampal pyramidal cells (PCs), cells known to participate in circuits involved in cognition and spatial navigation. However, how ACh regulates inhibition in function of postsynaptic activity has not been well studied. Here we show that in rat PCs, a brief pulse of ACh or a brief stimulation of cholinergic septal fibers combined with repeated depolarization induces strong long-term enhancement of GABAA inhibition (GABAA-LTP). Indeed, this enhanced inhibition is due to the increased activation of α5βγ2 subunit-containing GABAA receptors by the GABA released. GABAA-LTP requires the activation of M1-muscarinic receptors and an increase in cytosolic Ca2+. In the absence of PC depolarization ACh triggered a presynaptic depolarization-induced suppression of inhibition (DSI), revealing that postsynaptic activity gates the effects of ACh from presynaptic DSI to postsynaptic LTP. These results provide key insights into mechanisms potentially linked with cognitive functions, spatial navigation, and the homeostatic control of abnormal hyperexcitable states. PMID:24938789

Impossible Dreams, Impossible Choices, and Thoughts about Depolarizing the Debate

ERIC Educational Resources Information Center

Morrow, Susan L.; Beckstead, A. Lee; Hayes, Jeffrey A.; Haldeman, Douglas C.

2004-01-01

The titles of the reactions to this major contribution alone set the stage for further exploration of the issues regarding the hopes and dreams of same-sex attracted (SSA) clients in religious conflict and their therapists, issues of choice, and whether or not it is possible - or even appropriate - to depolarize the current debate (Gonsiorek,…

Input-output relation and energy efficiency in the neuron with different spike threshold dynamics.

PubMed

Yi, Guo-Sheng; Wang, Jiang; Tsang, Kai-Ming; Wei, Xi-Le; Deng, Bin

2015-01-01

Neuron encodes and transmits information through generating sequences of output spikes, which is a high energy-consuming process. The spike is initiated when membrane depolarization reaches a threshold voltage. In many neurons, threshold is dynamic and depends on the rate of membrane depolarization (dV/dt) preceding a spike. Identifying the metabolic energy involved in neural coding and their relationship to threshold dynamic is critical to understanding neuronal function and evolution. Here, we use a modified Morris-Lecar model to investigate neuronal input-output property and energy efficiency associated with different spike threshold dynamics. We find that the neurons with dynamic threshold sensitive to dV/dt generate discontinuous frequency-current curve and type II phase response curve (PRC) through Hopf bifurcation, and weak noise could prohibit spiking when bifurcation just occurs. The threshold that is insensitive to dV/dt, instead, results in a continuous frequency-current curve, a type I PRC and a saddle-node on invariant circle bifurcation, and simultaneously weak noise cannot inhibit spiking. It is also shown that the bifurcation, frequency-current curve and PRC type associated with different threshold dynamics arise from the distinct subthreshold interactions of membrane currents. Further, we observe that the energy consumption of the neuron is related to its firing characteristics. The depolarization of spike threshold improves neuronal energy efficiency by reducing the overlap of Na(+) and K(+) currents during an action potential. The high energy efficiency is achieved at more depolarized spike threshold and high stimulus current. These results provide a fundamental biophysical connection that links spike threshold dynamics, input-output relation, energetics and spike initiation, which could contribute to uncover neural encoding mechanism.

Input-output relation and energy efficiency in the neuron with different spike threshold dynamics

PubMed Central

Yi, Guo-Sheng; Wang, Jiang; Tsang, Kai-Ming; Wei, Xi-Le; Deng, Bin

2015-01-01

Neuron encodes and transmits information through generating sequences of output spikes, which is a high energy-consuming process. The spike is initiated when membrane depolarization reaches a threshold voltage. In many neurons, threshold is dynamic and depends on the rate of membrane depolarization (dV/dt) preceding a spike. Identifying the metabolic energy involved in neural coding and their relationship to threshold dynamic is critical to understanding neuronal function and evolution. Here, we use a modified Morris-Lecar model to investigate neuronal input-output property and energy efficiency associated with different spike threshold dynamics. We find that the neurons with dynamic threshold sensitive to dV/dt generate discontinuous frequency-current curve and type II phase response curve (PRC) through Hopf bifurcation, and weak noise could prohibit spiking when bifurcation just occurs. The threshold that is insensitive to dV/dt, instead, results in a continuous frequency-current curve, a type I PRC and a saddle-node on invariant circle bifurcation, and simultaneously weak noise cannot inhibit spiking. It is also shown that the bifurcation, frequency-current curve and PRC type associated with different threshold dynamics arise from the distinct subthreshold interactions of membrane currents. Further, we observe that the energy consumption of the neuron is related to its firing characteristics. The depolarization of spike threshold improves neuronal energy efficiency by reducing the overlap of Na+ and K+ currents during an action potential. The high energy efficiency is achieved at more depolarized spike threshold and high stimulus current. These results provide a fundamental biophysical connection that links spike threshold dynamics, input-output relation, energetics and spike initiation, which could contribute to uncover neural encoding mechanism. PMID:26074810

Biophysical Insights into How Spike Threshold Depends on the Rate of Membrane Potential Depolarization in Type I and Type II Neurons

PubMed Central

Yi, Guo-Sheng; Wang, Jiang; Tsang, Kai-Ming; Wei, Xi-Le; Deng, Bin

2015-01-01

Dynamic spike threshold plays a critical role in neuronal input-output relations. In many neurons, the threshold potential depends on the rate of membrane potential depolarization (dV/dt) preceding a spike. There are two basic classes of neural excitability, i.e., Type I and Type II, according to input-output properties. Although the dynamical and biophysical basis of their spike initiation has been established, the spike threshold dynamic for each cell type has not been well described. Here, we use a biophysical model to investigate how spike threshold depends on dV/dt in two types of neuron. It is observed that Type II spike threshold is more depolarized and more sensitive to dV/dt than Type I. With phase plane analysis, we show that each threshold dynamic arises from the different separatrix and K+ current kinetics. By analyzing subthreshold properties of membrane currents, we find the activation of hyperpolarizing current prior to spike initiation is a major factor that regulates the threshold dynamics. The outward K+ current in Type I neuron does not activate at the perithresholds, which makes its spike threshold insensitive to dV/dt. The Type II K+ current activates prior to spike initiation and there is a large net hyperpolarizing current at the perithresholds, which results in a depolarized threshold as well as a pronounced threshold dynamic. These predictions are further attested in several other functionally equivalent cases of neural excitability. Our study provides a fundamental description about how intrinsic biophysical properties contribute to the threshold dynamics in Type I and Type II neurons, which could decipher their significant functions in neural coding. PMID:26083350

Light exposure induces short- and long-term changes in the excitability of retinorecipient neurons in suprachiasmatic nucleus

PubMed Central

LeSauter, Joseph; Cloues, Robin; Witkovsky, Paul

2011-01-01

The suprachiasmatic nucleus (SCN) is the locus of a hypothalamic circadian clock that synchronizes physiological and behavioral responses to the daily light-dark cycle. The nucleus is composed of functionally and peptidergically diverse populations of cells for which distinct electrochemical properties are largely unstudied. SCN neurons containing gastrin-releasing peptide (GRP) receive direct retinal input via the retinohypothalamic tract. We targeted GRP neurons with a green fluorescent protein (GFP) marker for whole cell patch-clamping. In these neurons, we studied short (0.5–1.5 h)- and long-term (2–6 h) effects of a 1-h light pulse (LP) given 2 h after lights off [Zeitgeber time (ZT) 14:00–15:00] on membrane potential and spike firing. In brain slices taken from light-exposed animals, cells were depolarized, and spike firing rate increased between ZT 15:30 and 16:30. During a subsequent 4-h period beginning around ZT 17:00, GRP neurons from light-exposed animals were hyperpolarized by ∼15 mV. None of these effects was observed in GRP neurons from animals not exposed to light or in immediately adjacent non-GRP neurons whether or not exposed to light. Depolarization of GRP neurons was associated with a reduction in GABAA-dependent synaptic noise, whereas hyperpolarization was accompanied both by a loss of GABAA drive and suppression of a TTX-resistant leakage current carried primarily by Na. This suggests that, in the SCN, exposure to light may induce a short-term increase in GRP neuron excitability mediated by retinal neurotransmitters and neuropeptides, followed by long-term membrane hyperpolarization resulting from suppression of a leakage current, possibly resulting from genomic signals. PMID:21593396

Contributions of two types of calcium channels to synaptic transmission and plasticity.

PubMed

Edmonds, B; Klein, M; Dale, N; Kandel, E R

1990-11-23

In Aplysia sensory and motor neurons in culture, the contributions of the major classes of calcium current can be selectively examined while transmitter release and its modulation are examined. A slowly inactivating, dihydropyridine-sensitive calcium current does not contribute either to normal synaptic transmission or to any of three different forms of plasticity: presynaptic inhibition, homosynaptic depression, and presynaptic facilitation. This current does contribute, however, to a fourth form of plasticity--modulation of transmitter release by tonic depolarization of the sensory neuron. By contrast, a second calcium current, which is rapidly inactivating and dihydropyridine-insensitive, contributes to release elicited by the transient depolarization of an action potential and to the other three forms of plasticity.

Calcium regulates vesicle replenishment at the cone ribbon synapse

PubMed Central

Babai, Norbert; Bartoletti, Theodore M.; Thoreson, Wallace B.

2010-01-01

Cones release glutamate-filled vesicles continuously in darkness and changing illumination modulates this release. Because sustained release in darkness is governed by vesicle replenishment rates, we analyzed how cone membrane potential regulates replenishment. Synaptic release from cones was measured by recording post-synaptic currents in Ambystoma tigrinum horizontal or OFF bipolar cells evoked by depolarization of simultaneously voltage-clamped cones. We measured replenishment after attaining a steady-state between vesicle release and replenishment using trains of test pulses. Increasing Ca2+ currents (ICa) by changing the test step from −30 to −10 mV increased replenishment. Lengthening −30 mV test pulses to match the Ca2+ influx during 25 ms test pulses to −10 mV produced similar replenishment rates. Reducing Ca2+ driving force by using test steps to +30 mV slowed replenishment. Using UV flashes to reverse inhibition of ICa by nifedipine accelerated replenishment. Increasing [Ca2+]i by flash photolysis of caged Ca2+ also accelerated replenishment. Replenishment, but not the initial burst of release, was enhanced by using an intracellular Ca2+ buffer of 0.5 mM EGTA rather than 5 mM EGTA, and diminished by 1 mM BAPTA. This suggests that although release and replenishment and release exhibited similar Ca2+-dependencies, release sites are <200 nm from Ca2+ channels but replenishment sites are >200 nm away. Membrane potential thus regulates replenishment by controlling Ca2+ influx, principally by effects on replenishment mechanisms but also by altering releasable pool size. This in turn provides a mechanism for converting changes in light intensity into changes in sustained release at the cone ribbon synapse. PMID:21106825

Endogenous cannabinoids mediate retrograde signals from depolarized postsynaptic neurons to presynaptic terminals.

PubMed

Ohno-Shosaku, T; Maejima, T; Kano, M

2001-03-01

Endogenous cannabinoids are considered to function as diffusible and short-lived modulators that may transmit signals retrogradely from postsynaptic to presynaptic neurons. To evaluate this possibility, we have made a paired whole-cell recording from cultured hippocampal neurons with inhibitory synaptic connections. In about 60% of pairs, a cannabinoid agonist greatly reduced the release of the inhibitory neurotransmitter GABA from presynaptic terminals. In most of such pairs but not in those insensitive to the agonist, depolarization of postsynaptic neurons and the resultant elevation of intracellular Ca2+ concentration caused transient suppression of inhibitory synaptic currents, which is mainly due to reduction of GABA release. This depolarization-induced suppression was completely blocked by selective cannabinoid antagonists. Our results reveal that endogenous cannabinoids mediate retrograde signals from depolarized postsynaptic neurons to presynaptic terminals to cause the reduction of transmitter release.

Electrophysiology of the mammillary complex in vitro. I. Tuberomammillary and lateral mammillary neurons

NASA Technical Reports Server (NTRS)

Llinas, R. R.; Alonso, A.

1992-01-01

1. The electrophysiological properties of the tuberomammillary and lateral mammillary neurons in the guinea pig mammillary body were studied using an in vitro brain slice preparation. 2. Tuberomammillary (n = 79) neurons were recorded mainly ventral to the lateral mammillary body as well as ventromedially to the fornix within the rostral part of the medial mammillary nucleus. Intracellular staining with horseradish peroxidase (n = 9) and Lucifer yellow (n = 3) revealed that these cells have several thick, long, spiny dendrites emerging from large (20-35 microns) fusiform somata. 3. Most tuberomammillary neurons (66%) fired spontaneously at a relatively low frequency (0.5-10 Hz) at the resting membrane potential. The action potentials were broad (2.3 ms) with a prominent Ca(2+)-dependent shoulder on the falling phase. Deep (17.8 mV), long-lasting spike afterhyperpolarizations were largely Ca(2+)-independent. 4. All tuberomammillary neurons recorded displayed pronounced delayed firing when the cells were activated from a potential negative to the resting level. The cells also displayed a delayed return to the baseline at the break of hyperpolarizing pulses applied from a membrane potential level close to firing threshold. Analysis of the voltage- and time dependence of this delayed rectification suggested the presence of a transient outward current similar to the A current (IA). These were not completely blocked by high concentrations of 4-aminopyridine, whereas the delayed onset of firing was always abolished when voltage-dependent Ca2+ conductances were blocked by superfusion with Cd2+. 5. Tuberomammillary neurons also displayed inward rectification in the hyperpolarizing and, primarily, depolarizing range. Block of voltage-gated Na(+)-dependent conductances with tetrodotoxin (TTX) selectively abolished inward rectification in the depolarizing range, indicating the presence of a persistent low-threshold sodium-dependent conductance (gNap). In fact, persistent TTX-sensitive, plateau potentials were always elicited following Ca2+ block with Cd2+ when K+ currents were reduced by superfusion with tetraethylammonium. 6. The gNap in tuberomammillary neurons may subserve the pacemaker current underlying the spontaneous firing of these cells. The large-amplitude spike afterhyperpolarization of these neurons sets the availability of the transient outward rectifier, which, in conjunction with the pacemaker current, establishes the rate at which membrane potential approaches spike threshold. 7. Repetitive firing elicited by direct depolarization enhanced the spike shoulder of tuberomammillary neurons. Spike trains were followed by a Ca(2+)-dependent, apamine-sensitive, slow afterhyperpolarization. 8. Lateral mammillary neurons were morphologically and electrophysiologically different from tuberomammillary neurons. All lateral mammillary neurons neurons recorded (n = 44) were silent at rest (-60 mV).(ABSTRACT TRUNCATED AT 400 WORDS).

Physiological Characterization of Vestibular Efferent Brainstem Neurons Using a Transgenic Mouse Model

PubMed Central

Leijon, Sara; Magnusson, Anna K.

2014-01-01

The functional role of efferent innervation of the vestibular end-organs in the inner ear remains elusive. This study provides the first physiological characterization of the cholinergic vestibular efferent (VE) neurons in the brainstem by utilizing a transgenic mouse model, expressing eGFP under a choline-acetyltransferase (ChAT)-locus spanning promoter in combination with targeted patch clamp recordings. The intrinsic electrical properties of the eGFP-positive VE neurons were compared to the properties of the lateral olivocochlear (LOC) brainstem neurons, which gives rise to efferent innervation of the cochlea. Both VE and the LOC neurons were marked by their negative resting membrane potential <−75 mV and their passive responses in the hyperpolarizing range. In contrast, the response properties of VE and LOC neurons differed significantly in the depolarizing range. When injected with positive currents, VE neurons fired action potentials faithfully to the onset of depolarization followed by sparse firing with long inter-spike intervals. This response gave rise to a low response gain. The LOC neurons, conversely, responded with a characteristic delayed tonic firing upon depolarizing stimuli, giving rise to higher response gain than the VE neurons. Depolarization triggered large TEA insensitive outward currents with fast inactivation kinetics, indicating A-type potassium currents, in both the inner ear-projecting neuronal types. Immunohistochemistry confirmed expression of Kv4.3 and 4.2 ion channel subunits in both the VE and LOC neurons. The difference in spiking responses to depolarization is related to a two-fold impact of these transient outward currents on somatic integration in the LOC neurons compared to in VE neurons. It is speculated that the physiological properties of the VE neurons might be compatible with a wide-spread control over motion and gravity sensation in the inner ear, providing likewise feed-back amplification of abrupt and strong phasic signals from the semi-circular canals and of tonic signals from the gravito-sensitive macular organs. PMID:24867596

Recent Advances in the Pathogenesis and Drug Action in Periodic Paralyses and Related Channelopathies

PubMed Central

Tricarico, Domenico; Camerino, Diana Conte

2011-01-01

The periodic paralysis (PP) are rare autosomal-dominant disorders associated to mutations in the skeletal muscle sodium, calcium, and potassium channel genes characterized by muscle fiber depolarization with un-excitability, episodes of weakness with variations in serum potassium concentrations. Recent advances in thyrotoxic PP and hypokalemic PP (hypoPP) confirm the involvement of the muscle potassium channels in the pathogenesis of the diseases and their role as target of action for drugs of therapeutic interest. The novelty in the gating pore currents theory help to explain the disease symptoms, and open the possibility to more specifically target the disease. It is now known that the fiber depolarization in the hypoPP is due to an unbalance between the novel identified depolarizing gating pore currents (Igp) carried by protons or Na+ ions flowing through aberrant alternative pathways of the mutant subunits and repolarizing inwardly rectifying potassium channel (Kir) currents which also includes the ATP-sensitive subtype. Abnormal activation of the Igp or deficiency in the Kir channels predispose to fiber depolarization. One pharmacological strategy is based on blocking the Igp without affecting normal channel gating. It remains safe and effective the proposal of targeting the KATP, Kir channels, or BK channels by drugs capable to specifically open at nanomolar concentrations the skeletal muscle subtypes with less side effects. PMID:21687503

Asymmetrical electrically induced injury of rabbit ventricular myocytes.

PubMed

Knisley, S B; Grant, A O

1995-05-01

Strong defibrillation-type electric field stimulation may injure myocytes when transmembrane potentials during the pulse exceed the threshold for membrane permeabilization. The location of injury may depend on intrinsic transmembrane potential or influx of calcium by "electro-osmosis" during the stimulation pulse in addition to the transmembrane potential changes induced by the pulse. We have studied injury by examining contracture and changes in transmembrane potential-sensitive dye fluorescence induced by electric field stimulation (St) with a duration of 20 ms and strength of 16-400 V/cm in isolated rabbit ventricular myocytes. St of 100-150 V/cm produced injury in myocytes oriented parallel to the St field frequently without injuring myocytes oriented perpendicular to the field. Injury required calcium in the solution and was asymmetric, occurring first at the myocyte and facing the St anode in 100% of injured myocytes in normal Tyrode's solution. Injury depended significantly on whether the product of the electric field strength and myocyte length exceeded a threshold of 1.1 V (P < 0.05). Asymmetric injury at the end facing the anode was still present in 96% of injured myocytes for stimulation after depolarization by an action potential or 20 mM or 125 mM potassium, suggesting that intrinsic transmembrane potential is not responsible for asymmetry. In 125 mM potassium, eliminating calcium from the bathing solution during the St pulse and introducing calcium after the pulse decreased the fraction of injured myocytes in which injury occurred at the end facing the anode to 62%, suggesting that calcium influx by "electro-osmosis" at the myocyte end facing the anode contributes to asymmetry. Asymmetric injury at the end facing the anode was still present in 100% of injured myocytes after adding 1 mM tetraethylammonium chloride, indicating that asymmetry is not sensitive to the potassium channel blockade. For stimulation pulses stronger than 50 V/cm given after depolarization by an action potential, transmembrane potentials at both myocyte ends decayed after the initial deflection indicating that permeabilization occurred at both ends. In conclusion, injury depends on myocyte orientation and is asymmetric occurring first at the myocyte end facing the anode. Asymmetric injury is not explained by asymmetric permeabilization, is independent of the intrinsic transmembrane potential and may result from "electro-osmosis" during the stimulation pulse.

Proton transport polarization and depolarization of hydroxyapatite ceramics

NASA Astrophysics Data System (ADS)

Nakamura, Satoshi; Takeda, Hiroaki; Yamashita, Kimihiro

2001-05-01

Polarization of sintered hydroxyapatite (HAp) ceramics by application of an external dc field at higher temperature was analyzed by thermally stimulated depolarization current (TSDC) measurements. The mechanisms for the polarization and depolarization of HAp were discussed in relation to the instability of the protons in the hydroxide groups. The TSDC spectra consisted of broad peaks, while the ferroelectric substances such as the BaTiO3 ceramics exhibited a sharp peak. Although the maximum current density of 7.87 nA cm-2 for the HAp polarized at 400 °C under 1.0 kV cm-1 was approximately 1/12 lower than that of BaTiO3, the polarization charge of 14.9 μC cm-2 was almost twice as large as that of BaTiO3. Considering the activation energy of 0.72-0.89 eV for the depolarization, it was revealed that the polarization of HAp was ascribed to the migration of protons in the columnar OH- channels with a micrometer-order distance. It was also found that the polarization charge was large and long enough to enhance the biological reactivity of HAp ceramics for biomedical implants.

Bi-stable dendrite in constant electric field: a model analysis.

PubMed

Baginskas, A; Gutman, A; Svirskis, G

1993-03-01

Some neurons possess dendritic persistent inward current, which is activated during depolarization. Dendrites can be stably depolarized, i.e. they are bi-stable if the net current is inward. A proper method to show the existence of dendritic bi-stability is putting the neuron into the electric field to induce transmembrane potential changes along the dendrites. Here we present analytical and computer simulation of the bi-stable dendrite in the d.c. field. A prominent jump to a depolarization plateau can be seen in the soma upon initial hyperpolarization of its membrane. If a considerable portion of dendrites are parallel to the field it is impossible to switch off the depolarization plateau by changing the direction and the strength of the electric field. There is nothing similar in neurons with ohmic dendrites. The results of the simulation conform to the experimental observations in turtle motoneurons [Hounsgaard J. and Kiehn O. (1993) J. Physiol., Lond. (in press)]; comparison of the theoretical and the experimental results makes semi-quantitative estimation of some electrical parameters of dendrites possible. We propose modifications of the experiment which enable one to measure dendritic length constants and other parameters of stained neurons.

Transient sodium current at subthreshold voltages: activation by EPSP waveforms

PubMed Central

Carter, Brett C.; Giessel, Andrew J.; Sabatini, Bernardo L.; Bean, Bruce P.

2012-01-01

Summary Tetrodotoxin (TTX)-sensitive sodium channels carry large transient currents during action potentials and also “persistent” sodium current, a non-inactivating TTX-sensitive current present at subthreshold voltages. We examined gating of subthreshold sodium current in dissociated cerebellar Purkinje neurons and hippocampal CA1 neurons, studied at 37 °C with near-physiological ionic conditions. Unexpectedly, in both cell types small voltage steps at subthreshold voltages activated a substantial component of transient sodium current as well as persistent current. Subthreshold EPSP-like waveforms also activated a large component of transient sodium current, but IPSP-like waveforms engaged primarily persistent sodium current with only a small additional transient component. Activation of transient as well as persistent sodium current at subthreshold voltages produces amplification of EPSPs that is sensitive to the rate of depolarization and can help account for the dependence of spike threshold on depolarization rate, as previously observed in vivo. PMID:22998875

Near-surface and columnar measurements with a micro pulse lidar of atmospheric pollen in Barcelona, Spain

NASA Astrophysics Data System (ADS)

Sicard, Michaël; Izquierdo, Rebeca; Alarcón, Marta; Belmonte, Jordina; Comerón, Adolfo; Baldasano, José Maria

2016-06-01

We present for the first time continuous hourly measurements of pollen near-surface concentration and lidar-derived profiles of particle backscatter coefficients and of volume and particle depolarization ratios during a 5-day pollination event observed in Barcelona, Spain, between 27 and 31 March 2015. Daily average concentrations ranged from 1082 to 2830 pollen m-3. Platanus and Pinus pollen types represented together more than 80 % of the total pollen. Maximum hourly pollen concentrations of 4700 and 1200 m-3 were found for Platanus and Pinus, respectively. Every day a clear diurnal cycle caused by the vertical transport of the airborne pollen was visible on the lidar-derived profiles with maxima usually reached between 12:00 and 15:00 UT. A method based on the lidar polarization capabilities was used to retrieve the contribution of the pollen to the total aerosol optical depth (AOD). On average the diurnal (09:00-17:00 UT) pollen AOD was 0.05, which represented 29 % of the total AOD. Maximum values of the pollen AOD and its contribution to the total AOD reached 0.12 and 78 %, respectively. The diurnal means of the volume and particle depolarization ratios in the pollen plume were 0.08 and 0.14, with hourly maxima of 0.18 and 0.33, respectively. The diurnal mean of the height of the pollen plume was found at 1.24 km with maxima varying in the range of 1.47-1.78 km. A correlation study is performed (1) between the depolarization ratios and the pollen near-surface concentration to evaluate the ability of the former parameter to monitor pollen release and (2) between the depolarization ratios as well as pollen AOD and surface downward solar fluxes, which cause the atmospheric turbulences responsible for the particle vertical motion, to examine the dependency of the depolarization ratios and the pollen AOD upon solar fluxes. For the volume depolarization ratio the first correlation study yields to correlation coefficients ranging 0.00-0.81 and the second to correlation coefficients ranging 0.49-0.86.

Proton-Mediated Block of Ca2+ Channels during Multivesicular Release Regulates Short-Term Plasticity at an Auditory Hair Cell Synapse

PubMed Central

Cho, Soyoun

2014-01-01

Synaptic vesicles release both neurotransmitter and protons during exocytosis, which may result in a transient acidification of the synaptic cleft that can block Ca2+ channels located close to the sites of exocytosis. Evidence for this effect has been reported for retinal ribbon-type synapses, but not for hair cell ribbon synapses. Here, we report evidence for proton release from bullfrog auditory hair cells when they are held at more physiological, in vivo–like holding potentials (Vh = −60 mV) that facilitate multivesicular release. During paired recordings of hair cells and afferent fibers, L-type voltage-gated Ca2+ currents showed a transient block, which was highly correlated with the EPSC amplitude (or the amount of glutamate release). This effect was masked at Vh = −90 mV due to the presence of a T-type Ca2+ current and blocked by strong pH buffering with HEPES or TABS. Increasing vesicular pH with internal methylamine in hair cells also abolished the transient block. High concentrations of intracellular Ca2+ buffer (10 mm BAPTA) greatly reduced exocytosis and abolished the transient block of the Ca2+ current. We estimate that this transient block is due to the rapid multivesicular release of ∼600–1300 H+ ions per synaptic ribbon. Finally, during a train of depolarizing pulses, paired pulse plasticity was significantly changed by using 40 mm HEPES in addition to bicarbonate buffer. We propose that this transient block of Ca2+ current leads to more efficient exocytosis per Ca2+ ion influx and it may contribute to spike adaptation at the auditory nerve. PMID:25429130

Modulation of Pacemaker Potentials in Murine Small Intestinal Interstitial Cells of Cajal by Gamisoyo-San, a Traditional Chinese Herbal Medicine.

PubMed

Kim, Doeun; Kim, Jung Nam; Nam, Joo Hyun; Lee, Jong Rok; Kim, Sang Chan; Kim, Byung Joo

2018-04-19

The Gamisoyo-san (GSS) has been used for -improving the gastrointestinal (GI) symptoms. The purpose of this study was to investigate the effects of GSS, a traditional Chinese herbal medicine, on the pacemaker potentials of mouse small intestinal interstitial cells of Cajal (ICCs). ICCs from the small intestines were dissociated and cultured. Whole-cell patch-clamp configuration was used to record pacemaker potentials and membrane currents. GSS depolarized ICC pacemaker potentials in a dose-dependent manner. Pretreatment with 4-diphenylacetoxypiperidinium iodide completely inhibited GSS-induced pacemaker potential depolarizations. Intracellular GDP-β-S inhibited GSS-induced effects, and in the presence of U-73122, GSS-induced effects were inhibited. Also, GSS in the presence of a Ca2+-free solution or thapsigargin did not depolarize pacemaker potentials. However, in the presence of calphostin C, GSS slightly depolarized pacemaker potentials. Furthermore, GSS inhibited both transient receptor potential melastatin7 and Ca2+-activated Cl- channel (anoctamin1) currents. GSS depolarized pacemaker potentials of ICCs via G protein and muscarinic M3 receptor signaling pathways and through internal or external Ca2+-, phospholipase C-, and protein kinase C-dependent and transient receptor potential melastatin 7-, and anoctamin 1-independent pathways. The study shows that GSS may regulate GI tract motility, suggesting that GSS could be a basis for developing novel prokinetic agents for treating GI motility dysfunctions. © 2018 S. Karger AG, Basel.

A New Pulse Shape to Obtain Selective Small Fiber Activation by Anodal Blocking

DTIC Science & Technology

2001-10-25

anodal blocking a tripolar cuff electrode is most commonly used. When external stimulation is applied, the fiber membrane is depolarized close to...would be safer if somehow the charge per phase could be reduced. Charge reduction might be possible with the following idea: In a tripolar cuff...inhomogeneous and anisotropic volume conductor model [3]. A symmetrical tripolar cuff electrode with an inner diameter of 2 mm was placed around a

Piezoelectric Polymer Films for Application in Monitoring Devices

DTIC Science & Technology

1977-02-01

pulse is also evident, as is the decay rate of the pressure, and what appears to be a pronounced " dicrotic notch ," which is asso- ciated with heart valve...investigation of factors responsible for this remark- able behavior of an organic polymer. Commercial PVF 2 homopolymer and copolymer films were oriented by... factors such as changes in elastic modulus of the film with temperature, depolarization processes at the higher temperature, and pyroelectric effects

Properties of an intermediate-duration inactivation process of the voltage-gated sodium conductance in rat hippocampal CA1 neurons.

PubMed

French, Christopher R; Zeng, Zhen; Williams, David A; Hill-Yardin, Elisa L; O'Brien, Terence J

2016-02-01

Rapid transmembrane flow of sodium ions produces the depolarizing phase of action potentials (APs) in most excitable tissue through voltage-gated sodium channels (NaV). Macroscopic currents display rapid activation followed by fast inactivation (IF) within milliseconds. Slow inactivation (IS) has been subsequently observed in several preparations including neuronal tissues. IS serves important physiological functions, but the kinetic properties are incompletely characterized, especially the operative timescales. Here we present evidence for an "intermediate inactivation" (II) process in rat hippocampal CA1 neurons with time constants of the order of 100 ms. The half-inactivation potentials (V0.5) of steady-state inactivation curves were hyperpolarized by increasing conditioning pulse duration from 50 to 500 ms and could be described by a sum of Boltzmann relations. II state transitions were observed after opening as well as subthreshold potentials. Entry into II after opening was relatively insensitive to membrane potential, and recovery of II became more rapid at hyperpolarized potentials. Removal of fast inactivation with cytoplasmic papaine revealed time constants of INa decay corresponding to II and IS with long depolarizations. Dynamic clamp revealed attenuation of trains of APs over the 10(2)-ms timescale, suggesting a functional role of II in repetitive firing accommodation. These experimental findings could be reproduced with a five-state Markov model. It is likely that II affects important aspects of hippocampal neuron response and may provide a drug target for sodium channel modulation. Copyright © 2016 the American Physiological Society.

Bone mineral as an electrical energy reservoir.

PubMed

Nakamura, Miho; Hiratai, Rumi; Yamashita, Kimihiro

2012-05-01

Mechanical stress in bone induces an electrical potential generated by piezoelectricity arising from displacement of collagen fibrils. Where and for how long the potential is stored in bone; however, are still poorly understood. We investigated the electrical properties of collagen fibrils and apatite minerals and found that bone, when polarized electrically by applying an external voltage, depolarizes by two mechanisms. Plots of thermally stimulated depolarization current show two significant peaks: one at 100°C, attributed to collagen fibrils because decalcified bone exhibits depolarization peak at 100°C, and the other at 500°C, attributed to apatite minerals because calcined bone exhibits depolarization peak at 500°C and has activation energy similar to that for synthesized apatite. The crystallographic c-axis orientation of calcined bone depends on the direction in which the bone is cut, either transverse or longitudinal, and strongly affects the polarization efficacy. Copyright © 2012 Wiley Periodicals, Inc.

Crayfish neuromuscular facilitation activated by constant presynaptic action potentials and depolarizing pulses

PubMed Central

Zucker, Robert S.

1974-01-01

1. Experiments were conducted to test the hypothesis that facilitation of transmitter release in response to repetitive stimulation of the exciter motor axon to the crayfish claw opener muscle is due to an increase in the amplitude or duration of the action potential in presynaptic terminals. No consistent changes were found in the nerve terminal potential (n.t.p.) recorded extracellularly at synaptic sites on the surface of muscle fibres. 2. Apparent changes in n.t.p. are attributed to three causes. (i) Some recordings are shown to be contaminated by non-specific muscle responses which grow during facilitation. (ii) Some averaged n.t.p.s exhibit opposite changes in amplitude and duration which suggest a change in the synchrony of presynaptic nerve impulses at different frequencies. (iii) Some changes in n.t.p. are blocked by γ-methyl glutamate, an antagonist of the post-synaptic receptor, which suggests that these changes are caused by small muscle movements. 3. The only change in n.t.p. believed to represent an actual change in the intracellular signal is a reduction in n.t.p. amplitude to the second of two stimuli separated by a brief interval. 4. Tetra-ethyl ammonium ions increase synaptic transmission about 20% and prolong the n.t.p. about 15%. This result suggests that an increase in n.t.p. large enough to increase transmission by the several hundred per cent occurring during facilitation would be detected. 5. The nerve terminals are electrically excitable, and most synaptic sites have a diphasic or triphasic n.t.p., which suggests that the motor neurone terminals are actively invaded by nerve impulses. 6. When nerve impulses are blocked in tetrodotoxin, depolarization of nerve terminals increases the frequency of miniature excitatory junctional potentials (e.j.p.s), and a phasic e.j.p. can be evoked by large, brief depolarizing pulses. Responses to repetitive or paired depolarizations of constant amplitude and duration exhibit a facilitation similar to that of e.j.p.s evoked by nerve impulses. 7. It is concluded that facilitation in the crayfish claw opener is not due to a change in the presynaptic action potential, but is due to some change at a later step in the depolarization—secretion process. PMID:4153766

Inhibitory control of plateau properties in dorsal horn neurones in the turtle spinal cord in vitro

PubMed Central

Russo, Raúl E; Nagy, Frédéric; Hounsgaard, Jørn

1998-01-01

The role of inhibition in control of plateau-generating neurones in the dorsal horn was studied in an in vitro preparation of the spinal cord of the turtle. Ionotropic and metabotropic inhibition was found to condition the expression of plateau potentials. Blockade of γ-aminobutyric acid (GABAA) and glycine receptors by their selective antagonists bicuculline (10-50 μM) and strychnine (5-20 μM) enhanced the excitatory response to stimulation of the dorsal root and facilitated the expression of plateau potentials. Bicuculline and strychnine also facilitated the generation of plateau potentials in response to depolarizing current pulses, suggesting the presence of tonic ionotropic inhibitory mechanisms in turtle spinal cord slices. Activation of GABAB receptors also inhibited plateau-generating neurones. The selective agonist baclofen (5-50 μM) inhibited wind-up of the response to repeated depolarizations induced synaptically or by intracellular current pulses. Baclofen reduced afferent synaptic input. This effect was not affected by bicuculline or strychnine and was blocked by the selective GABAB receptor antagonist 2-hydroxysaclofen (2-OH-saclofen, 100-400 μM). Postsynaptically, baclofen inhibited plateau properties. Activation of GABAB receptors produced a hyperpolarization (7.0 ± 0.5 mV, mean ± s.e.m., n= 29) with an associated decrease in input resistance (22.7 ± 3.1 %, n= 24). These effects were blocked by extracellular Ba2+ (1-2 mM). When the baclofen-induced hyperpolarization and shunt were compensated for by adjusting the bias current and the strength of the stimulus, baclofen still inhibited generation of plateau potentials. Wind-up and after-discharges were also inhibited by baclofen. These effects remained in the presence of tetrodotoxin (1 μM) and were antagonized by 2-OH-saclofen. The inhibition of plateau properties was observed even when the baclofen-induced hyperpolarization and shunt were blocked by Ba2+ and when potassium channels were blocked by Ba2+ (3 mM), tetraethylammonium (TEA, 15 mM) and apamin (0.25-0.5 μM). The baclofen-sensitive component of the plateau potential was reduced by nifedipine (10 μM), suggesting a modulation of postsynaptic L-type Ca2+ channels. We suggest that inhibitory regulation of plateau properties plays a role in somatosensory processing in the dorsal horn. The inhibitory control of wind-up and after-discharges may be particularly significant in physiological and therapeutic control of central sensitization to pain. PMID:9503338

Tetrodotoxin-sensitive, voltage-dependent sodium currents in hair cells from the alligator cochlea.

PubMed

Evans, M G; Fuchs, P A

1987-10-01

We have used whole-cell patch clamp techniques to record from tall hair cells isolated from the apical half of the alligator cochlea. Some of these cells gave action potentials in response to depolarizing current injections. When the same cells were voltage clamped, large transient inward currents followed by smaller outward currents were seen in response to depolarizing steps. We studied the transient inward current after the outward current had been blocked by external tetraethylammonium (20 mM) or by replacing internal potassium with cesium. It was found to be a sodium current because it was abolished by either replacing external sodium with choline or by external application of tetrodotoxin (100 nM). The sodium current showed voltage-dependent activation and inactivation. Most of the spiking hair cells came from the apex of the cochlea, where they would be subject to low-frequency mechanical stimulation in vivo.

Characteristics of 5-HT-containing chemoreceptor cells of the chicken aortic body

PubMed Central

Ito, Shigeo; Ohta, Toshio; Nakazato, Yoshikazu

1999-01-01

Voltage-dependent and oxygen-sensitive currents in 5-HT-containing epithelioid cells isolated from chicken thoracic aorta were examined using the whole-cell patch clamp technique. 5-HT immunoreactive cells were identified with Neutral Red. The release of 5-HT from chicken thoracic aorta in the presence of excess KCl and veratridine was also examined using HPLC. At a holding potential of −70 mV with CsCl pipette solution, depolarizing steps between −30 and +60 mV produced inward currents that were blocked by tetrodotoxin (0.2 μm). In the presence of tetrodotoxin and BaCl2 (5 mm), depolarizing steps evoked slow inward currents that were sensitive to CoCl2 (2 mm). Nifedipine (1 μm) decreased the currents to 79.4 ± 1.7%, and ω-conotoxin GVIA (1 μm) to 20.2 ± 3.8%. When KCl pipette solution was used, depolarizing potentials positive to −40 mV caused outward currents that were inhibited by tetraethylammonium chloride. The K+ currents evoked by depolarizing steps to +20 mV were reduced to 90.3 ± 0.8% by hypoxia in five out of seven cells. Two cells failed to respond to hypoxia. The K+ current response was partly decreased by Neutral Red (20 μm). Excess KCl (60 mm) and veratridine (30 μm) both caused the release of 5-HT from aortic strips. 5-HT outputs induced by both stimuli were partly inhibited by nifedipine (1 μm) and by ω-conotoxin GVIA (1 μm), and were abolished by these drugs in combination and by extracellular Ca2+ removal. These results suggest that epithelioid cells containing 5-HT act as chemoreceptor cells in the chicken aortic body, having voltage-dependent Na+, K+, and L- and N-type Ca2+ channels, and oxygen-sensitive K+ channels. PMID:9925877

NADH fluorescence imaging and the histological impact of cortical spreading depolarization during the acute phase of subarachnoid hemorrhage in rats.

PubMed

Shimizu, Tomohisa; Hishikawa, Tomohito; Nishihiro, Shingo; Shinji, Yukei; Takasugi, Yuji; Haruma, Jun; Hiramatsu, Masafumi; Kawase, Hirokazu; Sato, Sachiko; Mizoue, Ryoichi; Takeda, Yoshimasa; Sugiu, Kenji; Morimatsu, Hiroshi; Date, Isao

2018-01-01

OBJECTIVE Although cortical spreading depolarization (CSD) has been observed during the early phase of subarachnoid hemorrhage (SAH) in clinical settings, the pathogenicity of CSD is unclear. The aim of this study is to elucidate the effects of loss of membrane potential on neuronal damage during the acute phase of SAH. METHODS Twenty-four rats were subjected to SAH by the perforation method. The propagation of depolarization in the brain cortex was examined by using electrodes to monitor 2 direct-current (DC) potentials and obtaining NADH (reduced nicotinamide adenine dinucleotide) fluorescence images while exposing the parietal-temporal cortex to ultraviolet light. Cerebral blood flow (CBF) was monitored in the vicinity of the lateral electrode. Twenty-four hours after onset of SAH, histological damage was evaluated at the DC potential recording sites. RESULTS Changes in DC potentials (n = 48 in total) were sorted into 3 types according to the appearance of ischemic depolarization in the entire hemisphere following induction of SAH. In Type 1 changes (n = 21), ischemic depolarization was not observed during a 1-hour observation period. In Type 2 changes (n = 13), the DC potential demonstrated ischemic depolarization on initiation of SAH and recovered 80% from the maximal DC deflection during a 1-hour observation period (33.3 ± 15.8 minutes). In Type 3 changes (n = 14), the DC potential displayed ischemic depolarization and did not recover during a 1-hour observation period. Histological evaluations at DC potential recording sites showed intact tissue at all sites in the Type 1 group, whereas in the Type 2 and Type 3 groups neuronal damage of varying severity was observed depending on the duration of ischemic depolarization. The duration of depolarization that causes injury to 50% of neurons (P 50 ) was estimated to be 22.4 minutes (95% confidence intervals 17.0-30.3 minutes). CSD was observed in 3 rats at 6 sites in the Type 1 group 5.1 ± 2.2 minutes after initiation of SAH. On NADH fluorescence images CSD was initially observed in the anterior cortex; it propagated through the entire hemisphere in the direction of the occipital cortex at a rate of 3 mm/minute, with repolarization in 2.3 ± 1.2 minutes. DC potential recording sites that had undergone CSD were found to have intact tissue 24 hours later. Compared with depolarization that caused 50% neuronal damage, the duration of CSD was too short to cause histological damage. CONCLUSIONS CSD was successfully visualized using NADH fluorescence. It propagated from the anterior to the posterior cortex along with an increase in CBF. The duration of depolarization in CSD (2.3 ± 1.2 minutes) was far shorter than that causing 50% neuronal damage (22.4 minutes) and was not associated with histological damage in the current experimental setting.

All-solid-state single longitudinal mode MOPA laser system

NASA Astrophysics Data System (ADS)

Zhang, Xiang; Gu, Haidong; Hu, Wenhua; Ren, Shilong

2018-03-01

Side diode pumped electro-optical Q Switching Nd: YAG is demonstrated as master oscillator. F-P etalon and twisted-mode cavity combined configuration is introduced to select longitudinal modes. The seed light experiences a round trip through the two flash pump amplifiers, in this device, the 4f image transmission system and SBS phase conjugate mirror is adopted in order to improved beam quality, by compensating the heat depolarization effect and eliminate wave-front distortion. In the condition of 1 or 5 repetitions of the wavelength at 1064nm, it produces the pulse energy of 300mJ, pulse width of 12ns, and energy instability (RMS) below 3% in single longitudinal mode operation. With a type two-phase matched KTP crystal, 532nm green light is yielded, at 1 Hz repetition rate, the pulse energy of green light is more than 150mJ.

Infrared light excites cells by changing their electrical capacitance

PubMed Central

Shapiro, Mikhail G.; Homma, Kazuaki; Villarreal, Sebastian; Richter, Claus-Peter; Bezanilla, Francisco

2012-01-01

Optical stimulation has enabled important advances in the study of brain function and other biological processes, and holds promise for medical applications ranging from hearing restoration to cardiac pace making. In particular, pulsed laser stimulation using infrared wavelengths >1.5 μm has therapeutic potential based on its ability to directly stimulate nerves and muscles without any genetic or chemical pre-treatment. However, the mechanism of infrared stimulation has been a mystery, hindering its path to the clinic. Here we show that infrared light excites cells through a novel, highly general electrostatic mechanism. Infrared pulses are absorbed by water, producing a rapid local increase in temperature. This heating reversibly alters the electrical capacitance of the plasma membrane, depolarizing the target cell. This mechanism is fully reversible and requires only the most basic properties of cell membranes. Our findings underscore the generality of pulsed infrared stimulation and its medical potential. PMID:22415827

On the origin of the low-temperature band in depolarization current spectra of poled multicomponent silicate glasses

NASA Astrophysics Data System (ADS)

Brunkov, P. N.; Kaasik, V. P.; Lipovskii, A. A.; Tagantsev, D. K.

2018-04-01

Thermally stimulated depolarization current spectra of poled silicate multicomponent glasses in the vicinity of room temperature (220-320 K) have been recorded and two bands, typical for such glasses, have been observed. It was shown that the high-temperature band (at about 290 K) is related to the relaxation of poled glass structure in the bulk, while the low-temperature band (at about 230-270 K) should be attributed to the surface phenomenon—absorption/desorption of positive species of ambient atmosphere, supposedly, water cluster ions H+(H2O)n.

Iberiotoxin-sensitive and -insensitive BK currents in Purkinje neuron somata

PubMed Central

Benton, Mark D.; Lewis, Amanda H.; Bant, Jason S.

2013-01-01

Purkinje cells have specialized intrinsic ionic conductances that generate high-frequency action potentials. Disruptions of their Ca or Ca-activated K (KCa) currents correlate with altered firing patterns in vitro and impaired motor behavior in vivo. To examine the properties of somatic KCa currents, we recorded voltage-clamped KCa currents in Purkinje cell bodies isolated from postnatal day 17–21 mouse cerebellum. Currents were evoked by endogenous Ca influx with approximately physiological Ca buffering. Purkinje somata expressed voltage-activated, Cd-sensitive KCa currents with iberiotoxin (IBTX)-sensitive (>100 nS) and IBTX-insensitive (>75 nS) components. IBTX-sensitive currents activated and partially inactivated within milliseconds. Rapid, incomplete macroscopic inactivation was also evident during 50- or 100-Hz trains of 1-ms depolarizations. In contrast, IBTX-insensitive currents activated more slowly and did not inactivate. These currents were insensitive to the small- and intermediate-conductance KCa channel blockers apamin, scyllatoxin, UCL1684, bicuculline methiodide, and TRAM-34, but were largely blocked by 1 mM tetraethylammonium. The underlying channels had single-channel conductances of ∼150 pS, suggesting that the currents are carried by IBTX-resistant (β4-containing) large-conductance KCa (BK) channels. IBTX-insensitive currents were nevertheless increased by small-conductance KCa channel agonists EBIO, chlorzoxazone, and CyPPA. During trains of brief depolarizations, IBTX-insensitive currents flowed during interstep intervals, and the accumulation of interstep outward current was enhanced by EBIO. In current clamp, EBIO slowed spiking, especially during depolarizing current injections. The two components of BK current in Purkinje somata likely contribute differently to spike repolarization and firing rate. Moreover, augmentation of BK current may partially underlie the action of EBIO and chlorzoxazone to alleviate disrupted Purkinje cell firing associated with genetic ataxias. PMID:23446695

Optical Polarization of Excitons and Trions Under Continuous and Pulsed Excitation in Single Layers of WSe2

DTIC Science & Technology

2017-10-11

dependence of the depolarization of the trion follows the same trend as that of the neutral exciton and involves collisional broadening. However, the...spectrum of our WSe2 sample, differential reflectivity, power dependence spectra, an alternate fitting scheme, raw helicity analyzed photoluminescence...that with cw excitation, the polarization of the trion is nearly twice the polarization of the neutral exciton at 5 K, and the temperature dependence

PKCɛ mediates substance P inhibition of GABAA receptors-mediated current in rat dorsal root ganglion.

PubMed

Li, Li; Zhao, Lei; Wang, Yang; Ma, Ke-tao; Shi, Wen-yan; Wang, Ying-zi; Si, Jun-qiang

2015-02-01

The mechanism underlying the modulatory effect of substance P (SP) on GABA-activated response in rat dorsal root ganglion (DRG) neurons was investigated. In freshly dissociated rat DRG neurons, whole-cell patch-clamp technique was used to record GABA-activated current and sharp electrode intracellular recording technique was used to record GABA-induced membrane depolarization. Application of GABA (1-1000 μmol/L) induced an inward current in a concentration-dependent manner in 114 out of 127 DRG neurons (89.8 %) examined with whole-cell patch-clamp recordings. Bath application of GABA (1-1000 μmol/L) evoked a depolarizing response in 236 out of 257 (91.8%) DRG neurons examined with intracellular recordings. Application of SP (0.001-1 μmol/L) suppressed the GABA-activated inward current and membrane depolarization. The inhibitory effects were concentration-dependent and could be blocked by the selective neurokinin 1 (NK1) receptors antagonist spantide but not by L659187 and SR142801 (1 μmol/L, n=7), selective antagonists of NK2 and NK3. The inhibitory effect of SP was significantly reduced by the calcium chelator BAPTA-AM, phospholipase C (PLC) inhibitor U73122, and PKC inhibitor chelerythrine, respectively. The PKA inhibitor H-89 did not affect the SP effect. Remarkably, the inhibitory effect of SP on GABA-activated current was nearly completely removed by a selective PKCε inhibitor epilon-V1-2 but not by safingol and LY333531, selective inhibitors of PKCα and PKCβ. Our results suggest that NK1 receptor mediates SP-induced inhibition of GABA-activated current and membrane depolarization by activating intracellular PLC-Ca²⁺-PKCε cascade. SP might regulate the excitability of peripheral nociceptors through inhibition of the "pre-synaptic inhibition" evoked by GABA, which may explain its role in pain and neurogenic inflammation.

Carvacrol modulates voltage-gated sodium channels kinetics in dorsal root ganglia.

PubMed

Joca, Humberto Cavalcante; Vieira, Daiana Cardoso Oliveira; Vasconcelos, Aliny Perreira; Araújo, Demetrius Antônio Machado; Cruz, Jader Santos

2015-06-05

Recent studies have shown that many of plant-derived compounds interact with specific ion channels and thereby modulate many sensing mechanisms, such as nociception. The monoterpenoid carvacrol (5-isopropyl-2-methylphenol) has an anti-nociceptive effect related to a reduction in neuronal excitability and voltage-gated Na(+) channels (NaV) inhibition in peripheral neurons. However, the detailed mechanisms of carvacrol-induced inhibition of neuronal NaV remain elusive. This study explores the interaction between carvacrol and NaV in isolated dorsal root ganglia neurons. Carvacrol reduced the total voltage-gated Na(+) current and tetrodotoxin-resistant (TTX-R) Na(+) current component in a concentration-dependent manner. Carvacrol accelerates current inactivation and induced a negative-shift in voltage-dependence of steady-state fast inactivation in total and TTX-R Na(+) current. Furthermore, carvacrol slowed the recovery from inactivation. Carvacrol provoked a leftward shift in both the voltage-dependence of steady-state inactivation and activation of the TTX-R Na(+) current component. In addition, carvacrol-induced inhibition of TTX-R Na(+) current was enhanced by an increase in stimulation frequency and when neurons were pre-conditioned with long depolarization pulse (5s at -50 mV). Taken all results together, we herein demonstrated that carvacrol affects NaV gating properties. The present findings would help to explain the mechanisms underlying the analgesic activity of carvacrol. Copyright © 2015 Elsevier B.V. All rights reserved.

Presynaptic miniature GABAergic currents in developing interneurons.

PubMed

Trigo, Federico F; Bouhours, Brice; Rostaing, Philippe; Papageorgiou, George; Corrie, John E T; Triller, Antoine; Ogden, David; Marty, Alain

2010-04-29

Miniature synaptic currents have long been known to represent random transmitter release under resting conditions, but much remains to be learned about their nature and function in central synapses. In this work, we describe a new class of miniature currents ("preminis") that arise by the autocrine activation of axonal receptors following random vesicular release. Preminis are prominent in gabaergic synapses made by cerebellar interneurons during the development of the molecular layer. Unlike ordinary miniature postsynaptic currents in the same cells, premini frequencies are strongly enhanced by subthreshold depolarization, suggesting that the membrane depolarization they produce belongs to a feedback loop regulating neurotransmitter release. Thus, preminis could guide the formation of the interneuron network by enhancing neurotransmitter release at recently formed synaptic contacts. Copyright 2010 Elsevier Inc. All rights reserved.

Enhanced excitatory input to melanin concentrating hormone neurons during developmental period of high food intake is mediated by GABA.

PubMed

Li, Ying; van den Pol, Anthony N

2009-12-02

In contrast to the local axons of GABA neurons of the cortex and hippocampus, lateral hypothalamic neurons containing melanin concentrating hormone (MCH) and GABA send long axons throughout the brain and play key roles in energy homeostasis and mental status. In adults, MCH neurons maintain a hyperpolarized membrane potential and most of the synaptic input is inhibitory. In contrast, we found that developing MCH neurons received substantially more excitatory synaptic input. Based on gramicidin-perforated patch recordings in hypothalamic slices from MCH-green fluorescent protein transgenic mice, we found that GABA was the primary excitatory synaptic transmitter in embryonic and neonatal ages up to postnatal day 10. Surprisingly, glutamate assumed only a minor excitatory role, if any. GABA plays a complex role in developing MCH neurons, with its actions conditionally dependent on a number of factors. GABA depolarization could lead to an increase in spikes either independently or in summation with other depolarizing stimuli, or alternately, depending on the relative timing of other depolarizing events, could lead to shunting inhibition. The developmental shift from depolarizing to hyperpolarizing occurred later in the dendrites than in the cell body. Early GABA depolarization was based on a Cl(-)-dependent inward current. An interesting secondary depolarization in mature neurons that followed an initial hyperpolarization was based on a bicarbonate mechanism. Thus during the early developmental period when food consumption is high, MCH neurons are more depolarized than in the adult, and an increased level of excitatory synaptic input to these orexigenic cells is mediated by GABA.

Enhanced excitatory input to MCH neurons during developmental period of high food intake is mediated by GABA

PubMed Central

Li, Ying; van den Pol, Anthony N.

2010-01-01

In contrast to the local axons of GABA neurons of the cortex and hippocampus, lateral hypothalamic neurons containing melanin concentrating hormone (MCH) and GABA send long axons throughout the brain and play key roles in energy homeostasis and mental status. In adults, MCH neurons maintain a hyperpolarized membrane potential and most of the synaptic input is inhibitory. In contrast, we found that developing MCH neurons received substantially more excitatory synaptic input. Based on gramicidicin-perforated patch recordings in hypothalamic slices from MCH-GFP transgenic mice, we found that GABA was the primary excitatory synaptic transmitter in embryonic and neonatal ages up to postnatal day 10. Surprisingly, glutamate assumed only a minor excitatory role, if any. GABA plays a complex role in developing MCH neurons, with its actions conditionally dependent on a number of factors. GABA depolarization could lead to an increase in spikes either independently or in summation with other depolarizing stimuli, or alternately, depending on the relative timing of other depolarizing events, could lead to shunting inhibition. The developmental shift from depolarizing to hyperpolarizing occurred later in the dendrites than in the cell body. Early GABA depolarization was based on a Cl− dependent inward current. An interesting secondary depolarization in mature neurons that followed an initial hyperpolarization was based on a bicarbonate mechanism. Thus during the early developmental period when food consumption is high, MCH neurons are more depolarized than in the adult, and an increased level of excitatory synaptic input to these orexigenic cells is mediated by GABA. PMID:19955372

Optical diagnosis of dengue virus infected human blood using Mueller matrix polarimetry

NASA Astrophysics Data System (ADS)

Anwar, Shahzad; Firdous, Shamaraz

2016-08-01

Currently dengue fever diagnosis methods include capture ELISAs, immunofluorescence tests, and hemagglutination assays. In this study optical diagnosis of dengue virus infection in the whole blood is presented utilizing Mueller matrix polarimetry. Mueller matrices of about 50 dengue viral infected and 25 non-dengue healthy blood samples were recorded utilizing light source from 500 to 700 nm with scanning step of 10 nm. Polar decomposition of the Mueller matrices for all the blood samples was performed that yielded polarization properties including depolarization, diattenuation, degree of polarization, retardance and optical activity, out of which, depolarization index clusters up the diseased and healthy in to different separate groups. The average depolarized light in the case of dengue infection in the whole blood at 500 nm is 18%, whereas for the healthy blood samples it is 13.5%. This suggests that depolarization index of polarized light at the wavelengths of 500, 510, 520, 530 and 540 nm, we find that in case of depolarization index values are higher for dengue viral infection as compared to normal samples. This technique can effectively be used for the characterization of the dengue virus infected at an early stage of disease.

The Mechanism of Extracellular Stimulation of Nerve Cells on an Electrolyte-Oxide-Semiconductor Capacitor

PubMed Central

Schoen, Ingmar; Fromherz, Peter

2007-01-01

Extracellular excitation of neurons is applied in studies of cultured networks and brain tissue, as well as in neuroprosthetics. We elucidate its mechanism in an electrophysiological approach by comparing voltage-clamp and current-clamp recordings of individual neurons on an insulated planar electrode. Noninvasive stimulation of neurons from pedal ganglia of Lymnaea stagnalis is achieved by defined voltage ramps applied to an electrolyte/HfO2/silicon capacitor. Effects on the smaller attached cell membrane and the larger free membrane are distinguished in a two-domain-stimulation model. Under current-clamp, we study the polarization that is induced for closed ion channels. Under voltage-clamp, we determine the capacitive gating of ion channels in the attached membrane by falling voltage ramps and for comparison also the gating of all channels by conventional variation of the intracellular voltage. Neuronal excitation is elicited under current-clamp by two mechanisms: Rising voltage ramps depolarize the free membrane such that an action potential is triggered. Falling voltage ramps depolarize the attached membrane such that local ion currents are activated that depolarize the free membrane and trigger an action potential. The electrophysiological analysis of extracellular stimulation in the simple model system is a basis for its systematic optimization in neuronal networks and brain tissue. PMID:17098803

Glucose is necessary to maintain neurotransmitter homeostasis during synaptic activity in cultured glutamatergic neurons.

PubMed

Bak, Lasse K; Schousboe, Arne; Sonnewald, Ursula; Waagepetersen, Helle S

2006-10-01

Glucose is the primary energy substrate for the adult mammalian brain. However, lactate produced within the brain might be able to serve this purpose in neurons. In the present study, the relative significance of glucose and lactate as substrates to maintain neurotransmitter homeostasis was investigated. Cultured cerebellar (primarily glutamatergic) neurons were superfused in medium containing [U-13C]glucose (2.5 mmol/L) and lactate (1 or 5 mmol/L) or glucose (2.5 mmol/L) and [U-13C]lactate (1 mmol/L), and exposed to pulses of N-methyl-D-aspartate (300 micromol/L), leading to synaptic activity including vesicular release. The incorporation of 13C label into intracellular lactate, alanine, succinate, glutamate, and aspartate was determined by mass spectrometry. The metabolism of [U-13C]lactate under non-depolarizing conditions was high compared with that of [U-13C]glucose; however, it decreased significantly during induced depolarization. In contrast, at both concentrations of extracellular lactate, the metabolism of [U-13C]glucose was increased during neuronal depolarization. The role of glucose and lactate as energy substrates during vesicular release as well as transporter-mediated influx and efflux of glutamate was examined using preloaded D-[3H]aspartate as a glutamate tracer and DL-threo-beta-benzyloxyaspartate to inhibit glutamate transporters. The results suggest that glucose is essential to prevent depolarization-induced reversal of the transporter (efflux), whereas vesicular release was unaffected by the choice of substrate. In conclusion, the present study shows that glucose is a necessary substrate to maintain neurotransmitter homeostasis during synaptic activity and that synaptic activity does not induce an upregulation of lactate metabolism in glutamatergic neurons.

Rheology of biological macromolecules

NASA Astrophysics Data System (ADS)

Ariyaratne, Amila Dinesh

Proteins have interesting mechanical properties in addition to the remarkable functionality. For example, Guanylate kinase is an enzyme that catalyzes Guano- sine monophosphate (GMP) to Guanosine diphosphate (GDP) conversion and this enzyme is approximately 5 nm in size. A gold nano particle of similar size shows linear elasticity for strains up to ˜ 0.1% and shows plastic deformation beyond that, whereas the enzyme Guanylate kinase can have strains up to 1 % with reversible deformation. Our experiments show many different regimes of the mechanical response before the plastic deformation of these proteins. In this dissertation, I study the materials properties of two classes of proteins, an ion channel protein and a transferase, which is a globular protein. The experimental techniques to study the materials properties of these proteins were uniquely developed at the Zocchi lab. Therefore, we were able to observe previously unknown characteristics of these folded proteins. The mechanical properties of the voltage gated potassium channel KvAP was studied by applying AC depolarizing voltages. This technique gave new information about the system that was not seen in the previous studies. These previous experiments were based on applying DC depolarizing voltage steps across the membrane to study the ionic current. By monitoring the ionic current at different depolarizing voltage steps, the DC gating process of the channel could be under- stood. We probed the channel using AC depolarizing signals instead of DC pulses and the ionic current revealed new behaviors, which cannot be predicted with the DC response. We found that the conformational motion of the voltage sensing domain of the ion channel shows internal dissipation. Further, a new non linearity in the dissipation parameter was found in which the dissipation parameter increased with the shear rate of the applied force. Previous studies at the Zocchi lab used a nano rheology experiment on the protein Guanylate kinase to study the mechanical properties of a globular protein. The protein was subjected to a mechanical force and the deformation was measured with sub-Angstrom resolution. We found that the protein shows a linear elasticity regime for low forcing and viscoelastic behavior for high forcing. The internal viscosity of the protein is due to the internal dissipation of the protein. This dissertation takes the work on nano rheology of proteins further by studying the temperature effect on the materials properties of the protein and the contribution of the surface of the protein to the observed mechanics. In addition to studying the materials properties of proteins, we used proteins to design new biomimetic systems. The first system covered in this dissertation is the development of a novel sensor platform for molecules. In this sensor, we detect the change in the stiffness of the substrate upon binding a target rather than the usual scheme of detecting the change in mass upon binding of a target. By combining the nano rheology setup with localized surface plasmon resonance, this sensor platform yields a very robust signal. The other biomimetic system that is discussed here is an artificial axon is constructed with ion channels and lipid bilayers.

Escitalopram block of hERG potassium channels.

PubMed

Chae, Yun Ju; Jeon, Ji Hyun; Lee, Hong Joon; Kim, In-Beom; Choi, Jin-Sung; Sung, Ki-Wug; Hahn, Sang June

2014-01-01

Escitalopram, a selective serotonin reuptake inhibitor, is the pharmacologically active S-enantiomer of the racemic mixture of RS-citalopram and is widely used in the treatment of depression. The effects of escitalopram and citalopram on the human ether-a-go-go-related gene (hERG) channels expressed in human embryonic kidney cells were investigated using voltage-clamp and Western blot analyses. Both drugs blocked hERG currents in a concentration-dependent manner with an IC50 value of 2.6 μM for escitalopram and an IC50 value of 3.2 μM for citalopram. The blocking of hERG by escitalopram was voltage-dependent, with a steep increase across the voltage range of channel activation. However, voltage independence was observed over the full range of activation. The blocking by escitalopram was frequency dependent. A rapid application of escitalopram induced a rapid and reversible blocking of the tail current of hERG. The extent of the blocking by escitalopram during the depolarizing pulse was less than that during the repolarizing pulse, suggesting that escitalopram has a high affinity for the open state of the hERG channel, with a relatively lower affinity for the inactivated state. Both escitalopram and citalopram produced a reduction of hERG channel protein trafficking to the plasma membrane but did not affect the short-term internalization of the hERG channel. These results suggest that escitalopram blocked hERG currents at a supratherapeutic concentration and that it did so by preferentially binding to both the open and the inactivated states of the channels and by inhibiting the trafficking of hERG channel protein to the plasma membrane.

Dielectric relaxation of 2-ethyl-1-hexanol around the glass transition by thermally stimulated depolarization currents.

PubMed

Arrese-Igor, S; Alegría, A; Colmenero, J

2015-06-07

We explore new routes for characterizing the Debye-like and α relaxation in 2-ethyl-1-hexanol (2E1H) monoalcohol by using low frequency dielectric techniques including thermally stimulated depolarization current (TSDC) techniques and isothermal depolarization current methods. In this way, we have improved the resolution of the overlapped processes making it possible the analysis of the data in terms of a mode composition as expected for a chain-like response. Furthermore the explored ultralow frequencies enabled to study dynamics at relatively low temperatures close to the glass transition (Tg). Results show, on the one hand, that Debye-like and α relaxation timescales dramatically approach to each other upon decreasing temperature to Tg. On the other hand, the analysis of partial polarization TSDC data confirms the single exponential character of the Debye-like relaxation in 2E1H and rules out the presence of Rouse type modes in the scenario of a chain-like response. Finally, on crossing the glass transition, the Debye-like relaxation shows non-equilibrium effects which are further emphasized by aging treatment and would presumably emerge as a result of the arrest of the structural relaxation below Tg.

The effects of deoxyelephantopin on the cardiac delayed rectifier potassium channel current (IKr) and human ether-a-go-go-related gene (hERG) expression.

PubMed

Teah, Yi Fan; Abduraman, Muhammad Asyraf; Amanah, Azimah; Adenan, Mohd Ilham; Sulaiman, Shaida Fariza; Tan, Mei Lan

2017-09-01

Elephantopus scaber Linn and its major bioactive component, deoxyelephantopin are known for their medicinal properties and are often reported to have various cytotoxic and antitumor activities. This plant is widely used as folk medicine for a plethora of indications although its safety profile remains unknown. Human ether-a-go-go-related gene (hERG) encodes the cardiac I Kr current which is a determinant of the duration of ventricular action potentials and QT interval. The hERG potassium channel is an important antitarget in cardiotoxicity evaluation. This study investigated the effects of deoxyelephantopin on the current, mRNA and protein expression of hERG channel in hERG-transfected HEK293 cells. The hERG tail currents following depolarization pulses were insignificantly affected by deoxyelephantopin in the transfected cell line. Current reduction was less than 40% as compared with baseline at the highest concentration of 50 μM. The results were consistent with the molecular docking simulation and hERG surface protein expression. Interestingly, it does not affect the hERG expression at both transcriptional and translational level at most concentrations, although higher concentration at 10 μM caused protein accumulation. In conclusion, deoxyelephantopin is unlikely a clinically significant hERG channel and I kr blocker. Copyright © 2017 Elsevier Ltd. All rights reserved.

Calcium currents in a fast-twitch skeletal muscle of the rat.

PubMed

Donaldson, P L; Beam, K G

1983-10-01

Slow ionic currents were measured in the rat omohyoid muscle with the three-microelectrode voltage-clamp technique. Sodium and delayed rectifier potassium currents were blocked pharmacologically. Under these conditions, depolarizing test pulses elicited an early outward current, followed by a transient slow inward current, followed in turn by a late outward current. The early outward current appeared to be a residual delayed rectifier current. The slow inward current was identified as a calcium current on the basis that (a) its magnitude depended on extracellular calcium concentration, (b) it was blocked by the addition of the divalent cations cadmium or nickel, and reduced in magnitude by the addition of manganese or cobalt, and (c) barium was able to replace calcium as an inward current carrier. The threshold potential for inward calcium current was around -20 mV in 10mM extracellular calcium and about -35 mV in 2 mM calcium. Currents were net inward over part of their time course for potentials up to at least +30 mV. At temperatures of 20-26 degrees C, the peak inward current (at approximately 0 mV) was 139 +/- 14 microA/cm2 (mean +/- SD), increasing to 226 +/- 28 microA/cm2 at temperatures of 27-37 degrees C. The late outward current exhibited considerable fiber-to-fiber variability. In some fibers it was primarily a time-independent, nonlinear leakage current. In other fibers it was primarily a time-independent, nonlinear leakage current. In other fibers it appeared to be the sum of both leak and a slowly activated outward current. The rate of activation of inward calcium current was strongly temperature dependent. For example, in a representative fiber, the time-to-peak inward current for a +10-mV test pulse decreased from approximately 250 ms at 20 degrees C to 100 ms at 30 degrees C. At 37 degrees C, the time-to-peak current was typically approximately 25 ms. The earliest phase of activation was difficult to quantify because the ionic current was partially obscured by nonlinear charge movement. Nonetheless, at physiological temperatures, the rate of calcium channel activation in rat skeletal muscle is about five times faster than activation of calcium channels in frog muscle. This pathway may be an important source of calcium entry in mammalian muscle.

TMEM16A Channels Contribute to the Myogenic Response in Cerebral Arteries

PubMed Central

Bulley, Simon; Neeb, Zachary P.; Burris, Sarah K.; Bannister, John P.; Thomas-Gatewood, Candice M.; Jangsangthong, Wanchana; Jaggar, Jonathan H.

2013-01-01

Rationale Pressure-induced arterial depolarization and constriction (the myogenic response), is a smooth muscle cell (myocyte)-specific mechanism that controls regional organ blood flow and systemic blood pressure. Several different non-selective cation channels contribute to pressure-induced depolarization, but signaling mechanisms involved are unclear. Similarly uncertain is the contribution of anion channels to the myogenic response and physiological functions and mechanisms of regulation of recently discovered transmembrane 16A (TMEM16A) chloride (Cl−) channels in arterial myocytes. Objective Investigate the hypothesis that myocyte TMEM16A channels control membrane potential and contractility and contribute to the myogenic response in cerebral arteries. Methods and Results Cell swelling induced by hyposmotic bath solution stimulated Cl− currents in arterial myocytes that were blocked by TMEM16A channel inhibitory antibodies, RNAi-mediated selective TMEM16A channel knockdown, removal of extracellular calcium (Ca2+), replacement of intracellular EGTA with BAPTA, a fast Ca2+ chelator, and Gd3+ and SKF-96365, non-selective cation channel blockers. In contrast, nimodipine, a voltage-dependent Ca2+ channel inhibitor, or thapsigargin, which depletes intracellular Ca2+ stores, did not alter swelling-activated TMEM16A currents. Pressure (−40 mmHg)-induced membrane stretch activated ion channels in arterial myocyte cell-attached patches that were inhibited by TMEM16A antibodies and were of similar amplitude to recombinant TMEM16A channels. TMEM16A knockdown reduced intravascular pressure-induced depolarization and vasoconstriction, but did not alter depolarization (60 mmol/L K+)-induced vasoconstriction. Conclusions Membrane stretch activates arterial myocyte TMEM16A channels, leading to membrane depolarization and vasoconstriction. Data also provide a mechanism by which a local Ca2+ signal generated by non-selective cation channels stimulates TMEM16A channels to induce myogenic constriction. PMID:22872152

Increase in cytosolic Ca2+ produced by hypoxia and other depolarizing stimuli activates a non-selective cation channel in chemoreceptor cells of rat carotid body

PubMed Central

Kang, Dawon; Wang, Jiaju; Hogan, James O; Vennekens, Rudi; Freichel, Marc; White, Carl; Kim, Donghee

2014-01-01

The current model of O2 sensing by carotid body chemoreceptor (glomus) cells is that hypoxia inhibits the outward K+ current and causes cell depolarization, Ca2+ influx via voltage-dependent Ca2+ channels and a rise in intracellular [Ca2+] ([Ca2+]i). Here we show that hypoxia (<5% O2), in addition to inhibiting the two-pore domain K+ channels TASK-1/3 (TASK), indirectly activates an ∼20 pS channel in isolated glomus cells. The 20 pS channel was permeable to K+, Na+ and Cs+ but not to Cl− or Ca2+. The 20 pS channel was not sensitive to voltage. Inhibition of TASK by external acid, depolarization of glomus cells with high external KCl (20 mm) or opening of the Ca2+ channel with FPL64176 activated the 20 pS channel when 1 mm Ca2+ was present in the external solution. Ca2+ (10 μm) applied to the cytosolic side of inside-out patches activated the 20 pS channel. The threshold [Ca2+]i for activation of the 20 pS channel in cell-attached patches was ∼200 nm. The reversal potential of the 20 pS channel was estimated to be −28 mV. Our results reveal a sequential mechanism in which hypoxia (<5% O2) first inhibits the K+ conductance and then activates a Na+-permeable, non-selective cation channel via depolarization-induced rise in [Ca2+]i. Our results suggest that inhibition of K+ efflux and stimulation of Na+ influx both contribute to the depolarization of glomus cells during moderate to severe hypoxia. PMID:24591572

Isoflurane depolarizes bronchopulmonary C neurons by inhibiting transient A-type and delayed rectifier potassium channels.

PubMed

Zhang, Zhenxiong; Zhuang, Jianguo; Zhang, Cancan; Xu, Fadi

2013-04-01

Inhalation of isoflurane (ISO), a widely used volatile anesthetic, can produce clinical tachypnea. In dogs, this response is reportedly mediated by bronchopulmonary C-fibers (PCFs), but the relevant mechanisms remain unclear. Activation of transient A-type potassium current (IA) channels and delayed rectifier potassium current (IK) channels hyperpolarizes neurons, and inhibition of both channels by ISO increases neural firing. Due to the presence of these channels in the cell bodies of rat PCFs, we determined whether ISO could stimulate PCFs to produce tachypnea in anesthetized rats, and, if so, whether this response resulted from ISO-induced depolarization of the pulmonary C neurons via the inhibition of IA and IK. We recorded ventilatory responses to 5% ISO exposure in anesthetized rats before and after blocking PCF conduction and the responses of pulmonary C neurons (extracellularly recorded) to ISO exposure. ISO-induced (1mM) changes in pulmonary C neuron membrane potential and IA/IK were tested using the perforated patch clamp technique. We found that: (1) ISO inhalation evoked a brief tachypnea (∼7s) and that this response disappeared after blocking PCF conduction; (2) the ISO significantly elevated (by 138%) the firing rate of most pulmonary C neurons (17 out of 21) in the nodose ganglion; and (3) ISO perfusion depolarized the pulmonary C neurons in the vitro and inhibited both IA and IK, and this evoked-depolarization was largely diminished after blocking both IA and IK. Our results suggest that ISO is able to stimulate PCFs to elicit tachypnea in rats, at least partly, via inhibiting IA and IK, thereby depolarizing the pulmonary C neurons. Copyright © 2013. Published by Elsevier B.V.

Postnatal changes in somatic gamma-aminobutyric acid signalling in the rat hippocampus.

PubMed

Tyzio, Roman; Minlebaev, Marat; Rheims, Sylvain; Ivanov, Anton; Jorquera, Isabelle; Holmes, Gregory L; Zilberter, Yuri; Ben-Ari, Yehezkiel; Khazipov, Rustem

2008-05-01

During postnatal development of the rat hippocampus, gamma-aminobutyric acid (GABA) switches its action on CA3 pyramidal cells from excitatory to inhibitory. To characterize the underlying changes in the GABA reversal potential, we used somatic cell-attached recordings of GABA(A) and N-methyl-D-aspartate channels to monitor the GABA driving force and resting membrane potential, respectively. We found that the GABA driving force is strongly depolarizing during the first postnatal week. The strength of this depolarization rapidly declines with age, although GABA remains slightly depolarizing, by a few millivolts, even in adult neurons. Reduction in the depolarizing GABA driving force was due to a progressive negative shift of the reversal potential of GABA currents. Similar postnatal changes in GABA signalling were also observed using the superfused hippocampus preparation in vivo, and in the hippocampal interneurons in vitro. We also found that in adult pyramidal cells, somatic GABA reversal potential is maintained at a slightly depolarizing level by bicarbonate conductance, chloride-extrusion and chloride-loading systems. Thus, the postnatal excitatory-to-inhibitory switch in somatic GABA signalling is associated with a negative shift of the GABA reversal potential but without a hyperpolarizing switch in the polarity of GABA responses. These results also suggest that in adult CA3 pyramidal cells, somatic GABAergic inhibition takes place essentially through shunting rather than hyperpolarization. Apparent hyperpolarizing GABA responses previously reported in the soma of CA3 pyramidal cells are probably due to cell depolarization during intracellular or whole-cell recordings.

Effect of Temperature on Formation and Stability of Shallow Trap at a Dielectric Interface of the Multilayer

NASA Astrophysics Data System (ADS)

Rogti, F.

2015-12-01

Space-charge behavior at dielectric interfaces in multilayer low-density polyethylene (LDPE) and fluorinated ethylene propylene (FEP) subjected to a direct-current (DC) field has been investigated as a function of temperature using the pulsed electroacoustic technique. A sandwich structure constituted by two nonidentical LDPE/FEP dielectric films was used to study the charging propensity of electrode/dielectric and dielectric/dielectric interfaces. The time dependence of the space-charge distribution was subsequently recorded at four temperatures, 20°C, 25°C, 40°C, and 60°C, under field (polarization) and short-circuit (depolarization) conditions. The experimental results demonstrate that temperature plays a significant role in the space-charge dynamics at the dielectric interface. It affects the charge injection, increases the charge mobility and electrical conductivity, and increases the density of shallow traps and trap filling. It is found that traps formed during polarization at high temperature do not remain stable after complete discharge of the multidielectric structure and when poled at low temperatures.

Facilitated giga-seal formation with a just originated glass surface.

PubMed

Böhle, T; Benndorf, K

1994-07-01

A simple technique of tip preparation in patch pipettes is described, which facilitates giga-seal formation. The pipettes were fabricated from thick-walled borosilicate glass tubing (external diameter 2.0 mm, internal diameter 0.5 mm) and the tips could be repeatedly broken in the bath. The pipette resistance correspondingly fell in steps of 3-20 M omega from about 80 M omega to about 2 M omega (double concentrated Tyrode). Scanning electron microscopy showed that the tip obtained after breaking was fairly plain. These broken tips were especially appropriate for patch-clamping. In cardiac myocytes in 11 out of 26 patches with Na+ channel activity, giga-seals developed spontaneously, i.e. without suction. In these patches the amplitude of the mean current with depolarizing pulses to -40 mV was significantly higher in comparison with patches formed under negative pressure. It is concluded that spontaneously sealed patches are most likely of planar configuration and the Na+ channel activity exceeds that in suction-induced patches.

Axonal Dysfunction Precedes Motor Neuronal Death in Amyotrophic Lateral Sclerosis

PubMed Central

Iwai, Yuta; Shibuya, Kazumoto; Misawa, Sonoko; Sekiguchi, Yukari; Watanabe, Keisuke; Amino, Hiroshi; Kuwabara, Satoshi

2016-01-01

Wide-spread fasciculations are a characteristic feature in amyotrophic lateral sclerosis (ALS), suggesting motor axonal hyperexcitability. Previous excitability studies have shown increased nodal persistent sodium conductances and decreased potassium currents in motor axons of ALS patients, both of the changes inducing hyperexcitability. Altered axonal excitability potentially contributes to motor neuron death in ALS, but the relationship of the extent of motor neuronal death and abnormal excitability has not been fully elucidated. We performed multiple nerve excitability measurements in the median nerve at the wrist of 140 ALS patients and analyzed the relationship of compound muscle action potential (CMAP) amplitude (index of motor neuronal loss) and excitability indices, such as strength-duration time constant, threshold electrotonus, recovery cycle and current-threshold relationships. Compared to age-matched normal controls (n = 44), ALS patients (n = 140) had longer strength-duration time constant (SDTC: a measure of nodal persistent sodium current; p < 0.05), greater threshold changes in depolarizing threshold electrotonus (p < 0.05) and depolarizing current threshold relationship (i.e. less accommodation; (p < 0.05), greater superexcitability (a measure of fast potassium current; p < 0.05) and reduced late subexcitability (a measure of slow potassium current; p < 0.05), suggesting increased persistent sodium currents and decreased potassium currents. The reduced potassium currents were found even in the patient subgroups with normal CMAP (> 5mV). Regression analyses showed that SDTC (R = -0.22) and depolarizing threshold electrotonus (R = -0.22) increased with CMAP decline. These findings suggest that motor nerve hyperexcitability occurs in the early stage of the disease, and precedes motor neuronal loss in ALS. Modulation of altered ion channel function could be a treatment option for ALS. PMID:27383069

Voltage Gating of Shaker K+ Channels

PubMed Central

Rodríguez, Beatriz M.; Sigg, Daniel; Bezanilla, Francisco

1998-01-01

Ionic (Ii) and gating currents (Ig) from noninactivating Shaker H4 K+ channels were recorded with the cut-open oocyte voltage clamp and macropatch techniques. Steady state and kinetic properties were studied in the temperature range 2–22°C. The time course of Ii elicited by large depolarizations consists of an initial delay followed by an exponential rise with two kinetic components. The main Ii component is highly temperature dependent (Q10 > 4) and mildly voltage dependent, having a valence times the fraction of electric field (z) of 0.2–0.3 eo. The Ig On response obtained between −60 and 20 mV consists of a rising phase followed by a decay with fast and slow kinetic components. The main Ig component of decay is highly temperature dependent (Q10 > 4) and has a z between 1.6 and 2.8 eo in the voltage range from −60 to −10 mV, and ∼0.45 eo at more depolarized potentials. After a pulse to 0 mV, a variable recovery period at −50 mV reactivates the gating charge with a high temperature dependence (Q10 > 4). In contrast, the reactivation occurring between −90 and −50 mV has a Q10 = 1.2. Fluctuation analysis of ionic currents reveals that the open probability decreases 20% between 18 and 8°C and the unitary conductance has a low temperature dependence with a Q10 of 1.44. Plots of conductance and gating charge displacement are displaced to the left along the voltage axis when the temperature is decreased. The temperature data suggests that activation consists of a series of early steps with low enthalpic and negative entropic changes, followed by at least one step with high enthalpic and positive entropic changes, leading to final transition to the open state, which has a negative entropic change. PMID:9689029

Modeling and measurement of vesicle pools at the cone ribbon synapse: changes in release probability are solely responsible for voltage-dependent changes in release

PubMed Central

Thoreson, Wallace B.; Van Hook, Matthew J.; Parmelee, Caitlyn; Curto, Carina

2015-01-01

Post-synaptic responses are a product of quantal amplitude (Q), size of the releasable vesicle pool (N), and release probability (P). Voltage-dependent changes in presynaptic Ca2+ entry alter post-synaptic responses primarily by changing P but have also been shown to influence N. With simultaneous whole cell recordings from cone photoreceptors and horizontal cells in tiger salamander retinal slices, we measured N and P at cone ribbon synapses by using a train of depolarizing pulses to stimulate release and deplete the pool. We developed an analytical model that calculates the total pool size contributing to release under different stimulus conditions by taking into account the prior history of release and empirically-determined properties of replenishment. The model provided a formula that calculates vesicle pool size from measurements of the initial post-synaptic response and limiting rate of release evoked by a train of pulses, the fraction of release sites available for replenishment, and the time constant for replenishment. Results of the model showed that weak and strong depolarizing stimuli evoked release with differing probabilities but the same size vesicle pool. Enhancing intraterminal Ca2+ spread by lowering Ca2+ buffering or applying BayK8644 did not increase PSCs evoked with strong test steps showing there is a fixed upper limit to pool size. Together, these results suggest that light-evoked changes in cone membrane potential alter synaptic release solely by changing release probability. PMID:26541100

A role for intracellular zinc in glioma alteration of neuronal chloride equilibrium

PubMed Central

Di Angelantonio, S; Murana, E; Cocco, S; Scala, F; Bertollini, C; Molinari, M G; Lauro, C; Bregestovski, P; Limatola, C; Ragozzino, D

2014-01-01

Glioma patients commonly suffer from epileptic seizures. However, the mechanisms of glioma-associated epilepsy are far to be completely understood. Using glioma-neurons co-cultures, we found that tumor cells are able to deeply influence neuronal chloride homeostasis, by depolarizing the reversal potential of γ-aminobutyric acid (GABA)-evoked currents (EGABA). EGABA depolarizing shift is due to zinc-dependent reduction of neuronal KCC2 activity and requires glutamate release from glioma cells. Consistently, intracellular zinc loading rapidly depolarizes EGABA in mouse hippocampal neurons, through the Src/Trk pathway and this effect is promptly reverted upon zinc chelation. This study provides a possible molecular mechanism linking glioma invasion to excitation/inhibition imbalance and epileptic seizures, through the zinc–mediated disruption of neuronal chloride homeostasis. PMID:25356870

[Ionic mechanisms of depolarization responses induced by glutamate application to nerve cells of Helix pomatia].

PubMed

Gerasimov, V D

1982-01-01

The reversal potentials for transmembrane ionic currents induced by glutamate were measured in different D-neurons of the snail Helix pomatia. The first group of neurons had a mean reversal potential--10.6 +/- 1.2 mV and the second one--40.0 +/- 0.6 mV. Under normal conditions glutamate evoked spike discharges in the first group of neurons but not in the second one. At higher concentrations of glutamate the amplitude of D-responses in the latter group increased only to a certain level, not reaching the critical level for cell firing. Decrease in external Cl concentration led to a shift of their reversal potential in depolarizing direction. Ionic mechanisms of depolarizing responses induced by glutamate in these groups of neurons are discussed.

Lidar measurements of boundary layer depolarization and CCSEM-EDX compositional analysis of airborne particles on collocated passive samplers throughout the forest canopy during the 2016 airborne pollen season at UMBS, Pellston, MI

NASA Astrophysics Data System (ADS)

Wozniak, M. C.; Steiner, A.; Ault, A. P.; Kort, E. A.; Lersch, T.; Casuccio, G.

2017-12-01

Observations of airborne pollen are typically made with volumetric samplers that obtain a time-averaged pollen concentration at a single point. While spatial variations in surface pollen concentrations may be known with these samplers given multiple sampling sites, real-time boundary layer transport of pollen grains cannot be determined except by particle dispersion or tracer transport models. Recently, light detection and ranging (lidar) techniques, such as depolarization, have been used to measure pollen transport and optical properties throughout the boundary layer over time. Here, we use a ground-based micro-pulse lidar (MPL) to observe boundary layer vertical profiles before, during and after the peak anemophilous (wind-driven) pollen season. The lidar depolarization ratio is measured in tandem with the normalized R-squared backscatter (NRB) intensity to determine the contribution of aspherical particles to the scatterers present throughout the boundary layer. Measurements are taken from April 15 - July 12, 2016 at the University of Michigan Biological Station (UMBS) PROPHET outdoor research lab and tower within a largely forested region. UMBS is dominated by Acer rubrum, Betula papyrifera, Pinus resinosa, Quercus rubra and Pinus strobus, all of which began flowering on 4/19, 5/3, 5/25, 5/25 and 6/14, respectively. Temperature, relative humidity and wind speed measured on site determine daytime conditions conducive to pollen dispersion from flowers. Lidar depolarization ratios between 0.08-0.14 and higher are observed in the daytime boundary layer on days shortly after the flowering dates of the aforementioned species, elevated above the background level of 0.06 or less. Lidar observations are supplemented with aerosol compositional analysis determined by computer-controlled scanning electron microscopy and energy-dispersive X-ray spectroscopy (CCSEM-EDX) on passive sampler data from below, within and above the forest canopy at PROPHET tower. Particles are separated into the following classes based on composition: pollen, non-pollen biological, soot and other (including mineral dust). Particle shape parameters such as aspect ratio and circularity determined from CCSEM images to estimate how aspherical, and thus how strongly depolarizing, each particle class is.

Study of resonance light scattering for remote optical probing

NASA Technical Reports Server (NTRS)

Penney, C. M.; Morey, W. W.; St. Peters, R. L.; Silverstein, S. D.; Lapp, M.; White, D. R.

1973-01-01

Enhanced scattering and fluorescence processes in the visible and UV were investigated which will enable improved remote measurements of gas properties. The theoretical relationship between scattering and fluorescence from an isolated molecule in the approach to resonance is examined through analysis of the time dependence of re-emitted light following excitation of pulsed incident light. Quantitative estimates are developed for the relative and absolute intensities of fluorescence and resonance scattering. New results are obtained for depolarization of scattering excited by light at wavelengths within a dissociative continuum. The experimental work was performed in two separate facilities. One of these utilizes argon and krypton lasers, single moded by a tilted etalon, and a 3/4 meter double monochromator. This facility was used to determine properties of the re-emission from NO2, I2 and O3 excited by visible light. The second facility involves a narrow-line dye laser, and a 3/4 meter single monochromator. The dye laser produces pulsed light with 5 nsec pulse duration and 0.005 nm spectral width.

Zn2+ reduction induces neuronal death with changes in voltage-gated potassium and sodium channel currents.

PubMed

Tian, Kun; He, Cong-Cong; Xu, Hui-Nan; Wang, Yu-Xiang; Wang, Hong-Gang; An, Di; Heng, Bin; Pang, Wei; Jiang, Yu-Gang; Liu, Yan-Qiang

2017-05-01

In the present study, cultured rat primary neurons were exposed to a medium containing N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN), a specific cell membrane-permeant Zn 2+ chelator, to establish a model of free Zn 2+ deficiency in neurons. The effects of TPEN-mediated free Zn 2+ ion reduction on neuronal viability and on the performance of voltage-gated sodium channels (VGSCs) and potassium channels (Kvs) were assessed. Free Zn 2+ deficiency 1) markedly reduced the neuronal survival rate, 2) reduced the peak amplitude of I Na , 3) shifted the I Na activation curve towards depolarization, 4) modulated the sensitivity of sodium channel voltage-dependent inactivation to a depolarization voltage, and 5) increased the time course of recovery from sodium channel inactivation. In addition, free Zn 2+ deficiency by TPEN notably enhanced the peak amplitude of transient outward K + currents (I A ) and delayed rectifier K + currents (I K ), as well as caused hyperpolarization and depolarization directional shifts in their steady-state activation curves, respectively. Zn 2+ supplementation reversed the effects induced by TPEN. Our results indicate that free Zn 2+ deficiency causes neuronal damage and alters the dynamic characteristics of VGSC and Kv currents. Thus, neuronal injury caused by free Zn 2+ deficiency may correlate with its modulation of the electrophysiological properties of VGSCs and Kvs. Copyright © 2017 Elsevier GmbH. All rights reserved.

Electrical properties associated with wide intercellular clefts in rabbit Purkinje fibres.

PubMed Central

Colatsky, T J; Tsien, R W

1979-01-01

1. Rabbit Purkinje fibres were studied using micro-electrode recordings of electrical activity or a two-micro-electrode voltage clamp. Previous morphological work had suggested that these preparations offer structural advantages for the analysis of ionic permeability mechanisms. 2. Viable preparations could be obtained consistently by exposure to a K glutamate Tyrode solution during excision and recovery. In NaCl Tyrode solution, the action potential showed a large overshoot and fully developed plateau, but no pacemaker depolarization at negative potentials. 3. The passive electrical properties were consistent with morphological evidence for the accessibility of cleft membranes within the cell bundle. Electrotonic responses to intracellular current steps showed the behaviour expected for a simple leaky capacitative cable. Capacitative current transients under voltage clamp were changed very little by an eightfold reduction in the external solution conductivity. 4. Slow current changes attributable to K depletion were small compared to those found in other cardiac preparations. The amount of depletion was close to that predicted by a cleft model which assumed free K diffusion in 1 micron clefts. 5. Step depolarizations over the plateau range of potentials evoked a slow inward current which was resistant to tetrodotoxin but blocked by D600. 6. Strong depolarizations to potentials near 0 mV elicited a transient outward current and a slowly activating late outward current. Both components resembled currents found in sheep or calf Purkinje fibres. 7. These experiments support previous interpretations of slow plateau currents in terms of genuine permeability changes. The rabbit Purkinje fibre may allow various ionic channels to be studied with relatively little interference from radial non-uniformities in membrane potential or ion concentration. Images Fig. 7 PMID:469754

Microglial K+ Channel Expression in Young Adult and Aged Mice

PubMed Central

Schilling, Tom; Eder, Claudia

2015-01-01

The K+ channel expression pattern of microglia strongly depends on the cells' microenvironment and has been recognized as a sensitive marker of the cells' functional state. While numerous studies have been performed on microglia in vitro, our knowledge about microglial K+ channels and their regulation in vivo is limited. Here, we have investigated K+ currents of microglia in striatum, neocortex and entorhinal cortex of young adult and aged mice. Although almost all microglial cells exhibited inward rectifier K+ currents upon membrane hyperpolarization, their mean current density was significantly enhanced in aged mice compared with that determined in young adult mice. Some microglial cells additionally exhibited outward rectifier K+ currents in response to depolarizing voltage pulses. In aged mice, microglial outward rectifier K+ current density was significantly larger than in young adult mice due to the increased number of aged microglial cells expressing these channels. Aged dystrophic microglia exhibited outward rectifier K+ currents more frequently than aged ramified microglia. The majority of microglial cells expressed functional BK-type, but not IK- or SK-type, Ca2+-activated K+ channels, while no differences were found in their expression levels between microglia of young adult and aged mice. Neither microglial K+ channel pattern nor K+ channel expression levels differed markedly between the three brain regions investigated. It is concluded that age-related changes in microglial phenotype are accompanied by changes in the expression of microglial voltage-activated, but not Ca2+-activated, K+ channels. PMID:25472417

The origin of the post-tetanic hyperpolarization of mammalian motor nerve terminals

PubMed Central

Gage, P. W.; Hubbard, J. I.

1966-01-01

1. Motor nerve terminals in magnesium-poisoned rat hemidiaphragm-phrenic nerve preparations in vitro were stimulated with short depolarizing pulses of approximately threshold strength and the evoked antidromic responses recorded from the phrenic nerve. The percentage of these 1/sec or 0·5/sec stimuli to which there was no antidromic response was used as a quantitative measure of the terminal excitability. After standard tetanic stimulation (1000 impulses at 100/sec) the excitability of the terminals was depressed for an average duration of 60-70 sec, during most of which time no antidromic responses to stimuli of pretetanic intensity were recorded. There was no significant interaction between stimuli to the terminals at rates of 1 or 0·5/sec. 2. Potassium-free solutions at first increased, then decreased, the post-tetanic depression of excitability. Raising [K]o threefold (15 mM) abolished the post-tetanic depression and often converted it to an exaltation of excitability. 3. Polarizing currents were applied to the terminals with a second electrode. Depolarizing currents increased, while hyperpolarizing currents decreased, the post-tetanic depression of excitability. 4. In solutions with 70% of the normal NaCl content replaced by sucrose, the post-tetanic depression of excitability was reversibly prolonged. 5. In the presence of 7·7 × 10-6 M digoxin or 0·42 mM ouabain there was a small reversible reduction of post-tetanic excitability. 6. After exposure to solutions containing no glucose or to solutions containing 3-5 mM sodium azide the excitability of the terminals was not altered by the tetanus. After washing with the control solution, post-tetanic depression of excitability returned. Antimycin-A (1·8 × 10-6 M) had little or no effect upon post-tetanic excitability. 7. It was concluded that the post-tetanic depression of excitability reflected hyperpolarization of the terminals and that this hyperpolarization was caused by a shift of the membrane potential towards the potassium equilibrium potential because of an increase in potassium permeability. ImagesFig. 1 PMID:5921834

Contribution of Ih to the relative facilitation of synaptic responses induced by carbachol in the entorhinal cortex during repetitive stimulation of the parasubiculum.

PubMed

Sparks, D W; Chapman, C A

2014-10-10

Neurons in the superficial layers of the entorhinal cortex provide the hippocampus with the majority of its cortical sensory input, and also receive the major output projection from the parasubiculum. This puts the parasubiculum in a position to modulate the activity of entorhinal neurons that project to the hippocampus. These brain areas receive cholinergic projections that are active during periods of theta- and gamma-frequency electroencephalographic (EEG) activity. The purpose of this study was to investigate how cholinergic receptor activation affects the strength of repetitive synaptic responses at these frequencies in the parasubiculo-entorhinal pathway and the cellular mechanisms involved. Whole-cell patch-clamp recordings of rat layer II medial entorhinal neurons were conducted using an acute slice preparation, and responses to 5-pulse trains of stimulation at theta- and gamma-frequency delivered to the parasubiculum were recorded. The cholinergic agonist carbachol (CCh) suppressed the amplitude of single synaptic responses, but also produced a relative facilitation of synaptic responses evoked during stimulation trains. The N-methyl-d-aspartate (NMDA) glutamate receptor blocker APV did not significantly reduce the relative facilitation effect. However, the hyperpolarization-activated cationic current (Ih) channel blocker ZD7288 mimicked the relative facilitation induced by CCh, suggesting that CCh-induced inhibition of Ih could produce the effect by increasing dendritic input resistance (Rin). Inward-rectifying and leak K(+) currents are known to interact with Ih to affect synaptic excitability. Application of the K(+) channel antagonist Ba(2+) depolarized neurons and enhanced temporal summation, but did not block further facilitation of train-evoked responses by ZD7288. The Ih-dependent facilitation of synaptic responses can therefore occur during reductions in inward-rectifying potassium current (IKir) associated with dendritic depolarization. Thus, in addition to cholinergic reductions in transmitter release that are known to facilitate train-evoked responses, these findings emphasize the role of inhibition of Ih in the integration of synaptic inputs within the entorhinal cortex during cholinergically-induced oscillatory states, likely due to enhanced summation of excitatory postsynaptic potentials (EPSPs) induced by increases in dendritic Rin. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

A method for recording resistance changes non-invasively during neuronal depolarization with a view to imaging brain activity with electrical impedance tomography.

PubMed

Gilad, Ori; Ghosh, Anthony; Oh, Dongin; Holder, David S

2009-05-30

Electrical impedance tomography (EIT) is a recently developed medical imaging method which has the potential to produce images of fast neuronal depolarization in the brain. The principle is that current remains in the extracellular space at rest but passes into the intracellular space during depolarization through open ion channels. As current passes into the intracellular space across the capacitance of cell membranes at higher frequencies, applied current needs to be below 100 Hz. A method is presented for its measurement with subtraction of the contemporaneous evoked potentials which occur in the same frequency band. Neuronal activity is evoked by stimulation and resistance is recorded from the potentials resulting from injection of a constant current square wave at 1 Hz with amplitude less than 25% of the threshold for stimulating neuronal activity. Potentials due to the evoked activity and the injected square wave are removed by subtraction. The method was validated with compound action potentials in crab walking leg nerve. Resistance changes of -0.85+/-0.4% (mean+/-SD) occurred which decreased from -0.97+/-0.43% to -0.46+/-0.16% with spacing of impedance current application electrodes from 2 to 8 mm but did not vary significantly with applied currents of 1-10 microA. These tallied with biophysical modelling, and so were consistent with a genuine physiological origin. This method appears to provide a reproducible and artefact free means for recording resistance changes during neuronal activity which could lead to the long-term goal of imaging of fast neural activity in the brain.

Effects of cell volume changes on membrane ionic permeabilities and sodium transport in frog skin (Rana ridibunda).

PubMed

Costa, P M; Fernandes, P L; Ferreira, H G; Ferreira, K T; Giraldez, F

1987-12-01

1. Membrane potential and conductances and short-circuit current were continuously measured with microelectrodes and conventional electrophysiological techniques in a stripped preparation of frog skin epithelium. The effects of the removal of chloride or sodium ions and the concentration or dilution of the serosal (inner) bathing solution were studied. 2. Chloride- or sodium-free solutions produced a cell depolarization of about 30 mV in parallel with a fall in the short-circuit current. Mucosal and serosal membrane conductances both decreased and the sodium permeability of the mucosal barrier was calculated to fall to about one-half its value in standard Ringer solution. The observed decrease in the short-circuit current is probably related to the combined effect of the decrease in sodium permeability and the decrease in the driving force across the mucosal membrane. 3. The removal of chloride or sodium ions reduced the depolarization caused by serosal perfusion with high-potassium solutions (50 mM-KCl). The ratio of the change in cell membrane potential under short-circuit conditions to the change in the potassium equilibrium potential (delta Ec(s.c.)/delta EK), was 0.59 in standard Ringer solution and 0.26 and 0.24 after the removal of chloride or sodium respectively. The depolarizing effect of barium-containing solutions (2 mM-BaCl2) was also markedly reduced in chloride- or sodium-free solutions, suggesting a decrease of the potassium selectivity of the serosal membrane in these conditions. 4. Increasing the osmolality of the serosal bathing solution produced similar effects, i.e. cell depolarization, fall in the short-circuit current and membrane conductances and reduction of the depolarizing effect of high-potassium and barium solutions. On the contrary, dilution of the serosal bath produced the opposite effects, consistent with an increase in the serosal permeability to potassium. 5. The effects of chloride- or sodium-free solutions were reversed by the dilution of the serosal bath. Cells repolarized when exposed to low-osmolality solutions after being in the absence of serosal chloride or sodium. The repolarization ran in parallel with the restoration of the short-circuit current and the potassium selectivity of the serosal membrane. 6. The results show that the effects produced by the removal of sodium or chloride ions from the serosal bathing solution are most probably mediated by a reduction in cell volume. Cell volume changes would lead to changes in the serosal membrane selectivity to potassium and thus to changes in cell membrane potential and sodium transport.(ABSTRACT TRUNCATED AT 400 WORDS)

Depolarization of the conductance-voltage relationship in the NaV1.5 mutant, E1784K, is due to altered fast inactivation

PubMed Central

Yu, Alec; Zhu, Wandi; Silva, Jonathan R.; Ruben, Peter C.

2017-01-01

E1784K is the most common mixed long QT syndrome/Brugada syndrome mutant in the cardiac voltage-gated sodium channel NaV1.5. E1784K shifts the midpoint of the channel conductance-voltage relationship to more depolarized membrane potentials and accelerates the rate of channel fast inactivation. The depolarizing shift in the midpoint of the conductance curve in E1784K is exacerbated by low extracellular pH. We tested whether the E1784K mutant shifts the channel conductance curve to more depolarized membrane potentials by affecting the channel voltage-sensors. We measured ionic currents and gating currents at pH 7.4 and pH 6.0 in Xenopus laevis oocytes. Contrary to our expectation, the movement of gating charges is shifted to more hyperpolarized membrane potentials by E1784K. Voltage-clamp fluorimetry experiments show that this gating charge shift is due to the movement of the DIVS4 voltage-sensor being shifted to more hyperpolarized membrane potentials. Using a model and experiments on fast inactivation-deficient channels, we show that changes to the rate and voltage-dependence of fast inactivation are sufficient to shift the conductance curve in E1784K. Our results localize the effects of E1784K to DIVS4, and provide novel insight into the role of the DIV-VSD in regulating the voltage-dependencies of activation and fast inactivation. PMID:28898267

Depolarization of the conductance-voltage relationship in the NaV1.5 mutant, E1784K, is due to altered fast inactivation.

PubMed

Peters, Colin H; Yu, Alec; Zhu, Wandi; Silva, Jonathan R; Ruben, Peter C

2017-01-01

E1784K is the most common mixed long QT syndrome/Brugada syndrome mutant in the cardiac voltage-gated sodium channel NaV1.5. E1784K shifts the midpoint of the channel conductance-voltage relationship to more depolarized membrane potentials and accelerates the rate of channel fast inactivation. The depolarizing shift in the midpoint of the conductance curve in E1784K is exacerbated by low extracellular pH. We tested whether the E1784K mutant shifts the channel conductance curve to more depolarized membrane potentials by affecting the channel voltage-sensors. We measured ionic currents and gating currents at pH 7.4 and pH 6.0 in Xenopus laevis oocytes. Contrary to our expectation, the movement of gating charges is shifted to more hyperpolarized membrane potentials by E1784K. Voltage-clamp fluorimetry experiments show that this gating charge shift is due to the movement of the DIVS4 voltage-sensor being shifted to more hyperpolarized membrane potentials. Using a model and experiments on fast inactivation-deficient channels, we show that changes to the rate and voltage-dependence of fast inactivation are sufficient to shift the conductance curve in E1784K. Our results localize the effects of E1784K to DIVS4, and provide novel insight into the role of the DIV-VSD in regulating the voltage-dependencies of activation and fast inactivation.

Ionic mechanisms of transient inward current in the absence of Na(+)-Ca2+ exchange in rabbit cardiac Purkinje fibres.

PubMed Central

Han, X; Ferrier, G R

1992-01-01

1. Membrane currents were measured with a two-microelectrode technique in voltage clamped rabbit cardiac Purkinje fibres under conditions known to cause intracellular calcium overload and to eliminate or minimize Na(+)-Ca2+ exchange. 2. Increasing [Ca2+]o from 2.5 to 5 mM or above and substituting external sodium with either sucrose, choline or Li+ induced an oscillatory transient inward current (TI) which peaked 200-300 ms after repolarization from a previous depolarizing pulse. The TI quickly disappeared upon return to normal Tyrode solution. Both the rate and configuration of action potentials of Purkinje fibres also returned to control upon return to Tyrode solution after 30 min of high Ca2+ exposure, if the Ca2+ concentration was 30 mM or less. 3. The TI in Na(+)-free solution was Ca2+ dependent. Either zero or low (2.5 mM) [Ca2+]o, or replacement of [Ca2+]o by BaCl prevented induction of the TI current upon repolarization from a previous depolarizing pulse. 4. In the presence of 30 mM-CaCl2 and with choline chloride as the substitute for NaCl, TI had a distinct reversal potential (Erev) of -25 mV. The time-to-peak TI, either inward or outward, did not shift significantly with change in voltage. Both inward and outward TI were simultaneously abolished by exposure to 1 microM-ryanodine, suggesting they were both activated by transient release of Ca2+ from the sarcoplasmic reticulum. The occurrence of TI in the absence of [Na+]o is not compatible with an electrogenic Na(+)-Ca2+ exchange mechanism. The existence of a clear-cut reversal potential suggests that an ionic channel may be responsible for the TI under these conditions. 5. Both the magnitude of peak TI and the Erev were affected by changes of CaCl2 concentration. (i) Under steady-state conditions, peak inward TI was significantly increased when the [Ca2+]o was elevated from 5 to 15 mM. The peak TI in the outward direction was significantly increased when [Ca2+]o was elevated from 15 to 30 mM; however, the difference in peak inward TI at 15 and 30 mM [Ca2+]o was small. (ii) Clear-cut reversals of TI were found at Ca2+ concentrations of 10 mM (Erev = -19.5 mV) or greater, and elevation of [Ca2+]o to 20, 30, 50 and 105 mM shifted the Erev to more negative potentials. (iii) In the presence of 5 mM [Ca2+]o the inward TI declined to zero at about -30 mV, and test voltages between -55 and +5 mV failed to reveal a distinct outward TI.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:1284077

Target reflectance measurements for calibration of lidar atmospheric backscatter data

NASA Technical Reports Server (NTRS)

Kavaya, M. J.; Menzies, R. T.; Haner, D. A.; Oppenheim, U. P.; Flamant, P. H.

1983-01-01

Wavelength and angular dependence of reflectances and depolarization in the 9-11 micron region are reported for four standard targets: flowers of sulfur, flame-sprayed aluminum, 20-grit sandblasted aluminum, and 400-grit silicon carbon sandpaper. Measurements are presented and compared using a CW CO2 grating-tunable laser in a laboratory backscatter apparatus, an integrating sphere, and a coherent pulsed TEA-CO2 lidar system operating in the 9-11 micron region. Reflectance theory related to the use of hard targets to calibrate lidar atmospheric backscatter data is discussed.

Effect of glutamate, aspartate and related derivatives on cerebellar Purkinje cell dendrites in the rat: an in vitro study

PubMed Central

Crepel, F.; Dhanjal, S. S.; Sears, T. A.

1982-01-01

1. The responses of Purkinje cells to short duration (pulse) ionophoretic applications of L-aspartate (L-asp), L-glutamate (L-glu), N-methyl DL-aspartate (NMDLA) and quisqualic acid in their dendritic fields were studied in vitro on sagittal slices of lobules IX and X of the adult rat cerebellum. 2. Pulse application of L-asp or L-glu evoked transient and dose-dependent increases in the firing rate of the simple spikes recorded extracellularly as single units. When the ionophoretic electrode was positioned in the dendritic field of the Purkinje cells, the lowest thresholds for L-glu and L-asp mediated excitations of the cells were as low as 25 and 35 pC respectively, with a latency for maximal responses as brief as 7 ms. 3. In intracellular recordings these excitatory responses consisted of depolarizations of up to 18 mV in amplitude and with depolarizing slopes up to 0·52 mV/ms. They were generally unaccompanied by changes in cell input resistance in contrast to the marked decrease which occurred in response to steady applications of large doses of L-asp and L-glu. 4. The spatial distribution of the excitatory sites confirmed that the dendritic sensitivity to L-glu was greater than that of the soma and showed that the same was true for L-asp. In 34% of cells the sensitivity for L-asp declined markedly in the upper region of the molecular layer, whereas it remained high for L-glu; no such differential sensitivity was detected in the remaining 66% of cells. 5. Inhibitory responses, antagonized by 10-5 M-bicuculline in the bath, were also induced in Purkinje cells by L-glu and L-asp when the ionophoretic electrode was withdrawn from the excitatory sites by as little as 8 μm and up to 40 μm upward or downward along the track of parallel fibres or positioned as far as 250 μm laterally. 6. Whenever it was applied in the molecular layer, the pulse application of NMDLA elicited no excitatory response in Purkinje cells recorded extra or intracellularly. However, slow depolarizations accompanied by a slight increase in cell input resistance were obtained with steady applications of 20-50 nA of the drug for 20-30 s. 7. In contrast, pulse application of quisqualic acid appeared to have the same type of fast excitatory effect on Purkinje cells as L-asp and L-glu, but its potency was greater and its action more prolonged. Furthermore, its steady application led to an abrupt and marked decrease in cell membrane resistance. 8. The excitatory effects of L-asp, L-glu and quisqualic acid were antagonized by L-glutamic acid diethyl ester more consistently than by D-α-aminoadipate, suggesting together with previous observations that L-asp and L-glu act on Purkinje cells via quisqualic acid rather than via NMDLA receptors. PMID:6754909

[Patterns of action potential firing in cortical neurons of neonatal mice and their electrophysiological property].

PubMed

Furong, Liu; Shengtian, L I

2016-05-25

To investigate patterns of action potential firing in cortical heurons of neonatal mice and their electrophysiological properties. The passive and active membrane properties of cortical neurons from 3-d neonatal mice were observed by whole-cell patch clamp with different voltage and current mode. Three patterns of action potential firing were identified in response to depolarized current injection. The effects of action potential firing patterns on voltage-dependent inward and outward current were found. Neurons with three different firing patterns had different thresholds of depolarized current. In the morphology analysis of action potential, the three type neurons were different in rise time, duration, amplitude and threshold of the first action potential evoked by 80 pA current injection. The passive properties were similar in three patterns of action potential firing. These results indicate that newborn cortical neurons exhibit different patterns of action potential firing with different action potential parameters such as shape and threshold.

Sweet taste transduction in hamster: sweeteners and cyclic nucleotides depolarize taste cells by reducing a K+ current.

PubMed

Cummings, T A; Daniels, C; Kinnamon, S C

1996-03-01

1. The gigaseal voltage-clamp technique was used to record responses of hamster taste receptor cells to synthetic sweeteners and cyclic nucleotides. Voltage-dependent currents and steady-state currents were monitored during bath exchanges of saccharin, two high-potency sweeteners, 8-chlorophenylthio-adenosine 3',5'-cyclic monophosphate (8cpt-cAMP), and dibutyryl-guanosine 3',5'-cyclic monophosphate (db-cGMP). 2. Of the 237 fungiform taste cells studied, only one in eight was sweet responsive. Outward currents, both voltage-dependent and resting, were reduced by all of the sweeteners tested in sweet-responsive taste cells, whereas these currents were unaffected by sweeteners in sweet-unresponsive taste cells. 3. In every sweet-responsive cell tested, 8cpt-cAMP and db-cGMP mimicked the response to the sweeteners, but neither nucleotide elicited responses in sweet-unresponsive cells. Thus there was a one-to-one correlation between sweet responsivity and cyclic nucleotide responsivity. 4. Sweet responses showed cross adaptation with cyclic nucleotide responses. This indicates that the same ion channel is modulated by sweeteners and cyclic nucleotides. 5. The sweetener- and cyclic nucleotide-blocked current had an apparent reversal potential of -50 mV, which was close to the potassium reversal potential in these experiments. In addition, there was no effect of sweeteners and cyclic nucleotides in the presence of the K+ channel blocker tetraethylammonium bromide (TEA). These data suggest that block of a resting, TEA-sensitive K+ current is the final common step leading to taste cell depolarization during sweet transduction. 6. These data, together with data from a previous study (Cummings et al. 1993), suggest that both synthetic sweeteners and sucrose utilize second-messenger pathways that block a resting K+ conductance to depolarize the taste cell membrane.

Vertical separation of the atmospheric aerosol components by using poliphon retrieval in polarized micro pulse lidar (P-MPL) measurements: case studies of specific climate-relevant aerosol types

NASA Astrophysics Data System (ADS)

Córdoba-Jabonero, Carmen; Sicard, Michaël; Ansmann, Albert; Águila, Ana del; Baars, Holger

2018-04-01

POLIPHON (POlarization-LIdar PHOtometer Networking) retrieval consists in the vertical separation of two/three particle components in aerosol mixtures, highlighting their relative contributions in terms of the optical properties and mass concentrations. This method is based on the specific particle linear depolarization ratio given for different types of aerosols, and is applied to the new polarized Micro-Pulse Lidar (P-MPL). Case studies of specific climate-relevant aerosols (dust particles, fire smoke, and pollen aerosols, including a clean case as reference) observed over Barcelona (Spain) are presented in order to evaluate firstly the potential of P-MPLs measurements in combination with POLIPHON for retrieving the vertical separation of those particle components forming aerosol mixtures and their properties.

pH modulation of glial glutamate transporters regulates synaptic transmission in the nucleus of the solitary tract

PubMed Central

McCrimmon, Donald R.; Martina, Marco

2013-01-01

The nucleus of the solitary tract (NTS) is the major site for termination of visceral sensory afferents contributing to homeostatic regulation of, for example, arterial pressure, gastric motility, and breathing. Whereas much is known about how different neuronal populations influence these functions, information about the role of glia remains scant. In this article, we propose that glia may contribute to NTS functions by modulating excitatory neurotransmission. We found that acidification (pH 7.0) depolarizes NTS glia by inhibiting K+-selective membrane currents. NTS glia also showed functional expression of voltage-sensitive glutamate transporters, suggesting that extracellular acidification regulates synaptic transmission by compromising glial glutamate uptake. To test this hypothesis, we evoked glutamatergic slow excitatory potentials (SEPs) in NTS neurons with repetitive stimulation (20 pulses at 10 Hz) of the solitary tract. This SEP depends on accumulation of glutamate following repetitive stimulation, since it was potentiated by blocking glutamate uptake with dl-threo-β-benzyloxyaspartic acid (TBOA) or a glia-specific glutamate transport blocker, dihydrokainate (DHK). Importantly, extracellular acidification (pH 7.0) also potentiated the SEP. This effect appeared to be mediated through a depolarization-induced inhibition of glial transporter activity, because it was occluded by TBOA and DHK. In agreement, pH 7.0 did not directly alter d-aspartate-induced responses in NTS glia or properties of presynaptic glutamate release. Thus acidification-dependent regulation of glial function affects synaptic transmission within the NTS. These results suggest that glia play a modulatory role in the NTS by integrating local tissue signals (such as pH) with synaptic inputs from peripheral afferents. PMID:23615553

Reactive oxygen species alters the electrophysiological properties and raises [Ca2+]i in intracardiac ganglion neurons

PubMed Central

Dyavanapalli, Jhansi; Rimmer, Katrina

2010-01-01

We have investigated the effects of the reactive oxygen species (ROS) donors hydrogen peroxide (H2O2) and tert-butyl hydroperoxide (t-BHP) on the intrinsic electrophysiological characteristics: ganglionic transmission and resting [Ca2+]i in neonate and adult rat intracardiac ganglion (ICG) neurons. Intracellular recordings were made using sharp microelectrodes filled with either 0.5 M KCl or Oregon Green 488 BAPTA-1, allowing recording of electrical properties and measurement of [Ca2+]i. H2O2 and t-BHP both hyperpolarized the resting membrane potential and reduced membrane resistance. In adult ICG neurons, the hyperpolarizing action of H2O2 was reversed fully by Ba2+ and partially by tetraethylammonium, muscarine, and linopirdine. H2O2 and t-BHP reduced the action potential afterhyperpolarization (AHP) amplitude but had no impact on either overshoot or AHP duration. ROS donors evoked an increase in discharge adaptation to long depolarizing current pulses. H2O2 blocked ganglionic transmission in most ICG neurons but did not alter nicotine-evoked depolarizations. By contrast, t-BHP had no significant action on ganglionic transmission. H2O2 and t-BHP increased resting intracellular Ca2+ levels to 1.6 ( ± 0.6, n = 11, P < 0.01) and 1.6 ( ± 0.3, n = 8, P < 0.001), respectively, of control value (1.0, ∼60 nM). The ROS scavenger catalase prevented the actions of H2O2, and this protection extended beyond the period of application. Superoxide dismutase partially shielded against the action of H2O2, but this was limited to the period of application. These data demonstrate that ROS decreases the excitability and ganglionic transmission of ICG neurons, attenuating parasympathetic control of the heart. PMID:20445155

Diffusion of extracellular K+ can synchronize bursting oscillations in a model islet of Langerhans.

PubMed Central

Stokes, C L; Rinzel, J

1993-01-01

Electrical bursting oscillations of mammalian pancreatic beta-cells are synchronous among cells within an islet. While electrical coupling among cells via gap junctions has been demonstrated, its extent and topology are unclear. The beta-cells also share an extracellular compartment in which oscillations of K+ concentration have been measured (Perez-Armendariz and Atwater, 1985). These oscillations (1-2 mM) are synchronous with the burst pattern, and apparently are caused by the oscillating voltage-dependent membrane currents: Extracellular K+ concentration (Ke) rises during the depolarized active (spiking) phase and falls during the hyperpolarized silent phase. Because raising Ke depolarizes the cell membrane by increasing the potassium reversal potential (VK), any cell in the active phase should recruit nonspiking cells into the active phase. The opposite is predicted for the silent phase. This positive feedback system might couple the cells' electrical activity and synchronize bursting. We have explored this possibility using a theoretical model for bursting of beta-cells (Sherman et al., 1988) and K+ diffusion in the extracellular space of an islet. Computer simulations demonstrate that the bursts synchronize very quickly (within one burst) without gap junctional coupling among the cells. The shape and amplitude of computed Ke oscillations resemble those seen in experiments for certain parameter ranges. The model cells synchronize with exterior cells leading, though incorporating heterogeneous cell properties can allow interior cells to lead. The model islet can also be forced to oscillate at both faster and slower frequencies using periodic pulses of higher K+ in the medium surrounding the islet. Phase plane analysis was used to understand the synchronization mechanism. The results of our model suggest that diffusion of extracellular K+ may contribute to coupling and synchronization of electrical oscillations in beta-cells within an islet. Images FIGURE 1 PMID:8218890

Noradrenaline decreases spike voltage threshold and induces electrographic sharp waves in turtle medial cortex in vitro.

PubMed

Lorenzo, Daniel; Velluti, Julio C

2004-01-01

The noradrenergic modulation of neuronal properties has been described at different levels of the mammalian brain. Although the anatomical characteristics of the noradrenergic system are well known in reptiles, functional data are scarce. In our study the noradrenergic modulation of cortical electrogenesis in the turtle medial cortex was studied in vitro using a combination of field and intracellular recordings. Turtle EEG consists of a low voltage background interspersed by spontaneous large sharp waves (LSWs). Noradrenaline (NA, 5-40 microM) induced (or enhanced) the generation of LSWs in a dose-dependent manner. Pharmacological experiments suggest the participation of alpha and beta receptors in this effect. In medial cortex neurons NA induced a hyperpolarization of the resting potential and a decrease of input resistance. Both effects were observed also after TTX treatment. Noradrenaline increased the response of the cells to depolarizing pulses, resulting in an upward shift of the frequency/current relation. In most cells the excitability change was mediated by a decrease of the spike voltage threshold resulting in the reduction of the amount of depolarization needed to fire the cell (voltage threshold minus resting potential). As opposed to the mechanisms reported in mammalian neurons, no changes in the frequency adaptation or the post-train afterhyperpolarization were observed. The NA effects at the cellular level were not reproduced by noradrenergic agonists. Age- and species-dependent properties in the pharmacology of adrenergic receptors could be involved in this result. Cellular effects of NA in turtle cortex are similar to those described in mammals, although the increase in cellular excitability seems to be mediated by a different mechanism. Copyright 2004 S. Karger AG, Basel

Hydrogen sulphide facilitates exocytosis by regulating the handling of intracellular calcium by chromaffin cells.

PubMed

de Pascual, Ricardo; Baraibar, Andrés M; Méndez-López, Iago; Pérez-Ciria, Martín; Polo-Vaquero, Ignacio; Gandía, Luis; Ohia, Sunny E; García, Antonio G; de Diego, Antonio M G

2018-05-02

Gasotransmitter hydrogen sulphide (H 2 S) has emerged as a regulator of multiple physiological and pathophysiological processes throughout. Here, we have investigated the effects of NaHS (fast donor of H 2 S) and GYY4137 (GYY, slow donor of H 2 S) on the exocytotic release of catecholamines from fast-perifused bovine adrenal chromaffin cells (BCCs) challenged with sequential intermittent pulses of a K + -depolarizing solution. Both donors caused a concentration-dependent facilitation of secretion. This was not due to an augmentation of Ca 2+ entry through voltage-activated Ca 2+ channels (VACCs) because, in fact, NaHS and GYY caused a mild inhibition of whole-cell Ca 2+ currents. Rather, the facilitation of exocytosis seemed to be associated to an augmented basal [Ca 2+ ] c and the K + -elicited [Ca 2+ ] c transients; such effects of H 2 S donors are aborted by cyclopiazonic acid (CPA), that causes endoplasmic reticulum (ER) Ca 2+ depletion through sarcoendoplasmic reticulum Ca2+ ATPase inhibition and by protonophore carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP), that impedes the ability of mitochondria to sequester cytosolic Ca 2+ during cell depolarization. Inasmuch as CPA and FCCP reversed the facilitation of secretion triggered by K + in the presence of NaHS and GYY, is seems that such facilitation is tightly coupled to Ca 2+ handling by the ER and mitochondria. On the basis of these results, we propose that H 2 S regulates catecholamine secretory responses triggered by K + in BCCs by (i) mobilisation of ER Ca 2+ and (ii) interference with mitochondrial Ca 2+ circulation. In so doing, the clearance of the [Ca 2+ ] c transient will be delayed and the Ca 2+ -dependent trafficking of secretory vesicles will be enhanced to overfill the secretory machinery with new vesicles to enhance exocytosis.

Ultrashort Phenomena in Biochemistry and Biological Signaling

NASA Astrophysics Data System (ADS)

Splinter, Robert

2014-11-01

In biological phenomena there are indications that within the long pulse-length of the action potential on millisecond scale, there is additional ultrashort perturbation encoding that provides the brain with detailed information about the origin (location) and physiological characteristics. The objective is to identify the mechanism-of-action providing the potential for encoding in biological signal propagation. The actual molecular processes involved in the initiation of the action potential have been identified to be in the femtosecond and pico-second scale. The depolarization process of the cellular membrane itself, leading to the onset of the actionpotential that is transmitted to the brain, however is in the millisecond timeframe. One example of the femtosecond chemical interaction is the photoresponse of bacteriorhodopsin. No clear indication for the spatial encoding has so far been verified. Further research will be required on a cellular signal analysis level to confirm or deny the spatial and physiological encoding in the signal wave-trains of intercellular communications and sensory stimuli. The pathological encoding process for cardiac depolarization is however very pronounced and validated, however this electro-chemical process is in the millisecond amplitude and frequency modulation spectrum.

Short- and medium-term plasticity associated with augmenting responses in cortical slabs and spindles in intact cortex of cats in vivo

PubMed Central

Timofeev, Igor; Grenier, François; Bazhenov, Maxim; Houweling, Arthur R; Sejnowski, Terrence J; Steriade, Mircea

2002-01-01

Plastic changes in the synaptic responsiveness of neocortical neurones, which occur after rhythmic stimuli within the frequency range of sleep spindles (10 Hz), were investigated in isolated neocortical slabs and intact cortex of anaesthetized cats by means of single, dual and triple simultaneous intracellular recordings in conjunction with recordings of local field potential responses. In isolated cortical slabs (10 mm long, 6 mm wide and 4–5 mm deep), augmenting responses to pulse-trains at 10 Hz (responses with growing amplitudes from the second stimulus in a train) were elicited only by relatively high-intensity stimuli. At low intensities, responses were decremental. The largest augmenting responses were evoked in neurones located close to the stimulation site. Quantitative analyses of the number of action potentials and the amplitude and area of depolarization during augmenting responses in a population of neurones recorded from slabs showed that the most dramatic increases in the number of spikes with successive stimuli, and the greatest increase in depolarization amplitude, were found in conventional fast-spiking (FS) neurones. The largest increase in the area of depolarization was found in regular-spiking (RS) neurones. Dual intracellular recordings from a pair of FS and RS neurones in the slab revealed more action potentials in the FS neurone during augmenting responses and a significant increase in the depolarization area of the RS neurone that was dependent on the firing of the FS neurone. Self-sustained seizures could occur in the slab after rhythmic stimuli at 10 Hz. In the intact cortex, repeated sequences of stimuli generating augmenting responses or spontaneous spindles could induce an increased synaptic responsiveness to single stimuli, which lasted for several minutes. A similar time course of increased responsiveness was obtained with induction of cellular plasticity. These data suggest that augmenting responses elicited by stimulation, as well as spontaneously occurring spindles, may induce short- and medium-term plasticity of neuronal responses. PMID:12122155

Local conductance: A means to extract polarization and depolarizing fields near domain walls in ferroelectrics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Douglas, A. M.; Kumar, A.; Gregg, J. M.

Conducting atomic force microscopy images of bulk semiconducting BaTiO{sub 3} surfaces show clear stripe domain contrast. High local conductance correlates with strong out-of-plane polarization (mapped independently using piezoresponse force microscopy), and current-voltage characteristics are consistent with dipole-induced alterations in Schottky barriers at the metallic tip-ferroelectric interface. Indeed, analyzing current-voltage data in terms of established Schottky barrier models allows relative variations in the surface polarization, and hence the local domain structure, to be determined. Fitting also reveals the signature of surface-related depolarizing fields concentrated near domain walls. Domain information obtained from mapping local conductance appears to be more surface-sensitive than thatmore » from piezoresponse force microscopy. In the right materials systems, local current mapping could therefore represent a useful complementary technique for evaluating polarization and local electric fields with nanoscale resolution.« less

Lidocaine reduces the transition to slow inactivation in Nav1.7 voltage-gated sodium channels

PubMed Central

Sheets, Patrick L; Jarecki, Brian W; Cummins, Theodore R

2011-01-01

BACKGROUND AND PURPOSE The primary use of local anaesthetics is to prevent or relieve pain by reversibly preventing action potential propagation through the inhibition of voltage-gated sodium channels. The tetrodotoxin-sensitive voltage-gated sodium channel subtype Nav1.7, abundantly expressed in pain-sensing neurons, plays a crucial role in perception and transmission of painful stimuli and in inherited chronic pain syndromes. Understanding the interaction of lidocaine with Nav1.7 channels could provide valuable insight into the drug's action in alleviating pain in distinct patient populations. The aim of this study was to determine how lidocaine interacts with multiple inactivated conformations of Nav1.7 channels. EXPERIMENTAL APPROACH We investigated the interactions of lidocaine with wild-type Nav1.7 channels and a paroxysmal extreme pain disorder mutation (I1461T) that destabilizes fast inactivation. Whole cell patch clamp recordings were used to examine the activity of channels expressed in human embryonic kidney 293 cells. KEY RESULTS Depolarizing pulses that increased slow inactivation of Nav1.7 channels also reduced lidocaine inhibition. Lidocaine enhanced recovery of Nav1.7 channels from prolonged depolarizing pulses by decreasing slow inactivation. A paroxysmal extreme pain disorder mutation that destabilizes fast inactivation of Nav1.7 channels decreased lidocaine inhibition. CONCLUSIONS AND IMPLICATIONS Lidocaine decreased the transition of Nav1.7 channels to the slow inactivated state. The fast inactivation gate (domain III–IV linker) is important for potentiating the interaction of lidocaine with the Nav1.7 channel. PMID:21232038

Three types of neuronal calcium channel with different calcium agonist sensitivity.

PubMed

Nowycky, M C; Fox, A P; Tsien, R W

How many types of calcium channels exist in neurones? This question is fundamental to understanding how calcium entry contributes to diverse neuronal functions such as transmitter release, neurite extension, spike initiation and rhythmic firing. There is considerable evidence for the presence of more than one type of Ca conductance in neurones and other cells. However, little is known about single-channel properties of diverse neuronal Ca channels, or their responsiveness to dihydropyridines, compounds widely used as labels in Ca channel purification. Here we report evidence for the coexistence of three types of Ca channel in sensory neurones of the chick dorsal root ganglion. In addition to a large conductance channel that contributes long-lasting current at strong depolarizations (L), and a relatively tiny conductance that underlies a transient current activated at weak depolarizations (T), we find a third type of unitary activity (N) that is neither T nor L. N-type Ca channels require strongly negative potentials for complete removal of inactivation (unlike L) and strong depolarizations for activation (unlike T). The dihydropyridine Ca agonist Bay K 8644 strongly increases the opening probability of L-, but not T- or N-type channels.

Nicotinic excitation of rat ventral tegmental neurones in vitro studied by intracellular recording.

PubMed Central

Calabresi, P.; Lacey, M. G.; North, R. A.

1989-01-01

1. Intracellular recordings were made from presumed dopamine-containing neurones in the ventral tegmental area (VTA) in rat brain slices. 2. Nicotine (10-100 microM) and acetylcholine (ACh) depolarized the neurones. The depolarization caused by ACh was typically biphasic; both components were increased by neostigmine (0.1-10 microM), but only the slower component was blocked by scopolamine (1-10 microM). 3. The nicotinic action of ACh, studied in the presence of neostigmine and scopolamine, persisted in the presence of tetrodotoxin (1 microM) and cobalt (2-5 mM). 4. ACh or carbachol (30 microM) caused inward currents in neurones voltage-clamped near the resting potential. These currents reversed polarity at around -4 mV, were blocked by hexamethonium (1-100 microM) in a voltage-dependent manner, and showed desensitization with prolonged or repeated agonist applications. 5. Depolarizations caused by ACh and carbachol were reduced in slices pretreated with kappa-bungarotoxin, but were not changed by alpha-bungarotoxin. 6. These responses to ACh and nicotine resemble those previously described on autonomic ganglion cells. The direct action on VTA neurones may contribute to the positive reinforcement associated with nicotine consumption. PMID:2804543

Spontaneous and noradrenaline-induced transient depolarizations in the smooth muscle of guinea-pig mesenteric vein.

PubMed

Van Helden, D F

1991-06-01

1. Recordings of membrane current were made in the smooth muscle of short segments of mesenteric vein before or during stimulation with noradrenaline (NA). 2. Small veins (diameter less than 150 microns) when cut into short segments (of length less than 250 microns) had the passive electrical characteristics of short cables both before and during activation with NA. 3. Spontaneous transient depolarizations (STDs) or the underlying inward currents (STICs) were recorded in these preparations. STDs were of myogenic origin as they were not blocked by tetrodotoxin or antagonists to the alpha-adrenoreceptor and persisted after either denervation or disruption of the endothelium. 4. STDs had time courses similar to the underlying currents and were generally slow compared to the membrane time constant of the short segments. 5. STDs and the underlying currents showed large variability in frequency and amplitude both within and between short segments. Currents were typically less than 0.3 nA, were characteristic in shape, had half-durations normally in the range 0.1-0.7 s and reversed at about -25 mV. 6. STDs persisted, but at markedly reduced frequencies, after exposure (3-10 min) to a solution in which cobalt ions had been used to substitute for Ca2+. STDs were also substantially suppressed by exposure to low-chloride solution. 7. Caffeine induced excitatory and inhibitory conductances. An initial component of the caffeine-induced responses showed similar voltage dependence to STDs and was also suppressed by exposure to low-chloride solution. 8. NA, through activation of alpha-adrenoreceptors, caused a sustained depolarization or inward current (under voltage clamp) with considerable membrane potential or current noise often in the form of agonist-induced spontaneous transient depolarizations (ASTDs) or currents (ASTICs). There were marked increases in amplitude and frequency of ASTDs with increase in NA concentrations. 9. ASTDs appeared to be generated within the smooth muscle as they were activated in preparations which had been denervated or in which the endothelium had been disrupted. 10. Except for the pathway of activation, ASTDs were indistinguishable from STDs having half-durations in the same range (0.1-2 s with the majority less than 0.7 s). The underlying currents again showed large variation in amplitude (typically less than 0.3 nA; maximum recorded 0.9 nA). They reversed at about -25 mV, could still be elicited in cobalt solution (but at reduced intensity for long exposures to this low-Ca2+ solution) and were reduced by long term exposure to low-chloride solution.(ABSTRACT TRUNCATED AT 400 WORDS)

Temperature dependent impedance spectroscopy and Thermally Stimulated Depolarization Current (TSDC) analysis of disperse red 1-co-poly(methyl methacrylate) copolymers

NASA Astrophysics Data System (ADS)

Ko, Yee Song; Cuervo-Reyes, Eduardo; Nüesch, Frank A.; Opris, Dorina M.

2016-04-01

The dielectric relaxation processes of polymethyl methacrylates that have been functionalized with Disperse Red 1 (DR1) in the side chain (DR1-co-MMA) were studied with temperature dependent impedance spectroscopy and thermally stimulated depolarization current (TSDC) techniques. Copolymers with dipole contents which varied between 10 mol% and 70 mol% were prepared. All samples showed dipole relaxations above the structural-glass transition temperature (Tg). The β-relaxation of the methyl methacrylate (MMA) repeating unit was most visible in DR1(10%)-co-MMA and rapidly vanishes with higher dipole contents. DSC data reveal an increase of the Tg by 20 °C to 125°C with the inclusion of the dipole into the polymethyl methacrylate (PMMA) as side chain. The impedance data of samples with several DR1 concentrations, taken at several temperatures above Tg, have been fitted with the Havriliak-Negami (HN) function. In all cases, the fits reveal a dielectric response that corresponds to power-law dipolar relaxations. TSDC measurements show that the copolymer can be poled, and that the induced polarization can be frozen by lowering the temperature well below the glass transition. Relaxation strengths ΔƐ estimated by integrating the depolarization current are similar to those obtained from the impedance data, confirming the efficient freezing of the dipoles in the structural glass state.

Seizure-induced alterations in fast-spiking basket cell GABA currents modulate frequency and coherence of gamma oscillation in network simulations

NASA Astrophysics Data System (ADS)

Proddutur, Archana; Yu, Jiandong; Elgammal, Fatima S.; Santhakumar, Vijayalakshmi

2013-12-01

Gamma frequency oscillations have been proposed to contribute to memory formation and retrieval. Fast-spiking basket cells (FS-BCs) are known to underlie development of gamma oscillations. Fast, high amplitude GABA synapses and gap junctions have been suggested to contribute to gamma oscillations in FS-BC networks. Recently, we identified that, apart from GABAergic synapses, FS-BCs in the hippocampal dentate gyrus have GABAergic currents mediated by extrasynaptic receptors. Our experimental studies demonstrated two specific changes in FS-BC GABA currents following experimental seizures [Yu et al., J. Neurophysiol. 109, 1746 (2013)]: increase in the magnitude of extrasynaptic (tonic) GABA currents and a depolarizing shift in GABA reversal potential (EGABA). Here, we use homogeneous networks of a biophysically based model of FS-BCs to examine how the presence of extrasynaptic GABA conductance (gGABA-extra) and experimentally identified, seizure-induced changes in gGABA-extra and EGABA influence network activity. Networks of FS-BCs interconnected by fast GABAergic synapses developed synchronous firing in the dentate gamma frequency range (40-100 Hz). Systematic investigation revealed that the biologically realistic range of 30 to 40 connections between FS-BCs resulted in greater coherence in the gamma frequency range when networks were activated by Poisson-distributed dendritic synaptic inputs rather than by homogeneous somatic current injections, which were balanced for FS-BC firing frequency in unconnected networks. Distance-dependent conduction delay enhanced coherence in networks with 30-40 FS-BC interconnections while inclusion of gap junctional conductance had a modest effect on coherence. In networks activated by somatic current injections resulting in heterogeneous FS-BC firing, increasing gGABA-extra reduced the frequency and coherence of FS-BC firing when EGABA was shunting (-74 mV), but failed to alter average FS-BC frequency when EGABA was depolarizing (-54 mV). When FS-BCs were activated by biologically based dendritic synaptic inputs, enhancing gGABA-extra reduced the frequency and coherence of FS-BC firing when EGABA was shunting and increased average FS-BC firing when EGABA was depolarizing. Shifting EGABA from shunting to depolarizing potentials consistently increased network frequency to and above high gamma frequencies (>80 Hz). Since gamma oscillations may contribute to learning and memory processing [Fell et al., Nat. Neurosci. 4, 1259 (2001); Jutras et al., J. Neurosci. 29, 12521 (2009); Wang, Physiol. Rev. 90, 1195 (2010)], our demonstration that network oscillations are modulated by extrasynaptic inhibition in FS-BCs suggests that neuroactive compounds that act on extrasynaptic GABA receptors could impact memory formation by modulating hippocampal gamma oscillations. The simulation results indicate that the depolarized FS-BC GABA reversal, observed after experimental seizures, together with enhanced spillover extrasynaptic GABA currents are likely to promote generation of focal high frequency activity associated with epileptic networks.

Enhanced diagnostic of skin conditions by polarized laser speckles: phantom studies and computer modeling

NASA Astrophysics Data System (ADS)

Tchvialeva, Lioudmila; Lee, Tim K.; Markhvida, Igor; Zeng, Haishan; Doronin, Alexander; Meglinski, Igor

2014-03-01

The incidence of the skin melanoma, the most commonly fatal form of skin cancer, is increasing faster than any other potentially preventable cancer. Clinical practice is currently hampered by the lack of the ability to rapidly screen the functional and morphological properties of tissues. In our previous study we show that the quantification of scattered laser light polarization provides a useful metrics for diagnostics of the malignant melanoma. In this study we exploit whether the image speckle could improve skin cancer diagnostic in comparison with the previously used free-space speckle. The study includes skin phantom measurements and computer modeling. To characterize the depolarization of light we measure the spatial distribution of speckle patterns and analyse their depolarization ratio taken into account radial symmetry. We examine the dependences of depolarization ratio vs. roughness for phantoms which optical properties are of the order of skin lesions. We demonstrate that the variation in bulk optical properties initiates the assessable changes in the depolarization ratio. We show that image speckle differentiates phantoms significantly better than free-space speckle. The results of experimental measurements are compared with the results of Monte Carlo simulation.

Voltage dependence of a stochastic model of activation of an alpha helical S4 sensor in a K channel membrane

NASA Astrophysics Data System (ADS)

Vaccaro, S. R.

2011-09-01

The voltage dependence of the ionic and gating currents of a K channel is dependent on the activation barriers of a voltage sensor with a potential function which may be derived from the principal electrostatic forces on an S4 segment in an inhomogeneous dielectric medium. By variation of the parameters of a voltage-sensing domain model, consistent with x-ray structures and biophysical data, the lowest frequency of the survival probability of each stationary state derived from a solution of the Smoluchowski equation provides a good fit to the voltage dependence of the slowest time constant of the ionic current in a depolarized membrane, and the gating current exhibits a rising phase that precedes an exponential relaxation. For each depolarizing potential, the calculated time dependence of the survival probabilities of the closed states of an alpha helical S4 sensor are in accord with an empirical model of the ionic and gating currents recorded during the activation process.

Experimental techniques for the calibration of lidar depolarization channels in EARLINET

NASA Astrophysics Data System (ADS)

Belegante, Livio; Bravo-Aranda, Juan Antonio; Freudenthaler, Volker; Nicolae, Doina; Nemuc, Anca; Ene, Dragos; Alados-Arboledas, Lucas; Amodeo, Aldo; Pappalardo, Gelsomina; D'Amico, Giuseppe; Amato, Francesco; Engelmann, Ronny; Baars, Holger; Wandinger, Ulla; Papayannis, Alexandros; Kokkalis, Panos; Pereira, Sérgio N.

2018-02-01

Particle depolarization ratio retrieved from lidar measurements are commonly used for aerosol-typing studies, microphysical inversion, or mass concentration retrievals. The particle depolarization ratio is one of the primary parameters that can differentiate several major aerosol components but only if the measurements are accurate enough. The accuracy related to the retrieval of particle depolarization ratios is the driving factor for assessing and improving the uncertainties of the depolarization products. This paper presents different depolarization calibration procedures used to improve the quality of the depolarization data. The results illustrate a significant improvement of the depolarization lidar products for all the selected lidar stations that have implemented depolarization calibration procedures. The calibrated volume and particle depolarization profiles at 532 nm show values that fall within a range that is generally accepted in the literature.

He 3 -Xe 129 Comagnetometery using Rb 87 Detection and Decoupling

NASA Astrophysics Data System (ADS)

Limes, M. E.; Sheng, D.; Romalis, M. V.

2018-01-01

We describe a He 3 -Xe 129 comagnetometer using Rb 87 atoms for noble-gas spin polarization and detection. We use a train of Rb 87 π pulses and σ+/σ- optical pumping to realize a finite-field Rb magnetometer with suppression of spin-exchange relaxation. We suppress frequency shifts from polarized Rb by measuring the He 3 and Xe 129 spin precession frequencies in the dark, while applying π pulses along two directions to depolarize Rb atoms. The plane of the π pulses is rotated to suppress the Bloch-Siegert shifts for the nuclear spins. We measure the ratio of He 3 to Xe 129 spin precession frequencies with sufficient absolute accuracy to resolve Earth's rotation without changing the orientation of the comagnetometer. A frequency resolution of 7 nHz is achieved after integration for 8 h without evidence of significant drift.

Ca(2+)-activated anion channels and membrane depolarizations induced by blue light and cold in Arabidopsis seedlings

NASA Technical Reports Server (NTRS)

Lewis, B. D.; Karlin-Neumann, G.; Davis, R. W.; Spalding, E. P.; Evans, M. L. (Principal Investigator)

1997-01-01

The activation of an anion channel in the plasma membrane of Arabidopsis thaliana hypocotyls by blue light (BL) is believed to be a signal-transducing event leading to growth inhibition. Here we report that the open probability of this particular anion channel depends on cytoplasmic Ca2+ ([Ca2+]cyt) within the concentration range of 1 to 10 microM, raising the possibility that BL activates the anion channel by increasing [Ca2+]cyt. Arabidopsis seedlings cytoplasmically expressing aequorin were generated to test this possibility. Aequorin luminescence did not increase during or after BL, providing evidence that Ca2+ does not play a second-messenger role in the activation of anion channels. However, cold shock simultaneously triggered a large increase in [Ca2+]cyt and a 110-mV transient depolarization of the plasma membrane. A blocker of the anion channel, 5-nitro-2-(3-phenylpropylamino)-benzoic acid, blocked 61% of the cold-induced depolarization without affecting the increase in [Ca2+]cyt. These data led us to propose that cold shock opens Ca2+ channels at the plasma membrane, allowing an inward, depolarizing Ca2+ current. The resulting large increase in [Ca2+]cyt activates the anion channel, which further depolarizes the membrane. Although an increase in [Ca2+]cyt may activate anion channels in response to cold, it appears that BL does so via a Ca(2+)-independent pathway.

Enhanced fast-inactivated state stability of cardiac sodium channels by a novel voltage sensor SCN5A mutation, R1632C, as a cause of atypical Brugada syndrome.

PubMed

Nakajima, Tadashi; Kaneko, Yoshiaki; Saito, Akihiro; Ota, Masaki; Iijima, Takafumi; Kurabayashi, Masahiko

2015-11-01

Mutations in SCN5A, which encodes the cardiac voltage-gated sodium channels, can be associated with multiple electrophysiological phenotypes. A novel SCN5A R1632C mutation, located in the domain IV-segment 4 voltage sensor, was identified in a young male patient who had a syncopal episode during exercise and presented with atrial tachycardia, sinus node dysfunction, and Brugada syndrome. We sought to elucidate the functional consequences of the R1632C mutation. The wild-type (WT) or R1632C SCN5A mutation was coexpressed with β1 subunit in tsA201 cells, and whole-cell sodium currents (INa) were recorded using patch-clamp methods. INa density, measured at -20 mV from a holding potential of -120 mV, for R1632C was significantly lower than that for WT (R1632C: -433 ± 52 pA/pF, n = 14; WT: -672 ± 90 pA/pF, n = 15; P < .05); however, no significant changes were observed in the steady-state activation and fast inactivation rate. The steady-state inactivation curve for R1632C was remarkably shifted to hyperpolarizing potentials compared with that for WT (R1632C: V1/2 = -110.7 ± 0.8 mV, n = 16; WT: V1/2 = -85.9 ± 2.5 mV, n = 17; P < .01). The steady-state fast inactivation curve for R1632C was also shifted to the same degree. Recovery from fast inactivation after a 20-ms depolarizing pulse for R1632C was remarkably delayed compared with that for WT (R1632C: τ = 246.7 ± 14.3 ms, n = 8; WT: τ = 3.7 ± 0.3 ms, n = 8; P < .01). Repetitive depolarizing pulses at various cycle lengths greatly attenuated INa for R1632C than that for WT. R1632C showed a loss of function of INa by an enhanced fast-inactivated state stability because of a pronounced impairment of recovery from fast inactivation, which may explain the phenotypic manifestation observed in our patient. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Depolarization Diffusion During Weak Suprathreshold Stimulation of Cardiac Tissue

DTIC Science & Technology

2001-10-25

DEPOLARIZATION DIFFUSION DURING WEAK SUPRATHRESHOLD STIMULATION OF CARDIAC TISSUE Vladimir Nikolski, Aleksandre Sambelashvili, and Igor R. Efimov...the depolarized regions. Such an activation pattern appears similar to break activation. The effect of the depolarization diffusion from depolarized...Subtitle Depolarization Diffusion During Weak Suprathreshold Stimulation of Cardiac Tissue Contract Number Grant Number Program Element Number Author(s

Collision-induced stimulated photon echoes in ‘strong’ magnetic field

NASA Astrophysics Data System (ADS)

Reshetov, V. A.

2018-05-01

Collision-induced stimulated photon echoes formed in a gaseous medium on the transition with the angular momentum change Ja=0 → Jb=1 under the action of ‘strong’ longitudinal magnetic field, when the echo pulse becomes unpolarized, are considered with an account of elastic depolarizing collisions. In the case of narrow spectral line the explicit expressions for the echo polarization density matrix and the degree of polarization are obtained. In the case of broad spectral line the results of the numeric calculations reproduce qualitatively the curve obtained in the experiments with ytterbium vapor.

Accumulation of K+ in the synaptic cleft modulates activity by influencing both vestibular hair cell and calyx afferent in the turtle

PubMed Central

Contini, Donatella; Price, Steven D.

2016-01-01

Key points In the synaptic cleft between type I hair cells and calyceal afferents, K+ ions accumulate as a function of activity, dynamically altering the driving force and permeation through ion channels facing the synaptic cleft.High‐fidelity synaptic transmission is possible due to large conductances that minimize hair cell and afferent time constants in the presence of significant membrane capacitance.Elevated potassium maintains hair cells near a potential where transduction currents are sufficient to depolarize them to voltages necessary for calcium influx and synaptic vesicle fusion.Elevated potassium depolarizes the postsynaptic afferent by altering ion permeation through hyperpolarization‐activated cyclic nucleotide‐gated (HCN) channels, and contributes to depolarizing the afferent to potentials where a single EPSP (quantum) can generate an action potential.With increased stimulation, hair cell depolarization increases the frequency of quanta released, elevates [K+]cleft and depolarizes the afferent to potentials at which smaller and smaller EPSPs would be sufficient to trigger APs. Abstract Fast neurotransmitters act in conjunction with slower modulatory effectors that accumulate in restricted synaptic spaces found at giant synapses such as the calyceal endings in the auditory and vestibular systems. Here, we used dual patch‐clamp recordings from turtle vestibular hair cells and their afferent neurons to show that potassium ions accumulating in the synaptic cleft modulated membrane potentials and extended the range of information transfer. High‐fidelity synaptic transmission was possible due to large conductances that minimized hair cell and afferent time constants in the presence of significant membrane capacitance. Increased potassium concentration in the cleft maintained the hair cell near potentials that promoted the influx of calcium necessary for synaptic vesicle fusion. The elevated potassium concentration also depolarized the postsynaptic neuron by altering ion permeation through hyperpolarization‐activated cyclic nucleotide‐gated (HCN) channels. This depolarization enabled the afferent to reliably generate action potentials evoked by single AMPA‐dependent EPSPs. Depolarization of the postsynaptic afferent could also elevate potassium in the synaptic cleft, and would depolarize other hair cells enveloped by the same neuritic process increasing the fidelity of neurotransmission at those synapses as well. Collectively, these data demonstrate that neuronal activity gives rise to potassium accumulation, and suggest that potassium ion action on HCN channels can modulate neurotransmission, preserving the fidelity of high‐speed synaptic transmission by dynamically shifting the resting potentials of both presynaptic and postsynaptic cells. PMID:27633787

A positive feedback at the cellular level promotes robustness and modulation at the circuit level

PubMed Central

Dethier, Julie; Drion, Guillaume; Franci, Alessio

2015-01-01

This article highlights the role of a positive feedback gating mechanism at the cellular level in the robustness and modulation properties of rhythmic activities at the circuit level. The results are presented in the context of half-center oscillators, which are simple rhythmic circuits composed of two reciprocally connected inhibitory neuronal populations. Specifically, we focus on rhythms that rely on a particular excitability property, the postinhibitory rebound, an intrinsic cellular property that elicits transient membrane depolarization when released from hyperpolarization. Two distinct ionic currents can evoke this transient depolarization: a hyperpolarization-activated cation current and a low-threshold T-type calcium current. The presence of a slow activation is specific to the T-type calcium current and provides a slow positive feedback at the cellular level that is absent in the cation current. We show that this slow positive feedback is required to endow the network rhythm with physiological modulation and robustness properties. This study thereby identifies an essential cellular property to be retained at the network level in modeling network robustness and modulation. PMID:26311181

Calcium current in type I hair cells isolated from the semicircular canal crista ampullaris of the rat.

PubMed

Almanza, Angélica; Vega, Rosario; Soto, Enrique

2003-12-24

The low voltage gain in type I hair cells implies that neurotransmitter release at their afferent synapse should be mediated by low voltage activated calcium channels, or that some peculiar mechanism should be operating in this synapse. With the patch clamp technique, we studied the characteristics of the Ca(2+) current in type I hair cells enzymatically dissociated from rat semicircular canal crista ampullaris. Calcium current in type I hair cells exhibited a slow inactivation (during 2-s depolarizing steps), was sensitive to nimodipine and was blocked by Cd(2+) and Ni(2+). This current was activated at potentials above -60 mV, had a mean half maximal activation of -36 mV, and exhibited no steady-state inactivation at holding potentials between -100 and -60 mV. This data led us to conclude that hair cell Ca(2+) current is most likely of the L type. Thus, other mechanisms participating in neurotransmitter release such as K(+) accumulation in the synaptic cleft, modulation of K(+) currents by nitric oxide, participation of a Na(+) current and possible metabotropic cascades activated by depolarization should be considered.

Vitamin K modulates cardiac action potential by blocking sodium and potassium ion channels.

PubMed

Drolet, B; Emond, A; Fortin, V; Daleau, P; Rousseau, G; Cardinal, R; Turgeon, J

2000-10-01

Cardiovascular collapses, syncopes, and sudden deaths have been observed following the rapid administration of intravenous vitamin K. Our objectives were to characterize the effects of vitamin K on cardiac action potentials and to evaluate effects of vitamin K on sodium and potassium currents, namely I(Na), I(Kr), and I(Ks). Guinea pig hearts (n = 21) were paced at a cycle length of 250 msec and exposed to vitamin K at 1.15-4.6 micromol/L (2.5-10 mg/L). Monophasic action potential duration measured at 90% repolarization (MAPD(90)) was not significantly reduced (-1.6 +/- 0.3 msec; P >.05; N.S.) at 1.15 micromol/L, but increased by 6.5 +/- 0.4 msec (P <.05) at 2.3 micromol/L. MAPD(90) was not measurable at 4.6 micromol/L, as a result of inexcitability. Patch-clamp experiments in ventricular myocytes demonstrated a approximately 50% reduction in I(Na) by 10 micromol/L vitamin K and a concentration-dependent reduction of the K(+) current elicited by short depolarizations (250 msec; I(K250)). Estimated IC(50) for I(K250), mostly representing I(Kr), was 2.3 micromol/L. Vitamin K was less potent to block the K(+) current elicited by long depolarizations (5,000 msec; I(K5000)), mostly representing I(Ks), with an estimated IC(50) over 100 micromol/L. Therapeutic concentrations ( approximately 1.5 micromol/L) of intravenous vitamin K modulate cardiac action potential by blocking ionic currents involved in cardiac depolarization and repolarization.

Changes by short-term hypoxia in the membrane properties of pyramidal cells and the levels of purine and pyrimidine nucleotides in slices of rat neocortex; effects of agonists and antagonists of ATP-dependent potassium channels.

PubMed

Pissarek, M; Garcia de Arriba, S; Schäfer, M; Sieler, D; Nieber, K; Illes, P

1998-10-01

In a first series of experiments, intracellular recordings were made from pyramidal cells in layers II-III of the rat primary somatosensory cortex. Superfusion of the brain slice preparations with hypoxic medium (replacement of 95%O2-5%CO2 with 95%N2-5%CO2) for up to 30 min led to a time-dependent depolarization (HD) without a major change in input resistance. Short periods of hypoxia (5 min) induced reproducible depolarizations which were concentration-dependently depressed by an agonist of ATP-dependent potassium (K(ATP)) channels, diazoxide (3-300 microM). The effect of 30 but not 300 microM diazoxide was reversed by washout. Tolbutamide (300 microM), an antagonist of K(ATP) channels, did not alter the HD when given alone. It did, however, abolish the inhibitory effect of diazoxide (30 microM) on the HD. Neither diazoxide (3-300 microM) nor tolbutamide (300 microM) influenced the membrane potential or the apparent input resistance of the neocortical pyramidal cells. Current-voltage (I-V) curves constructed at a membrane potential of -90 mV by injecting both de- and hyperpolarizing current pulses were not altered by diazoxide (30 microM) or tolbutamide (300 microM). Moreover, normoxic and hypoxic I-V curves did not cross each other, excluding a reversal of the HD at any membrane potential between -130 and -50 mV. The hypoxia-induced change of the I-V relation was the same both in the absence and presence of tolbutamide (300 microM). In a second series of experiments, nucleoside di- and triphosphates separated with anion exchange HPLC were measured in the neocortical slices. After 5 min of hypoxia, levels of nucleoside triphosphates declined by 29% (GTP), 34% (ATP), 44% (UTP) and 58% (CTP). By contrast, the levels of nucleoside diphosphates either did not change (UDP) or increased by 13% (GDP) and 40% (ADP). In slices subjected to 30 min of hypoxia the triphosphate levels continued to decrease, while the levels of GDP and ADP returned to control values. The tri- to diphosphate ratios progressively declined for ATP/ADP and GTP/GDP, but not for UTP/UDP when the duration of hypoxia was increased from 5 to 30 min. Hence, the rapid fall in the ratios of nucleoside tri- to diphosphates without the induction of a potassium current failed to indicate an allosteric regulation of a plasmalemmal K(ATP) channel by purine and pyrimidine nucleotides. Diazoxide had no effect on neocortical pyramidal neurons and was effective only in combination with a hypoxic stimulus; it is suggested that both plasmalemmal and mitochondrial K(ATP) channels are involved under these conditions. The hypoxic depolarization may be due to blockade of K+,Na+-ATPase by limitation of energy supplying substrate.

The tetravalent organic cation spermine causes the gating of the IRK1 channel expressed in murine fibroblast cells.

PubMed Central

Ishihara, K; Hiraoka, M; Ochi, R

1996-01-01

1. The activation kinetics of the IRK1 channel stably expressed in L cells (a murine fibroblast cell line) were studied under the whole-cell voltage clamp. Without polyamines or Mg2+ in the pipettes, inward currents showed an exponential activation on hyperpolarization. The steep inward rectification of the currents around the reversal potential (Erev) could be described by the open-close transition of the channel with first-order kinetics. 2. When the tetravalent organic cation spermine (Spm) was added in the pipettes, the activation kinetics changed; this was explicable by the increase in the closing rate constant. The activation of the currents observed without Spm or Mg2+ in the pipettes was ascribed to the unblocking of the 'endogenous-Spm block'. 3. In the presence of the divalent cation putrescine (Put) or of Mg2+ in the pipettes, a different non-conductive state suppressed the outward currents on depolarization; the channels instantaneously changed to the open state on repolarization. As the depolarization was prolonged, this non-conductive state was replaced by the non-conductive state that shows an exponential activation on repolarization. This phenomenon was attributed to the redistribution of the channels from the Put- or Mg(2+)-blocked state to the 'endogenous Spm-blocked state' during depolarization. 4. In the presence of the trivalent cation spermidine (Spd) in the pipettes, two different non-conductive states occurred, showing a faster and a slower activation on repolarization. The rectification around Erev was mainly due to the non-conductive state showing a faster activation, which appeared to be the Spd-blocked state. During depolarization, redistribution of the channels to the 'endogenous Spm-blocked state' also occurred. 5. In the presence of Spd, Put or Mg2+ in the pipettes, the voltage dependence of the activation time constant reflecting the unblocking of the 'endogenous Spm' was shifted in the hyperpolarizing direction. 6. Our results suggest that the 'intrinsic gating' that shows the time-dependent activation on repolarization, and that is responsible for the inward rectification around Erev, reflects the blocking kinetics of the tetravalent Spm. PMID:8866861

Two forms of electrical resonance at theta frequencies, generated by M-current, h-current and persistent Na+ current in rat hippocampal pyramidal cells

PubMed Central

Hu, Hua; Vervaeke, Koen; Storm, Johan F

2002-01-01

Coherent network oscillations in the brain are correlated with different behavioural states. Intrinsic resonance properties of neurons provide a basis for such oscillations. In the hippocampus, CA1 pyramidal neurons show resonance at theta (θ) frequencies (2-7 Hz). To study the mechanisms underlying θ-resonance, we performed whole-cell recordings from CA1 pyramidal cells (n = 73) in rat hippocampal slices. Oscillating current injections at different frequencies (ZAP protocol), revealed clear resonance with peak impedance at 2-5 Hz at ≈33 °C (increasing to ≈7 Hz at ≈38 °C). The θ-resonance showed a U-shaped voltage dependence, being strong at subthreshold, depolarized (≈-60 mV) and hyperpolarized (≈-80 mV) potentials, but weaker near the resting potential (-72 mV). Voltage clamp experiments revealed three non-inactivating currents operating in the subthresold voltage range: (1) M-current (IM), which activated positive to -65 mV and was blocked by the M/KCNQ channel blocker XE991 (10 μm); (2) h-current (Ih), which activated negative to -65 mV and was blocked by the h/HCN channel blocker ZD7288 (10 μm); and (3) a persistent Na+ current (INaP), which activated positive to -65 mV and was blocked by tetrodotoxin (TTX, 1 μm). In current clamp, XE991 or TTX suppressed the resonance at depolarized, but not hyperpolarized membrane potentials, whereas ZD7288 abolished the resonance only at hyperpolarized potentials. We conclude that these cells show two forms of θ-resonance: ‘M-resonance’ generated by the M-current and persistent Na+ current in depolarized cells, and ‘H-resonance’ generated by the h-current in hyperpolarized cells. Computer simulations supported this interpretation. These results suggest a novel function for M/KCNQ channels in the brain: to facilitate neuronal resonance and network oscillations in cortical neurons, thus providing a basis for an oscillation-based neural code. PMID:12482886

Differential inhibition of N and P/Q Ca2+ currents by 5-HT1A and 5-HT1D receptors in spinal neurons of Xenopus larvae

PubMed Central

Sun, Qian-Quan; Dale, Nicholas

1998-01-01

In whole-cell patch clamp recordings made from non-sensory neurons acutely isolated from the spinal cord of Xenopus (stage 40–42) larvae, two forms of inhibition of the high voltage-activated (HVA) Ca2+ currents were produced by 5-HT. One was voltage dependent and associated with both slowing of the activation kinetics and shifting of the voltage dependence of the HVA currents. This inhibition was relieved by strong depolarizing prepulses. A second form of inhibition was neither associated with slowing of the activation kinetics nor relieved by depolarizing prepulses and was thus voltage independent. In all neurons examined, 5-HT (1 μM) reversibly reduced 34 ± 1.6 % (n = 102) of the HVA Ca2+ currents. In about 40 % of neurons, the inhibition was totally voltage independent. In another 5 %, the inhibition was totally voltage dependent. In the remaining neurons, inhibition was only partially (by around 40 %) relieved by a large depolarizing prepulse, suggesting that in these, the inhibition consisted of both voltage-dependent and -independent components. By using selective channel blockers, we found that 5-HT acted on both N- and P/Q-type channels. However, whereas the inhibition of P/Q-type currents was only voltage independent, the inhibition of N-type currents had both voltage-dependent and -independent components. The effects of 5-HT on HVA Ca2+ currents were mediated by 5-HT1A and 5-HT1D receptors. The 5-HT1A receptors not only preferentially caused voltage-independent inhibition, but did so by acting mainly on the ω-agatoxin-IVA-sensitive Ca2+ channels. In contrast, the 5-HT1D receptor produced both voltage-dependent and -independent inhibition and was preferentially coupled to ω-conotoxin-GVIA sensitive channels. This complexity of modulation may allow fine tuning of transmitter release and calcium signalling in the spinal circuitry of Xenopus larvae. PMID:9625870

Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP) and Endolysosomal Two-pore Channels Modulate Membrane Excitability and Stimulus-Secretion Coupling in Mouse Pancreatic β Cells*

PubMed Central

Arredouani, Abdelilah; Ruas, Margarida; Collins, Stephan C.; Parkesh, Raman; Clough, Frederick; Pillinger, Toby; Coltart, George; Rietdorf, Katja; Royle, Andrew; Johnson, Paul; Braun, Matthias; Zhang, Quan; Sones, William; Shimomura, Kenju; Morgan, Anthony J.; Lewis, Alexander M.; Chuang, Kai-Ting; Tunn, Ruth; Gadea, Joaquin; Teboul, Lydia; Heister, Paula M.; Tynan, Patricia W.; Bellomo, Elisa A.; Rutter, Guy A.; Rorsman, Patrik; Churchill, Grant C.; Parrington, John; Galione, Antony

2015-01-01

Pancreatic β cells are electrically excitable and respond to elevated glucose concentrations with bursts of Ca2+ action potentials due to the activation of voltage-dependent Ca2+ channels (VDCCs), which leads to the exocytosis of insulin granules. We have examined the possible role of nicotinic acid adenine dinucleotide phosphate (NAADP)-mediated Ca2+ release from intracellular stores during stimulus-secretion coupling in primary mouse pancreatic β cells. NAADP-regulated Ca2+ release channels, likely two-pore channels (TPCs), have recently been shown to be a major mechanism for mobilizing Ca2+ from the endolysosomal system, resulting in localized Ca2+ signals. We show here that NAADP-mediated Ca2+ release from endolysosomal Ca2+ stores activates inward membrane currents and depolarizes the β cell to the threshold for VDCC activation and thereby contributes to glucose-evoked depolarization of the membrane potential during stimulus-response coupling. Selective pharmacological inhibition of NAADP-evoked Ca2+ release or genetic ablation of endolysosomal TPC1 or TPC2 channels attenuates glucose- and sulfonylurea-induced membrane currents, depolarization, cytoplasmic Ca2+ signals, and insulin secretion. Our findings implicate NAADP-evoked Ca2+ release from acidic Ca2+ storage organelles in stimulus-secretion coupling in β cells. PMID:26152717

Noise Enhances Action Potential Generation in Mouse Sensory Neurons via Stochastic Resonance.

PubMed

Onorato, Irene; D'Alessandro, Giuseppina; Di Castro, Maria Amalia; Renzi, Massimiliano; Dobrowolny, Gabriella; Musarò, Antonio; Salvetti, Marco; Limatola, Cristina; Crisanti, Andrea; Grassi, Francesca

2016-01-01

Noise can enhance perception of tactile and proprioceptive stimuli by stochastic resonance processes. However, the mechanisms underlying this general phenomenon remain to be characterized. Here we studied how externally applied noise influences action potential firing in mouse primary sensory neurons of dorsal root ganglia, modelling a basic process in sensory perception. Since noisy mechanical stimuli may cause stochastic fluctuations in receptor potential, we examined the effects of sub-threshold depolarizing current steps with superimposed random fluctuations. We performed whole cell patch clamp recordings in cultured neurons of mouse dorsal root ganglia. Noise was added either before and during the step, or during the depolarizing step only, to focus onto the specific effects of external noise on action potential generation. In both cases, step + noise stimuli triggered significantly more action potentials than steps alone. The normalized power norm had a clear peak at intermediate noise levels, demonstrating that the phenomenon is driven by stochastic resonance. Spikes evoked in step + noise trials occur earlier and show faster rise time as compared to the occasional ones elicited by steps alone. These data suggest that external noise enhances, via stochastic resonance, the recruitment of transient voltage-gated Na channels, responsible for action potential firing in response to rapid step-wise depolarizing currents.

Capacitance measurements of regulated exocytosis in mouse taste cells.

PubMed

Vandenbeuch, Aurelie; Zorec, Robert; Kinnamon, Sue C

2010-11-03

Exocytosis, consisting of the merger of vesicle and plasma membrane, is a common mechanism used by different types of nucleated cells to release their vesicular contents. Taste cells possess vesicles containing various neurotransmitters to communicate with adjacent taste cells and afferent nerve fibers. However, whether these vesicles engage in exocytosis on a stimulus is not known. Since vesicle membrane merger with the plasma membrane is reflected in plasma membrane area fluctuations, we measured membrane capacitance (C(m)), a parameter linearly related to membrane surface area. To investigate whether taste cells undergo regulated exocytosis, we used the compensated tight-seal whole-cell recording technique to monitor depolarization-induced changes in C(m) in the different types of taste cells. To identify taste cell types, mice expressing green fluorescent protein from the TRPM5 promoter or from the GAD67 promoter were used to discriminate type II and type III taste cells, respectively. Moreover, the cell types were also identified by monitoring their voltage-current properties. The results demonstrate that only type III taste cells show significant depolarization-induced increases in C(m), which were correlated to the voltage-activated calcium currents. The results suggest that type III, but neither type II nor type I cells exhibit depolarization-induced regulated exocytosis to release transmitter and activate gustatory afferent nerve fibers.

Noise Enhances Action Potential Generation in Mouse Sensory Neurons via Stochastic Resonance

PubMed Central

Onorato, Irene; D'Alessandro, Giuseppina; Di Castro, Maria Amalia; Renzi, Massimiliano; Dobrowolny, Gabriella; Musarò, Antonio; Salvetti, Marco; Limatola, Cristina; Crisanti, Andrea; Grassi, Francesca

2016-01-01

Noise can enhance perception of tactile and proprioceptive stimuli by stochastic resonance processes. However, the mechanisms underlying this general phenomenon remain to be characterized. Here we studied how externally applied noise influences action potential firing in mouse primary sensory neurons of dorsal root ganglia, modelling a basic process in sensory perception. Since noisy mechanical stimuli may cause stochastic fluctuations in receptor potential, we examined the effects of sub-threshold depolarizing current steps with superimposed random fluctuations. We performed whole cell patch clamp recordings in cultured neurons of mouse dorsal root ganglia. Noise was added either before and during the step, or during the depolarizing step only, to focus onto the specific effects of external noise on action potential generation. In both cases, step + noise stimuli triggered significantly more action potentials than steps alone. The normalized power norm had a clear peak at intermediate noise levels, demonstrating that the phenomenon is driven by stochastic resonance. Spikes evoked in step + noise trials occur earlier and show faster rise time as compared to the occasional ones elicited by steps alone. These data suggest that external noise enhances, via stochastic resonance, the recruitment of transient voltage-gated Na channels, responsible for action potential firing in response to rapid step-wise depolarizing currents. PMID:27525414

Intracellular ca2+ stores could participate to abscisic acid-induced depolarization and stomatal closure in Arabidopsis thaliana

PubMed Central

Meimoun, Patrice; Vidal, Guillaume; Bohrer, Anne-Sophie; Lehner, Arnaud; Tran, Daniel; Briand, Joël; Bouteau, François

2009-01-01

In Arabidopsis thaliana cell suspension,abscisic acid (aBa) induces changes in cytosolic calcium concentration ([Ca2+]cyt) which are the trigger for aBa-induced plasma membrane anion current activation, H+-aTPase inhibition, and subsequent plasma membrane depolarization. In the present study, we took advantage of this model to analyze the implication of intracellular Ca2+ stores in aBa signal transduction through electrophysiological current measurements, cytosolic Ca2+ activity measurements with the apoaequorin Ca2+ reporter protein and external pH measurement. Intracellular Ca2+ stores involvement was determined by using specific inhibitors of CICR channels: the cADP-ribose/ryanodine receptor (Br-cADPR and dantrolene) and of the inositol trisphosphate receptor (U73122). In addition experiments were performed on epidermal strips of A. thaliana leaves to monitor stomatal closure in response to ABA in presence of the same pharmacology. Our data provide evidence that ryanodine receptor and inositol trisphosphate receptor could be involved in ABA-induced (1) Ca2+ release in the cytosol, (2) anion channel activation and H+-ATPase inhibition leading to plasma membrane depolarization and (3) stomatal closure. Intracellular Ca2+ release could thus contribute to the control of early events in the ABA signal transduction pathway in A. thaliana. PMID:19847112

Unitary IPSPs evoked by interneurons at the stratum radiatum-stratum lacunosum-moleculare border in the CA1 area of the rat hippocampus in vitro

PubMed Central

Vida, Imre; Halasy, Katalin; Szinyei, Csaba; Somogyi, Peter; Buhl, Eberhard H

1998-01-01

Hippocampal non-principal neurons at the stratum radiatum-stratum lacunosum-moleculare border (R-LM interneurons) of the CA1 area may constitute several cell classes and have been implicated in the generation of GABAergic unitary IPSPs. Using biocytin-filled electrodes we recorded R-LM interneurons intracellularly in vitro and determined their postsynaptic effects in concomitantly recorded pyramidal cells. Light microscopic analysis revealed four populations of R-LM interneurons with distinct axons: (1) basket cells (n= 4) with axons predominantly ramifying in the pyramidal cell layer; (2) Schaffer collateral/commissural pathway-associated interneurons (n= 10) stratifying in stratum radiatum and, to a lesser extent, stratum oriens; (3) perforant pathway-associated interneurons (n= 6) innervating the perforant path termination zone in stratum lacunosum-moleculare of the CA1 area as well as equivalent portions of the dentate gyrus and subiculum; and (4) neurogliaform interneurons (n= 2) characterized by their dense, compact axonal and dendritic arbour. Random electron microscopic sampling of synaptic targets revealed a preponderance of pyramidal neurons as postsynaptic elements. Basket cells had a synaptic target preference for somata and proximal dendrites, whereas the remainder of R-LM interneurons innervated dendritic shafts and spines. The axon of dendrite-targeting cells formed up to six putative contacts with individual postsynaptic pyramidal cells. Anatomically recovered R-LM interneurons (n= 22) had a mean resting membrane potential of -56.7 ± 3.6 mV, a membrane time constant of 12.9 ± 7.7 ms and an input resistance of 86.4 ± 29.2 MΩ. Depolarizing current pulses generally elicited overshooting action potentials (70.8 ± 6.9 mV) which had a mean duration, when measured at half-amplitude, of 0.7 ± 0.1 ms. In response to prolonged (> 200 ms) depolarizing current pulses all R-LM interneurons displayed (a varying degree of) spike frequency adaptation. Basket cells, Schaffer-associated and neurogliaform interneurons elicited small-amplitude (< 2 mV), short-latency IPSPs in postsynaptic pyramids (n= 5, 13 and 1, respectively). Those interactions in which an effect was elicited with the repetitive activation of the presynaptic neuron (n= 13) showed a substantial degree of postsynaptic response summation. Unitary IPSPs had fast kinetics and, whenever tested (n= 5; 1 basket cell and 4 Schaffer-associated interneurons), were abolished by the GABAA receptor antagonist bicuculline. Thus, R-LM interneurons comprise several distinct populations which evoke fast GABAA receptor-mediated IPSPs. The domain-specific innervation of postsynaptic pyramidal cells suggests functionally diverse effects on the integration of afferent information in functionally non-equivalent compartments of pyramidal cells. PMID:9503336

Estimating Depolarization with the Jones Matrix Quality Factor

NASA Astrophysics Data System (ADS)

Hilfiker, James N.; Hale, Jeffrey S.; Herzinger, Craig M.; Tiwald, Tom; Hong, Nina; Schöche, Stefan; Arwin, Hans

2017-11-01

Mueller matrix (MM) measurements offer the ability to quantify the depolarization capability of a sample. Depolarization can be estimated using terms such as the depolarization index or the average degree of polarization. However, these calculations require measurement of the complete MM. We propose an alternate depolarization metric, termed the Jones matrix quality factor, QJM, which does not require the complete MM. This metric provides a measure of how close, in a least-squares sense, a Jones matrix can be found to the measured Mueller matrix. We demonstrate and compare the use of QJM to other traditional calculations of depolarization for both isotropic and anisotropic depolarizing samples; including non-uniform coatings, anisotropic crystal substrates, and beetle cuticles that exhibit both depolarization and circular diattenuation.

Seizure-induced alterations in fast-spiking basket cell GABA currents modulate frequency and coherence of gamma oscillation in network simulations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Proddutur, Archana; Yu, Jiandong; Elgammal, Fatima S.

2013-12-15

Gamma frequency oscillations have been proposed to contribute to memory formation and retrieval. Fast-spiking basket cells (FS-BCs) are known to underlie development of gamma oscillations. Fast, high amplitude GABA synapses and gap junctions have been suggested to contribute to gamma oscillations in FS-BC networks. Recently, we identified that, apart from GABAergic synapses, FS-BCs in the hippocampal dentate gyrus have GABAergic currents mediated by extrasynaptic receptors. Our experimental studies demonstrated two specific changes in FS-BC GABA currents following experimental seizures [Yu et al., J. Neurophysiol. 109, 1746 (2013)]: increase in the magnitude of extrasynaptic (tonic) GABA currents and a depolarizing shiftmore » in GABA reversal potential (E{sub GABA}). Here, we use homogeneous networks of a biophysically based model of FS-BCs to examine how the presence of extrasynaptic GABA conductance (g{sub GABA-extra}) and experimentally identified, seizure-induced changes in g{sub GABA-extra} and E{sub GABA} influence network activity. Networks of FS-BCs interconnected by fast GABAergic synapses developed synchronous firing in the dentate gamma frequency range (40–100 Hz). Systematic investigation revealed that the biologically realistic range of 30 to 40 connections between FS-BCs resulted in greater coherence in the gamma frequency range when networks were activated by Poisson-distributed dendritic synaptic inputs rather than by homogeneous somatic current injections, which were balanced for FS-BC firing frequency in unconnected networks. Distance-dependent conduction delay enhanced coherence in networks with 30–40 FS-BC interconnections while inclusion of gap junctional conductance had a modest effect on coherence. In networks activated by somatic current injections resulting in heterogeneous FS-BC firing, increasing g{sub GABA-extra} reduced the frequency and coherence of FS-BC firing when E{sub GABA} was shunting (−74 mV), but failed to alter average FS-BC frequency when E{sub GABA} was depolarizing (−54 mV). When FS-BCs were activated by biologically based dendritic synaptic inputs, enhancing g{sub GABA-extra} reduced the frequency and coherence of FS-BC firing when E{sub GABA} was shunting and increased average FS-BC firing when E{sub GABA} was depolarizing. Shifting E{sub GABA} from shunting to depolarizing potentials consistently increased network frequency to and above high gamma frequencies (>80 Hz). Since gamma oscillations may contribute to learning and memory processing [Fell et al., Nat. Neurosci. 4, 1259 (2001); Jutras et al., J. Neurosci. 29, 12521 (2009); Wang, Physiol. Rev. 90, 1195 (2010)], our demonstration that network oscillations are modulated by extrasynaptic inhibition in FS-BCs suggests that neuroactive compounds that act on extrasynaptic GABA receptors could impact memory formation by modulating hippocampal gamma oscillations. The simulation results indicate that the depolarized FS-BC GABA reversal, observed after experimental seizures, together with enhanced spillover extrasynaptic GABA currents are likely to promote generation of focal high frequency activity associated with epileptic networks.« less

Response repetition biases in human perceptual decisions are explained by activity decay in competitive attractor models

PubMed Central

Bonaiuto, James J; de Berker, Archy; Bestmann, Sven

2016-01-01

Animals and humans have a tendency to repeat recent choices, a phenomenon known as choice hysteresis. The mechanism for this choice bias remains unclear. Using an established, biophysically informed model of a competitive attractor network for decision making, we found that decaying tail activity from the previous trial caused choice hysteresis, especially during difficult trials, and accurately predicted human perceptual choices. In the model, choice variability could be directionally altered through amplification or dampening of post-trial activity decay through simulated depolarizing or hyperpolarizing network stimulation. An analogous intervention using transcranial direct current stimulation (tDCS) over left dorsolateral prefrontal cortex (dlPFC) yielded a close match between model predictions and experimental results: net soma depolarizing currents increased choice hysteresis, while hyperpolarizing currents suppressed it. Residual activity in competitive attractor networks within dlPFC may thus give rise to biases in perceptual choices, which can be directionally controlled through non-invasive brain stimulation. DOI: http://dx.doi.org/10.7554/eLife.20047.001 PMID:28005007

Membrane potential bistability in nonexcitable cells as described by inward and outward voltage-gated ion channels.

PubMed

Cervera, Javier; Alcaraz, Antonio; Mafe, Salvador

2014-10-30

The membrane potential of nonexcitable cells, defined as the electrical potential difference between the cell cytoplasm and the extracellular environment when the current is zero, is controlled by the individual electrical conductance of different ion channels. In particular, inward- and outward-rectifying voltage-gated channels are crucial for cell hyperpolarization/depolarization processes, being amenable to direct physical study. High (in absolute value) negative membrane potentials are characteristic of terminally differentiated cells, while low membrane potentials are found in relatively depolarized, more plastic cells (e.g., stem, embryonic, and cancer cells). We study theoretically the hyperpolarized and depolarized values of the membrane potential, as well as the possibility to obtain a bistability behavior, using simplified models for the ion channels that regulate this potential. The bistability regions, which are defined in the multidimensional state space determining the cell state, can be relevant for the understanding of the different model cell states and the transitions between them, which are triggered by changes in the external environment.

Oxygen availability and spreading depolarizations provide complementary prognostic information in neuromonitoring of aneurysmal subarachnoid hemorrhage patients.

PubMed

Winkler, Maren Kl; Dengler, Nora; Hecht, Nils; Hartings, Jed A; Kang, Eun J; Major, Sebastian; Martus, Peter; Vajkoczy, Peter; Woitzik, Johannes; Dreier, Jens P

2017-05-01

Multimodal neuromonitoring in neurocritical care increasingly includes electrocorticography to measure epileptic events and spreading depolarizations. Spreading depolarization causes spreading depression of activity (=isoelectricity) in electrically active tissue. If the depression is long-lasting, further spreading depolarizations occur in still isoelectric tissue where no activity can be suppressed. Such spreading depolarizations are termed isoelectric and are assumed to indicate energy compromise. However, experimental and clinical recordings suggest that long-lasting spreading depolarization-induced depression and isoelectric spreading depolarizations are often recorded outside of the actual ischemic zones, allowing the remote diagnosis of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. Here, we analyzed simultaneous electrocorticography and tissue partial pressure of oxygen recording in 33 aneurysmal subarachnoid hemorrhage patients. Multiple regression showed that both peak total depression duration per recording day and mean baseline tissue partial pressure of oxygen were independent predictors of outcome. Moreover, tissue partial pressure of oxygen preceding spreading depolarization was similar and differences in tissue partial pressure of oxygen responses to spreading depolarization were only subtle between isoelectric spreading depolarizations and spreading depressions. This further supports that, similar to clustering of spreading depolarizations, long spreading depolarization-induced periods of isoelectricity are useful to detect energy compromise remotely, which is valuable because the exact location of future developing pathology is unknown at the time when the neurosurgeon implants recording devices.

Properties of the calcium-activated chloride current in heart.

PubMed

Zygmunt, A C; Gibbons, W R

1992-03-01

We used the whole cell patch clamp technique to study transient outward currents of single rabbit atrial cells. A large transient current, IA, was blocked by 4-aminopyridine (4AP) and/or by depolarized holding potentials. After block of IA, a smaller transient current remained. It was completely blocked by nisoldipine, cadmium, ryanodine, or caffeine, which indicates that all of the 4AP-resistant current is activated by the calcium transient that causes contraction. Neither calcium-activated potassium current nor calcium-activated nonspecific cation current appeared to contribute to the 4AP-resistant transient current. The transient current disappeared when ECl was made equal to the pulse potential; it was present in potassium-free internal and external solutions. It was blocked by the anion transport blockers SITS and DIDS, and the reversal potential of instantaneous current-voltage relations varied with extracellular chloride as predicted for a chloride-selective conductance. We concluded that the 4AP-resistant transient outward current of atrial cells is produced by a calcium-activated chloride current like the current ICl(Ca) of ventricular cells (1991. Circulation Research. 68:424-437). ICl(Ca) in atrial cells demonstrated outward rectification, even when intracellular chloride concentration was higher than extracellular. When ICa was inactivated or allowed to recover from inactivation, amplitudes of ICl(Ca) and ICa were closely correlated. The results were consistent with the view that ICl(Ca) does not undergo independent inactivation. Tentatively, we propose that ICl(Ca) is transient because it is activated by an intracellular calcium transient. Lowering extracellular sodium increased the peak outward transient current. The current was insensitive to the choice of sodium substitute. Because a recently identified time-independent, adrenergically activated chloride current in heart is reduced in low sodium, these data suggest that the two chloride currents are produced by different populations of channels.

Slow Bursting Neurons of Mouse Cortical Layer 6b Are Depolarized by Hypocretin/Orexin and Major Transmitters of Arousal

PubMed Central

Wenger Combremont, Anne-Laure; Bayer, Laurence; Dupré, Anouk; Mühlethaler, Michel; Serafin, Mauro

2016-01-01

Neurons firing spontaneously in bursts in the absence of synaptic transmission have been previously recorded in different layers of cortical brain slices. It has been suggested that such neurons could contribute to the generation of alternating UP and DOWN states, a pattern of activity seen during slow-wave sleep. Here, we show that in layer 6b (L6b), known from our previous studies to contain neurons highly responsive to the wake-promoting transmitter hypocretin/orexin (hcrt/orx), there is a set of neurons, endowed with distinct intrinsic properties, which displayed a strong propensity to fire spontaneously in rhythmic bursts. In response to small depolarizing steps, they responded with a delayed firing of action potentials which, upon higher depolarizing steps, invariably inactivated and were followed by a depolarized plateau potential and a depolarizing afterpotential. These cells also displayed a strong hyperpolarization-activated rectification compatible with the presence of an Ih current. Most L6b neurons with such properties were able to fire spontaneously in bursts. Their bursting activity was of intrinsic origin as it persisted not only in presence of blockers of ionotropic glutamatergic and GABAergic receptors but also in a condition of complete synaptic blockade. However, a small number of these neurons displayed a mix of intrinsic bursting and synaptically driven recurrent UP and DOWN states. Most of the bursting L6b neurons were depolarized and excited by hcrt/orx through a direct postsynaptic mechanism that led to tonic firing and eventually inactivation. Similarly, they were directly excited by noradrenaline, histamine, dopamine, and neurotensin. Finally, the intracellular injection of these cells with dye and their subsequent Neurolucida reconstruction indicated that they were spiny non-pyramidal neurons. These results lead us to suggest that the propensity for slow rhythmic bursting of this set of L6b neurons could be directly impeded by hcrt/orx and other wake-promoting transmitters. PMID:27379007

Responses of photoreceptors in Hermissenda.

PubMed

Akon, D L; Fuortes, M G

1972-12-01

The five photoreceptors in the eye of the mollusc Hermissenda crassicornis respond to light with depolarization and firing of impulses. The impulses of any one cell inhibit other cells, but the degree of inhibition differs in different pairs. Evidence is presented to show that the interactions occur at terminal branches of the photoreceptor axons, inside the cerebropleural ganglion. Properties of the generator potential are examined and it is shown that the depolarization develops in two phases which are affected differently by extrinsic currents. Finally, it is shown that by enhancing the differences in the responses of individual cells to a variety of stimuli, the interactions may facilitate a number of simple discriminations.

Recording, analysis, and interpretation of spreading depolarizations in neurointensive care: Review and recommendations of the COSBID research group.

PubMed

Dreier, Jens P; Fabricius, Martin; Ayata, Cenk; Sakowitz, Oliver W; William Shuttleworth, C; Dohmen, Christian; Graf, Rudolf; Vajkoczy, Peter; Helbok, Raimund; Suzuki, Michiyasu; Schiefecker, Alois J; Major, Sebastian; Winkler, Maren Kl; Kang, Eun-Jeung; Milakara, Denny; Oliveira-Ferreira, Ana I; Reiffurth, Clemens; Revankar, Gajanan S; Sugimoto, Kazutaka; Dengler, Nora F; Hecht, Nils; Foreman, Brandon; Feyen, Bart; Kondziella, Daniel; Friberg, Christian K; Piilgaard, Henning; Rosenthal, Eric S; Westover, M Brandon; Maslarova, Anna; Santos, Edgar; Hertle, Daniel; Sánchez-Porras, Renán; Jewell, Sharon L; Balança, Baptiste; Platz, Johannes; Hinzman, Jason M; Lückl, Janos; Schoknecht, Karl; Schöll, Michael; Drenckhahn, Christoph; Feuerstein, Delphine; Eriksen, Nina; Horst, Viktor; Bretz, Julia S; Jahnke, Paul; Scheel, Michael; Bohner, Georg; Rostrup, Egill; Pakkenberg, Bente; Heinemann, Uwe; Claassen, Jan; Carlson, Andrew P; Kowoll, Christina M; Lublinsky, Svetlana; Chassidim, Yoash; Shelef, Ilan; Friedman, Alon; Brinker, Gerrit; Reiner, Michael; Kirov, Sergei A; Andrew, R David; Farkas, Eszter; Güresir, Erdem; Vatter, Hartmut; Chung, Lee S; Brennan, K C; Lieutaud, Thomas; Marinesco, Stephane; Maas, Andrew Ir; Sahuquillo, Juan; Dahlem, Markus A; Richter, Frank; Herreras, Oscar; Boutelle, Martyn G; Okonkwo, David O; Bullock, M Ross; Witte, Otto W; Martus, Peter; van den Maagdenberg, Arn Mjm; Ferrari, Michel D; Dijkhuizen, Rick M; Shutter, Lori A; Andaluz, Norberto; Schulte, André P; MacVicar, Brian; Watanabe, Tomas; Woitzik, Johannes; Lauritzen, Martin; Strong, Anthony J; Hartings, Jed A

2017-05-01

Spreading depolarizations (SD) are waves of abrupt, near-complete breakdown of neuronal transmembrane ion gradients, are the largest possible pathophysiologic disruption of viable cerebral gray matter, and are a crucial mechanism of lesion development. Spreading depolarizations are increasingly recorded during multimodal neuromonitoring in neurocritical care as a causal biomarker providing a diagnostic summary measure of metabolic failure and excitotoxic injury. Focal ischemia causes spreading depolarization within minutes. Further spreading depolarizations arise for hours to days due to energy supply-demand mismatch in viable tissue. Spreading depolarizations exacerbate neuronal injury through prolonged ionic breakdown and spreading depolarization-related hypoperfusion (spreading ischemia). Local duration of the depolarization indicates local tissue energy status and risk of injury. Regional electrocorticographic monitoring affords even remote detection of injury because spreading depolarizations propagate widely from ischemic or metabolically stressed zones; characteristic patterns, including temporal clusters of spreading depolarizations and persistent depression of spontaneous cortical activity, can be recognized and quantified. Here, we describe the experimental basis for interpreting these patterns and illustrate their translation to human disease. We further provide consensus recommendations for electrocorticographic methods to record, classify, and score spreading depolarizations and associated spreading depressions. These methods offer distinct advantages over other neuromonitoring modalities and allow for future refinement through less invasive and more automated approaches.

Recording, analysis, and interpretation of spreading depolarizations in neurointensive care: Review and recommendations of the COSBID research group

PubMed Central

Fabricius, Martin; Ayata, Cenk; Sakowitz, Oliver W; William Shuttleworth, C; Dohmen, Christian; Graf, Rudolf; Vajkoczy, Peter; Helbok, Raimund; Suzuki, Michiyasu; Schiefecker, Alois J; Major, Sebastian; Winkler, Maren KL; Kang, Eun-Jeung; Milakara, Denny; Oliveira-Ferreira, Ana I; Reiffurth, Clemens; Revankar, Gajanan S; Sugimoto, Kazutaka; Dengler, Nora F; Hecht, Nils; Foreman, Brandon; Feyen, Bart; Kondziella, Daniel; Friberg, Christian K; Piilgaard, Henning; Rosenthal, Eric S; Westover, M Brandon; Maslarova, Anna; Santos, Edgar; Hertle, Daniel; Sánchez-Porras, Renán; Jewell, Sharon L; Balança, Baptiste; Platz, Johannes; Hinzman, Jason M; Lückl, Janos; Schoknecht, Karl; Schöll, Michael; Drenckhahn, Christoph; Feuerstein, Delphine; Eriksen, Nina; Horst, Viktor; Bretz, Julia S; Jahnke, Paul; Scheel, Michael; Bohner, Georg; Rostrup, Egill; Pakkenberg, Bente; Heinemann, Uwe; Claassen, Jan; Carlson, Andrew P; Kowoll, Christina M; Lublinsky, Svetlana; Chassidim, Yoash; Shelef, Ilan; Friedman, Alon; Brinker, Gerrit; Reiner, Michael; Kirov, Sergei A; Andrew, R David; Farkas, Eszter; Güresir, Erdem; Vatter, Hartmut; Chung, Lee S; Brennan, KC; Lieutaud, Thomas; Marinesco, Stephane; Maas, Andrew IR; Sahuquillo, Juan; Dahlem, Markus A; Richter, Frank; Herreras, Oscar; Boutelle, Martyn G; Okonkwo, David O; Bullock, M Ross; Witte, Otto W; Martus, Peter; van den Maagdenberg, Arn MJM; Ferrari, Michel D; Dijkhuizen, Rick M; Shutter, Lori A; Andaluz, Norberto; Schulte, André P; MacVicar, Brian; Watanabe, Tomas; Woitzik, Johannes; Lauritzen, Martin; Strong, Anthony J; Hartings, Jed A

2016-01-01

Spreading depolarizations (SD) are waves of abrupt, near-complete breakdown of neuronal transmembrane ion gradients, are the largest possible pathophysiologic disruption of viable cerebral gray matter, and are a crucial mechanism of lesion development. Spreading depolarizations are increasingly recorded during multimodal neuromonitoring in neurocritical care as a causal biomarker providing a diagnostic summary measure of metabolic failure and excitotoxic injury. Focal ischemia causes spreading depolarization within minutes. Further spreading depolarizations arise for hours to days due to energy supply-demand mismatch in viable tissue. Spreading depolarizations exacerbate neuronal injury through prolonged ionic breakdown and spreading depolarization-related hypoperfusion (spreading ischemia). Local duration of the depolarization indicates local tissue energy status and risk of injury. Regional electrocorticographic monitoring affords even remote detection of injury because spreading depolarizations propagate widely from ischemic or metabolically stressed zones; characteristic patterns, including temporal clusters of spreading depolarizations and persistent depression of spontaneous cortical activity, can be recognized and quantified. Here, we describe the experimental basis for interpreting these patterns and illustrate their translation to human disease. We further provide consensus recommendations for electrocorticographic methods to record, classify, and score spreading depolarizations and associated spreading depressions. These methods offer distinct advantages over other neuromonitoring modalities and allow for future refinement through less invasive and more automated approaches. PMID:27317657

Nickel suppresses the PACAP-induced increase in guinea pig cardiac neuron excitability

PubMed Central

Tompkins, John D.; Merriam, Laura A.; Girard, Beatrice M.; May, Victor

2015-01-01

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a potent intercellular signaling molecule involved in multiple homeostatic functions. PACAP/PAC1 receptor signaling increases excitability of neurons within the guinea pig cardiac ganglia, making them a unique system to establish mechanisms underlying PACAP modulation of neuronal function. Calcium influx is required for the PACAP-increased cardiac neuron excitability, although the pathway is unknown. This study tested whether PACAP enhancement of calcium influx through either T-type or R-type channels contributed to the modulation of excitability. Real-time quantitative polymerase chain reaction analyses indicated transcripts for Cav3.1, Cav3.2, and Cav3.3 T-type isoforms and R-type Cav2.3 in cardiac neurons. These neurons often exhibit a hyperpolarization-induced rebound depolarization that remains when cesium is present to block hyperpolarization-activated nonselective cationic currents (Ih). The T-type calcium channel inhibitors, nickel (Ni2+) or mibefradil, suppressed the rebound depolarization, and treatment with both drugs hyperpolarized cardiac neurons by 2–4 mV. Together, these results are consistent with the presence of functional T-type channels, potentially along with R-type channels, in these cardiac neurons. Fifty micromolar Ni2+, a concentration that suppresses currents in both T-type and R-type channels, blunted the PACAP-initiated increase in excitability. Ni2+ also blunted PACAP enhancement of the hyperpolarization-induced rebound depolarization and reversed the PACAP-mediated increase in excitability, after being initiated, in a subset of cells. Lastly, low voltage-activated currents, measured under perforated patch whole cell recording conditions and potentially flowing through T-type or R-type channels, were enhanced by PACAP. Together, our results suggest that a PACAP-enhanced, Ni2+-sensitive current contributes to PACAP-induced modulation of neuronal excitability. PMID:25810261

Voltage-dependent neuromodulation of Na+ channels by D1-like dopamine receptors in rat hippocampal neurons.

PubMed

Cantrell, A R; Scheuer, T; Catterall, W A

1999-07-01

Activation of D1-like dopamine (DA) receptors reduces peak Na+ current in acutely isolated hippocampal neurons through phosphorylation of the alpha subunit of the Na+ channel by cAMP-dependent protein kinase (PKA). Here we report that neuromodulation of Na+ currents by DA receptors via PKA is voltage-dependent in the range of -110 to -70 mV and is also sensitive to concurrent activation of protein kinase C (PKC). Depolarization enhanced the ability of D1-like DA receptors to reduce peak Na+ currents via the PKA pathway. Similar voltage-dependent modulation was observed when PKA was activated directly with the membrane-permeant PKA activator DCl-cBIMPS (cBIMPS; 20 microM), indicating that the membrane potential dependence occurs downstream of PKA. PKA activation caused only a small (-2.9 mV) shift in the voltage dependence of steady-state inactivation and had no effect on slow inactivation or on the rates of entry into the fast or slow inactivated states, suggesting that another mechanism is responsible for coupling of membrane potential changes to PKA modulation. Activation of PKC with a low concentration of the membrane-permeant diacylglycerol analog oleylacetyl glycerol also potentiated modulation by SKF 81297 or cBIMPS, and these effects were most striking at hyperpolarized membrane potentials where PKA modulation was not stimulated by membrane depolarization. Thus, activation of D1-like DA receptors causes a strong reduction in Na+ current via the PKA pathway, but it is effective primarily when it is combined with depolarization or activation of PKC. The convergence of these three distinct signaling modalities on the Na+ channel provides an intriguing mechanism for integration of information from multiple signaling pathways in the hippocampus and CNS.

Airborne Lidar Measurements of Below-canopy Surface Water Height , Slope and Optical Properties in the Florida Everglades Shark River Slough

NASA Astrophysics Data System (ADS)

Dabney, P.; Harding, D. J.; Valett, S. R.; Yu, A. W.; Feliciano, E. A.; Neuenschwander, A. L.; Pitts, K.

2015-12-01

Determining the presence, persistence, optical properties and variation in height and slope of surface water beneath the dense canopies of flooded forests and mangrove stands could contribute to studies of the acquisition of water and nutrients by plant roots. NASA's airborne Slope Imaging Multi-polarization Photon-counting Lidar (SIMPL) provides unique capabilities that can identify below-canopy surface water, measure its height with respect to vegetation constituents with sub-decimeter precision and quantify its slope. It also provides information on canopy structure and closure, the water column extinction profile as a proxy for turbidity and water depth, with the penetration depth constrained by turbidity. It achieves this by using four laser beams operating at two wavelengths with measurements of water surface elevation at 1064 nm (near infrared) and water column properties at 532 nm (green), analogous to a bathymetric lidar. Importantly the instrument adds a polarimetry function, like some atmospheric lidars, which measures the amount of depolarization determined by the degree to which the plane-parallel transmitted laser pulse energy is converted to the perpendicular state. The degree of depolarization is sensitive to the number of photon multiple-scattering events. For the water surface, which is specular consisting only of single-scattering events, the near-infrared received signal retains the parallel polarization state. Absence of the perpendicular signal uniquely identifies surface water. Penetration of green light and the depth profile of photons converted to the perpendicular state compared to those in the parallel state is a measure of water-column multiple scattering, providing a relative measure of turbidity. The amount of photons reflected from the canopy versus the water provides a wavelength-dependent measure of canopy closure. By rapidly firing laser pulses (11,400 pulses per second) with a narrow width (1 nsec) and detecting single photons with 8 cm ranging precision, the surface altimetry data is acquired with very high spatial and vertical resolution. Examples of these capabilities will be shown using data collected in 2011 along and across the flow axis of the Florida Everglades Shark River Slough, targeting the slough's Long Term Ecology Research (LTER) field sites.

The activation of calcium and calcium-activated potassium channels in mammalian colonic smooth muscle by substance P.

PubMed Central

Mayer, E A; Loo, D D; Snape, W J; Sachs, G

1990-01-01

1. The regulation of Ca2(+)-activated K+ channels by the agonist substance P in freshly dissociated smooth muscle cells from the rabbit longitudinal colonic muscle was characterized using the patch clamp technique. 2. In the cell-attached recording mode, when pipette and bath solutions contained equal [K+] (126 mM), the Ca2(+)-activated K+ channels showed a linear current-voltage relationship (between -50 mV and 50 mV) with a slope conductance of 210 +/- 35 pS (n = 12). Reversal potential measurements indicated that the channel was highly selective for K+ over Na+ (PK/PNa = 110). 3. Channels were activated by depolarizing membrane voltages and cytosolic Ca2+, and in inside-out patches channel activation depended sigmoidally on voltage and [Ca2+]. The potential for half-activation at a cytosolic [Ca2+] of 5 x 10(-6) M was 0 mV. A tenfold increase in cytosolic Ca2+ resulted in a 60 mV shift of the sigmoidal voltage activation curve to more negative potentials. 4. Threshold concentrations of substance P (10(-12) M), which did not result in cell contraction, caused a prolonged activation of K+ channels. The K+ channels were observed to open in clusters: simultaneous opening of multiple channels was interrupted by complete, prolonged channel closure. 5. Lowering bath [Ca2+] to submicromolar concentrations abolished the effect of substance P. The activation of K+ channels by substance P (10(-12) M) was also inhibited by the dihydropyridine nifedipine (10(-6) M), a blocker of L-type Ca2+ channels. 6. In the whole-cell recording mode, with the pipette solution containing 126 mM-KCl, 0.77 mM-EGTA and 1 mM-ATP, depolarization from a holding potential of -70 mV elicited outward currents which increased to steady-state values. These were K+ currents as they were blocked by TEA (tetraethylammonium, 30 mM) and Ba2+ (1 mM) and were abolished when pipette K+ was replaced by Cs+. 7. The depolarization-activated outward current was not affected by lowering extracellular [Ca2+] or by the Ca2+ channel antagonists Cd2+ (200 microM), nifedipine (10(-6)-10(-5) M) or verapamil (10(-6) M). The current was greatly reduced when the EGTA concentration in the pipette solution was increased from 0.77 to 10 mM. 8. When the pipette solution contained CsCl, membrane depolarization activated inward currents. The peak inward current was identified as current through L-type Ca2+ channels based on its voltage- and time-dependent kinetics, and its modulation by dihydropyridines.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:1691293

Utilizing a Water-Soluble Cryptophane with Fast Xenon Exchange Rates for Picomolar Sensitivity NMR Measurements

PubMed Central

Bai, Yubin; Hill, P. Aru; Dmochowski, Ivan J.

2012-01-01

Hyperpolarized 129Xe chemical exchange saturation transfer (129Xe Hyper-CEST) NMR is a powerful technique for the ultrasensitive, indirect detection of Xe host molecules (e.g., cryptophane-A). Irradiation at the appropriate Xe-cryptophane resonant radio frequency results in relaxation of the bound hyperpolarized 129Xe and rapid accumulation of depolarized 129Xe in bulk solution. The cryptophane effectively ‘catalyzes’ this process by providing a unique molecular environment for spin depolarization to occur, while allowing xenon exchange with the bulk solution during the hyperpolarized lifetime (T1 ≈ 1 min). Following this scheme, a triacetic acid cryptophane-A derivative (TAAC) was indirectly detected at 1.4 picomolar concentration at 320 K in aqueous solution, which is the record for a single-unit xenon host. To investigate this sensitivity enhancement, the xenon binding kinetics of TAAC in water was studied by NMR exchange lifetime measurement. At 297 K, kon ≈ 1.5 × 106 M−1s−1 and koff = 45 s−1, which represent the fastest Xe association and dissociation rates measured for a high-affinity, water-soluble xenon host molecule near rt. NMR linewidth measurements provided similar exchange rates at rt, which we assign to solvent-Xe exchange in TAAC. At 320 K, koff was estimated to be 1.1 × 103 s−1. In Hyper-CEST NMR experiments, the rate of 129Xe depolarization achieved by 14 pM TAAC in the presence of RF pulses was calculated to be 0.17 µM·s−1. On a per cryptophane basis, this equates to 1.2 × 104 129Xe atoms s−1 (or 4.6 × 104 Xe atoms s−1, all Xe isotopes), which is more than an order of magnitude faster than koff, the directly measurable Xe-TAAC exchange rate. This compels us to consider multiple Xe exchange processes for cryptophane-mediated bulk 129Xe depolarization, which provide at least 107-fold sensitivity enhancements over directly detected hyperpolarized 129Xe NMR signals. PMID:23106513

Myogenic Maturation by Optical-Training in Cultured Skeletal Muscle Cells.

PubMed

Asano, Toshifumi; Ishizuka, Toru; Yawo, Hiromu

2017-01-01

Optogenetic techniques are powerful tools for manipulating biological processes in identified cells using light under high temporal and spatial resolutions. Here, we describe an optogenetic training strategy to promote morphological maturation and functional development of skeletal muscle cells in vitro. Optical stimulation with a rhythmical frequency facilitates specific structural alignment of sarcomeric proteins. Optical stimulation also depolarizes the membrane potential, and induces contractile responses in synchrony with the given pattern of light pulses. These results suggest that optogenetic techniques can be employed to manipulate activity-dependent processes during myogenic development and control contraction of photosensitive skeletal muscle cells with high temporal and special precision.

The effects of magnetic fields on carnauba wax electret formation

NASA Astrophysics Data System (ADS)

Clator, Irvin G.

1987-08-01

The results of thermally stimulated depolarization current and effective surface charge-density measurements indicate that magnetic fields do not produce carnauba wax electrets and that previously reported data can be attributed to nonmagnetic effects.

Femtosecond laser pulse modification of amorphous silicon films: control of surface anisotropy

NASA Astrophysics Data System (ADS)

Shuleiko, D. V.; Potemkin, F. V.; Romanov, I. A.; Parhomenko, I. N.; Pavlikov, A. V.; Presnov, D. E.; Zabotnov, S. V.; Kazanskii, A. G.; Kashkarov, P. K.

2018-05-01

A one-dimensional surface relief with a 1.20  ±  0.02 µm period was formed in amorphous hydrogenated silicon films as a result of irradiation by femtosecond laser pulses (1.25 µm) with a fluence of 0.15 J cm‑2. Orientation of the formed structures was determined by the polarization vector of the radiation and the number of acting pulses. Nanocrystalline silicon phases with volume fractions from 40 to 67% were detected in the irradiated films according to the analysis of Raman spectra. Observed micro- and nanostructuring processes were caused by surface plasmon–polariton excitation and near-surface region nanocrystallization, respectively, in the high-intensity femtosecond laser field. Furthermore, the formation of Si-III and Si-XII silicon polymorphous modifications was observed after laser treatment with a large exposure dose. The conductivity of the film increased by three orders of magnitude at proper conditions after femtosecond laser nanocrystallization compared to the conductivity of the untreated amorphous surface. The conductivity anisotropy of the irradiated regions was also observed due to the depolarizing contribution of the surface structure, and the non-uniform intensity distribution in the cross-section of the laser beam used for modification.

Modulation of subthalamic T-type Ca2+ channels remedies locomotor deficits in a rat model of Parkinson disease

PubMed Central

Tai, Chun-Hwei; Yang, Ya-Chin; Pan, Ming-Kai; Huang, Chen-Syuan; Kuo, Chung-Chin

2011-01-01

An increase in neuronal burst activities in the subthalamic nucleus (STN) is a well-documented electrophysiological feature of Parkinson disease (PD). However, the causal relationship between subthalamic bursts and PD symptoms and the ionic mechanisms underlying the bursts remain to be established. Here, we have shown that T-type Ca2+ channels are necessary for subthalamic burst firing and that pharmacological blockade of T-type Ca2+ channels reduces motor deficits in a rat model of PD. Ni2+, mibefradil, NNC 55-0396, and efonidipine, which inhibited T-type Ca2+ currents in acutely dissociated STN neurons, but not Cd2+ and nifedipine, which preferentially inhibited L-type or the other non–T-type Ca2+ currents, effectively diminished burst activity in STN slices. Topical administration of inhibitors of T-type Ca2+ channels decreased in vivo STN burst activity and dramatically reduced the locomotor deficits in a rat model of PD. Cd2+ and nifedipine showed no such electrophysiological and behavioral effects. While low-frequency deep brain stimulation (DBS) has been considered ineffective in PD, we found that lengthening the duration of the low-frequency depolarizing pulse effectively improved behavioral measures of locomotion in the rat model of PD, presumably by decreasing the availability of T-type Ca2+ channels. We therefore conclude that modulation of subthalamic T-type Ca2+ currents and consequent burst discharges may provide new strategies for the treatment of PD. PMID:21737877

Quantitative evaluation of the neuroprotective effects of thiopental sodium, propofol, and halothane on brain ischemia in the gerbil: effects of the anesthetics on ischemic depolarization and extracellular glutamate concentration.

PubMed

Kobayashi, Motomu; Takeda, Yoshimasa; Taninishi, Hideki; Takata, Ken; Aoe, Hisami; Morita, Kiyoshi

2007-07-01

Although propofol and thiopental are commonly used as neuroprotective agents, it has not been determined which is more neuroprotective. This study was designed to quantitatively evaluate the neuroprotective effects of thiopental, propofol, and halothane on brain ischemia by determining P50, ischemic time necessary for causing 50% neuronal damage. Gerbils were anesthetized with thiopental, propofol, or halothane and underwent 2-vessel occlusion (0, 3, 5 or 10 min). Direct current potentials were measured in bilateral CA1 regions, in which histologic evaluation was performed 5 days later. In some animals, extracellular glutamate concentrations (microdialysis) were measured during 7.5 minutes of ischemia. P50 in the thiopental, propofol, and halothane groups were estimated to be 8.4, 6.5 (P<0.05, vs. thiopental), and 5.1 (P<0.05) minutes, respectively. Durations of ischemic depolarization were equally reduced in the thiopental and propofol groups compared with that in the halothane group. Severity of neuronal damage with identical duration of ischemic depolarization was attenuated by thiopental compared with the effect of propofol. Maximum glutamate concentrations in the thiopental and propofol group were significantly reduced compared with that in the halothane groups but were comparable. By using P50, we found that the neuroprotective effect of thiopental was greater than that of propofol. Although duration of ischemic depolarization was equally reduced in thiopental and propofol groups, thiopental has a greater suppressive effect on neuronal injury during identical duration of ischemic depolarization than propofol does. Glutamate concentration during brain ischemia tended to be attenuated more by thiopental than by propofol, but it was not statistically significant.

Rapid kill of malaria parasites by artemisinin and semi-synthetic endoperoxides involves ROS-dependent depolarization of the membrane potential

PubMed Central

Antoine, Thomas; Fisher, Nicholas; Amewu, Richard; O'Neill, Paul M.; Ward, Stephen A.; Biagini, Giancarlo A.

2014-01-01

Objectives Artemisinin and artemisinin semi-synthetic derivatives (collectively known as endoperoxides) are first-line antimalarials for the treatment of uncomplicated and severe malaria. Endoperoxides display very fast killing rates and are generally recalcitrant to parasite resistance development. These key pharmacodynamic features are a result of a complex mechanism of action, the details of which lack consensus. Here, we report on the primary physiological events leading to parasite death. Methods Parasite mitochondrial (ΔΨm) and plasma membrane (ΔΨp) electrochemical potentials were measured using real-time single-cell imaging following exposure to pharmacologically relevant concentrations of endoperoxides (artemisinin, dihydroartemisinin, artesunate and the synthetic tetraoxane RKA182). In addition, mitochondrial electron transport chain components NADH:quinone oxidoreductase (alternative complex I), bc1 (complex III) and cytochrome oxidase (complex IV) were investigated to determine their functional sensitivity to the various endoperoxides. Results Parasite exposure to endoperoxides resulted in rapid depolarization of parasite ΔΨm and ΔΨp. The rate of depolarization was decreased in the presence of a reactive oxygen species (ROS) scavenger and Fe3+ chelators. Depolarization of ΔΨm by endoperoxides is not believed to be through the inhibition of mitochondrial electron transport chain components, owing to the lack of significant inhibition when assayed directly. Conclusions The depolarization of ΔΨm and ΔΨp is shown to be mediated via the generation of ROS that are initiated by iron bioactivation of endoperoxides and/or catalysed by iron-dependent oxidative stress. These data are discussed in the context of current hypotheses concerning the mode of action of endoperoxides. PMID:24335485

Differences in receptor-evoked membrane electrical responses in native and mRNA-injected Xenopus oocytes.

PubMed

Oron, Y; Gillo, B; Gershengorn, M C

1988-06-01

Xenopus laevis oocytes are giant cells suitable for studies of plasma membrane receptors and signal transduction pathways because of their capacity to express receptors after injection of heterologous mRNA. We studied depolarizing chloride currents evoked by acetylcholine (AcCho) in native oocytes ("intrinsic AcCho response"), by thyrotropin-releasing hormone (TRH) in oocytes injected with pituitary (GH3) cell RNA ("acquired TRH response"), and by AcCho in oocytes injected with rat brain RNA ("acquired AcCho response"). We found differences in the latencies and patterns of these responses and in the responsiveness to these agonists when applied to the animal or vegetal hemisphere, even though all of the responses are mediated by the same signal transduction pathway. The common intrinsic response to AcCho is characterized by minimal latency (0.86 +/- 0.05 sec), a rapid, transient depolarization followed by a distinct prolonged depolarization, and larger responses obtained after AcCho application at the vegetal rather than the animal hemisphere. By contrast, the acquired responses to TRH and AcCho are characterized by much longer latencies, 9.3 +/- 1.0 and 5.5 +/- 0.8 sec, respectively, and large rapid depolarizations followed by less distinct prolonged depolarizations. The responsiveness on the two hemispheres to TRH and AcCho in mRNA-injected oocytes is opposite to that for the common intrinsic AcCho response in that there is a much greater response when agonist is applied at the animal rather than the vegetal hemisphere. We suggest that the differences in these responses are caused by differences in the intrinsic properties of these receptors. Because different receptors appear to be segregated in the same oocyte in distinct localizations, Xenopus oocytes may be an important model system in which to study receptor sorting in polarized cells.

Cellular basis for singing motor pattern generation in the field cricket (Gryllus bimaculatus DeGeer)

PubMed Central

Schöneich, Stefan; Hedwig, Berthold

2012-01-01

The singing behavior of male crickets allows analyzing a central pattern generator (CPG) that was shaped by sexual selection for reliable production of species-specific communication signals. After localizing the essential ganglia for singing in Gryllus bimaculatus, we now studied the calling song CPG at the cellular level. Fictive singing was initiated by pharmacological brain stimulation. The motor pattern underlying syllables and chirps was recorded as alternating spike bursts of wing-opener and wing-closer motoneurons in a truncated wing nerve; it precisely reflected the natural calling song. During fictive singing, we intracellularly recorded and stained interneurons in thoracic and abdominal ganglia and tested their impact on the song pattern by intracellular current injections. We identified three interneurons of the metathoracic and first unfused abdominal ganglion that rhythmically de- and hyperpolarized in phase with the syllable pattern and spiked strictly before the wing-opener motoneurons. Depolarizing current injection in two of these opener interneurons caused additional rhythmic singing activity, which reliably reset the ongoing chirp rhythm. The closely intermeshing arborizations of the singing interneurons revealed the dorsal midline neuropiles of the metathoracic and three most anterior abdominal neuromeres as the anatomical location of singing pattern generation. In the same neuropiles, we also recorded several closer interneurons that rhythmically hyper- and depolarized in the syllable rhythm and spiked strictly before the wing-closer motoneurons. Some of them received pronounced inhibition at the beginning of each chirp. Hyperpolarizing current injection in the dendrite revealed postinhibitory rebound depolarization as one functional mechanism of central pattern generation in singing crickets. PMID:23170234

Membrane depolarization inhibits spiral ganglion neurite growth via activation of multiple types of voltage sensitive calcium channels and calpain

PubMed Central

Roehm, Pamela C.; Xu, Ningyong; Woodson, Erika A.; Green, Steven H.; Hansen, Marlan R.

2008-01-01

The effect of membrane electrical activity on spiral ganglion neuron (SGN) neurite growth remains unknown despite its relevance to cochlear implant technology. We demonstrate that membrane depolarization delays the initial formation and inhibits the subsequent extension of cultured SGN neurites. This inhibition depends directly on the level of depolarization with higher levels of depolarization causing retraction of existing neurites. Cultured SGNs express subunits for L-type, N-type, and P/Q type voltage-gated calcium channels (VGCCs) and removal of extracellular Ca2+ or treatment with a combination of L-type, N-type, P/Q-type VGCC antagonists rescues SGN neurite growth under depolarizing conditions. By measuring the fluorescence intensity of SGNs loaded with the fluorogenic calpain substrate t-butoxy carbonyl-Leu-Met-chloromethylaminocoumarin (20 μM), we demonstrate that depolarization activates calpains. Calpeptin (15 μM), a calpain inhibitor, prevents calpain activation by depolarization and rescues neurite growth in depolarized SGNs suggesting that calpain activation contributes to the inhibition of neurite growth by depolarization. PMID:18055215

Dynamics of valley pseudospin in single-layer WSe2. Inter-valley scattering mediated by electron-phonon interaction

NASA Astrophysics Data System (ADS)

Molina-Sanchez, Alejandro; Sangalli, Davide; Wirtz, Ludger; Marini, Andrea

In a time-dependent Kerr experiment a circularly polarized laser field is used to selectively populate the K+/- electronic valleys of single-layer WSe2. This carrier population corresponds to a finite pseudospin polarization that dictates the valleytronic properties of WSe2, but whose decay mechanism still remains largely debated. Time-dependent Kerr experiments provide an accurate way to visualize the pseudospin dynamics by measuring the rotation of a linearly polarized probe pulse applied after a circularly polarized and short pump pulse. We present here a clear, accurate and parameter-free description of the valley pseudospin dynamics in single-layer WSe2. By using an ab-initio approach we solve unambiguously the long standing debate about the dominant mechanism that drives the valley depolarization. Our results are in excellent agreement with recent time-dependent Kerr experiments. The decay dynamics and peculiar temperature dependence is explained in terms of electron phonon mediated processes that induce spin-flip inter-valley transitions.

Functional ion channels in human pulmonary artery smooth muscle cells: Voltage-dependent cation channels

PubMed Central

Firth, Amy L.; Remillard, Carmelle V.; Platoshyn, Oleksandr; Fantozzi, Ivana; Ko, Eun A.; Yuan, Jason X.-J.

2011-01-01

The activity of voltage-gated ion channels is critical for the maintenance of cellular membrane potential and generation of action potentials. In turn, membrane potential regulates cellular ion homeostasis, triggering the opening and closing of ion channels in the plasma membrane and, thus, enabling ion transport across the membrane. Such transmembrane ion fluxes are important for excitation–contraction coupling in pulmonary artery smooth muscle cells (PASMC). Families of voltage-dependent cation channels known to be present in PASMC include voltage-gated K+ (Kv) channels, voltage-dependent Ca2+-activated K+ (Kca) channels, L- and T- type voltage-dependent Ca2+ channels, voltage-gated Na+ channels and voltage-gated proton channels. When cells are dialyzed with Ca2+-free K+- solutions, depolarization elicits four components of 4-aminopyridine (4-AP)-sensitive Kvcurrents based on the kinetics of current activation and inactivation. In cell-attached membrane patches, depolarization elicits a wide range of single-channel K+ currents, with conductances ranging between 6 and 290 pS. Macroscopic 4-AP-sensitive Kv currents and iberiotoxin-sensitive Kca currents are also observed. Transcripts of (a) two Na+ channel α-subunit genes (SCN5A and SCN6A), (b) six Ca2+ channel α–subunit genes (α1A, α1B, α1X, α1D, α1Eand α1G) and many regulatory subunits (α2δ1, β1-4, and γ6), (c) 22 Kv channel α–subunit genes (Kv1.1 - Kv1.7, Kv1.10, Kv2.1, Kv3.1, Kv3.3, Kv3.4, Kv4.1, Kv4.2, Kv5.1, Kv 6.1-Kv6.3, Kv9.1, Kv9.3, Kv10.1 and Kv11.1) and three Kv channel β-subunit genes (Kvβ1-3) and (d) four Kca channel α–subunit genes (Sloα1 and SK2-SK4) and four Kca channel β-subunit genes (Kcaβ1-4) have been detected in PASMC. Tetrodotoxin-sensitive and rapidly inactivating Na+ currents have been recorded with properties similar to those in cardiac myocytes. In the presence of 20 mM external Ca2+, membrane depolarization from a holding potential of -100 mV elicits a rapidly inactivating T-type Ca2+ current, while depolarization from a holding potential of -70 mV elicits a slowly inactivating dihydropyridine-sensitive L-type Ca2+ current. This review will focus on describing the electrophysiological properties and molecular identities of these voltage-dependent cation channels in PASMC and their contribution to the regulation of pulmonary vascular function and its potential role in the pathogenesis of pulmonary vascular disease. PMID:21927714

Depolarized FRET (depolFRET) on the cell surface: FRET control by photoselection.

PubMed

Bene, László; Gogolák, Péter; Ungvári, Tamás; Bagdány, Miklós; Nagy, István; Damjanovich, László

2016-02-01

Sensitivity of FRET in hetero- and homo-FRET systems on the photoselected orientation distribution of donors has been proven by using polarized and depolarized light for excitation. FRET as well as donor and acceptor anisotropies have been simultaneously measured in a dual emission-polarization scheme realized in a conventional flow cytometer by using single laser excitation and applying fluorophore-conjugated mAbs against the MHCI and MHCII cell surface receptors. Depolarization of the originally polarized light have been achieved by using crystal depolarizers based on Cornu's principle, a quarter-wave plate for circular polarization, and a parallel beam splitter acting as a diagonal-polarizer for dual-polarization excitation. Simultaneous analysis of intensity-based FRET efficiency and acceptor depolarization equivocally report that depolarization of light may increase FRET in an amount depending on the acceptor-to-donor concentration ratio. Acceptor depolarization turned to be more sensitive to FRET than donor hyper-polarization and even than intensity-based FRET efficiency. It can be used as a sensitive tool for monitoring changes in the dynamics of the donor-acceptor pairs. The basic observations of FRET enhancement and increased acceptor depolarization obtained for hetero-FRET are paralleled by analog observations of homo-FRET enhancements under depolarized excitation. In terms of the orientation factor for FRET, the FRET enhancements on depolarization in the condition of the macroscopically isotropic orientation distributions such as those of the cell surface bound fluorophores report on the presence of local orientation mismatches of the donor and acceptor preventing the optimal FRET in the polarized case, which may be eliminated by the excitation depolarization. A theory of fluorescence anisotropy for depolarized excitation is also presented. Copyright © 2015 Elsevier B.V. All rights reserved.

The mechanism of excitation by acetylcholine in the cerebral cortex

PubMed Central

Krnjević, K.; Pumain, R.; Renaud, L.

1971-01-01

1. The muscarinic depolarizing action of ACh on cortical neurones is associated with an increase in membrane resistance (mean ΔV/ΔR = 3·16 mV/MΩ). 2. ACh also promotes repetitive firing by slowing repolarization after spikes. 3. The depolarizing effect has a mean reversal level of -86·7 mV (with mean resting potential -56 mV). 4. It is concluded that as a muscarinic excitatory agent, ACh probably acts by reducing the resting K+ conductance of cortical neurones, and also the delayed K+ current of the action potential. 5. These results are discussed in relation to the possible role of ACh in cortical function. PMID:5579661

Blockade of HERG human K+ channels and IKr of guinea-pig cardiomyocytes by the antipsychotic drug clozapine.

PubMed

Lee, So-Young; Kim, Young-Jin; Kim, Kyong-Tai; Choe, Han; Jo, Su-Hyun

2006-06-01

Clozapine, a commonly used antipsychotic drug, can induce QT prolongation, which may lead to torsades de pointes and sudden death. To investigate the arrhythmogenic side effects of clozapine, we studied the impact of clozapine on human ether-a-go-go-related gene (HERG) channels expressed in Xenopus oocytes and HEK293 cells, and on the delayed rectifier K(+) currents of guinea-pig cardiomyocytes. Clozapine dose-dependently decreased the amplitudes of the currents at the end of voltage steps, and the tail currents of HERG. The IC(50) for the clozapine blockade of HERG currents in Xenopus oocytes progressively decreased relative to depolarization (39.9 microM at -40 mV, 28.3 microM at 0 mV and 22.9 microM at +40 mV), whereas the IC(50) for the clozapine-induced blockade of HERG currents in HEK293 cells at 36 degrees C was 2.5 microM at +20 mV. The clozapine-induced blockade of HERG currents was time dependent: the fractional current was 0.903 of the control at the beginning of the pulse, but declined to 0.412 after 4 s at a test potential of 0 mV. The clozapine-induced blockade of HERG currents was use-dependent, exhibiting more rapid onset and greater steady state blockade at higher frequencies of activation, with a partial relief of blockade observed when the frequency of activation was decreased. In guinea-pig ventricular myocytes held at 36 degrees C, treatment with 1 and 5 microM clozapine blocked the rapidly activating delayed rectifier K(+) current (I(Kr)) by 24.7 and 79.6%, respectively, but did not significantly block the slowly activating delayed rectifier K(+) current (I(Ks)). Our findings collectively suggest that blockade of HERG currents and I(Kr), but not I(Ks), may contribute to the arrhythmogenic side effects of clozapine.

Blockade of HERG human K+ channels and IKr of guinea-pig cardiomyocytes by the antipsychotic drug clozapine

PubMed Central

Lee, So-Young; Kim, Young-Jin; Kim, Kyong-Tai; Choe, Han; Jo, Su-Hyun

2006-01-01

Clozapine, a commonly used antipsychotic drug, can induce QT prolongation, which may lead to torsades de pointes and sudden death. To investigate the arrhythmogenic side effects of clozapine, we studied the impact of clozapine on human ether-a-go-go-related gene (HERG) channels expressed in Xenopus oocytes and HEK293 cells, and on the delayed rectifier K+ currents of guinea-pig cardiomyocytes. Clozapine dose-dependently decreased the amplitudes of the currents at the end of voltage steps, and the tail currents of HERG. The IC50 for the clozapine blockade of HERG currents in Xenopus oocytes progressively decreased relative to depolarization (39.9 μM at −40 mV, 28.3 μM at 0 mV and 22.9 μM at +40 mV), whereas the IC50 for the clozapine-induced blockade of HERG currents in HEK293 cells at 36°C was 2.5 μM at +20 mV. The clozapine-induced blockade of HERG currents was time dependent: the fractional current was 0.903 of the control at the beginning of the pulse, but declined to 0.412 after 4 s at a test potential of 0 mV. The clozapine-induced blockade of HERG currents was use-dependent, exhibiting more rapid onset and greater steady state blockade at higher frequencies of activation, with a partial relief of blockade observed when the frequency of activation was decreased. In guinea-pig ventricular myocytes held at 36°C, treatment with 1 and 5 μM clozapine blocked the rapidly activating delayed rectifier K+ current (IKr) by 24.7 and 79.6%, respectively, but did not significantly block the slowly activating delayed rectifier K+ current (IKs). Our findings collectively suggest that blockade of HERG currents and IKr, but not IKs, may contribute to the arrhythmogenic side effects of clozapine. PMID:16633353

Electroporation followed by electrochemical measurement of quantal transmitter release from single cells using a patterned microelectrode.

PubMed

Ghosh, Jaya; Liu, Xin; Gillis, Kevin D

2013-06-07

An electrochemical microelectrode located immediately adjacent to a single neuroendocrine cell can record spikes of amperometric current that result from exocytosis of oxidizable transmitter from individual vesicles, i.e., quantal exocytosis. Here, we report the development of an efficient method where the same electrochemical microelectrode is used to electropermeabilize an adjacent chromaffin cell and then measure the consequent quantal catecholamine release using amperometry. Trains of voltage pulses, 5-7 V in amplitude and 0.1-0.2 ms in duration, were used to reliably trigger release from cells using gold electrodes. Amperometric spikes induced by electropermeabilization had similar areas, peak heights and durations as amperometric spikes elicited by depolarizing high K(+) solutions, therefore release occurs from individual secretory granules. Uptake of trypan blue stain into cells demonstrated that the plasma membrane is permeabilized by the voltage stimulus. Voltage pulses did not degrade the electrochemical sensitivity of the electrodes assayed using a test analyte. Surprisingly, robust quantal release was elicited upon electroporation in the absence of Ca(2+) in the bath solution (0 Ca(2+)/5 mM EGTA). In contrast, electropermeabilization-induced transmitter release required Cl(-) in the bath solution in that bracketed experiments demonstrated a steep dependence of the rate of electropermeabilization-induced transmitter release on [Cl(-)] between 2 and 32 mM. Using the same electrochemical electrode to electroporate and record quantal release of catecholamines from an individual chromaffin cell allows precise timing of the stimulus, stimulation of a single cell at a time, and can be used to load membrane-impermeant substances into a cell.

Stitching Type Large Aperture Depolarizer for Gas Monitoring Imaging Spectrometer

NASA Astrophysics Data System (ADS)

Liu, X.; Li, M.; An, N.; Zhang, T.; Cao, G.; Cheng, S.

2018-04-01

To increase the accuracy of radiation measurement for gas monitoring imaging spectrometer, it is necessary to achieve high levels of depolarization of the incoming beam. The preferred method in space instrument is to introduce the depolarizer into the optical system. It is a combination device of birefringence crystal wedges. Limited to the actual diameter of the crystal, the traditional depolarizer cannot be used in the large aperture imaging spectrometer (greater than 100 mm). In this paper, a stitching type depolarizer is presented. The design theory and numerical calculation model for dual babinet depolarizer were built. As required radiometric accuracies of the imaging spectrometer with 250 mm × 46 mm aperture, a stitching type dual babinet depolarizer was design in detail. Based on designing the optimum structural parmeters the tolerance of wedge angle refractive index, and central thickness were given. The analysis results show that the maximum residual polarization degree of output light from depolarizer is less than 2 %. The design requirements of polarization sensitivity is satisfied.

Polarization changes at Lyot depolarizer output for different types of input beams.

PubMed

de Sande, J Carlos G; Piquero, Gemma; Teijeiro, Cristina

2012-03-01

Lyot depolarizers are optical devices made of birefringent materials used for producing unpolarized beams from totally polarized incident light. The depolarization is produced for polychromatic input beams due to the different phase introduced by the Lyot depolarizer for each wavelength. The effect of this device on other types of incident fields is investigated. In particular two cases are analyzed: (i) monochromatic and nonuniformly polarized incident beams and (ii) incident light synthesized by superposition of two monochromatic orthogonally polarized beams with different wavelengths. In the last case, it is theoretically and experimentally shown that the Lyot depolarizer increases the degree of polarization instead of depolarizes.

Modulation of CaV2.1 channels by neuronal calcium sensor-1 induces short-term synaptic facilitation.

PubMed

Yan, Jin; Leal, Karina; Magupalli, Venkat G; Nanou, Evanthia; Martinez, Gilbert Q; Scheuer, Todd; Catterall, William A

2014-11-01

Facilitation and inactivation of P/Q-type Ca2+ currents mediated by Ca2+/calmodulin binding to Ca(V)2.1 channels contribute to facilitation and rapid depression of synaptic transmission, respectively. Other calcium sensor proteins displace calmodulin from its binding site and differentially modulate P/Q-type Ca2 + currents, resulting in diverse patterns of short-term synaptic plasticity. Neuronal calcium sensor-1 (NCS-1, frequenin) has been shown to enhance synaptic facilitation, but the underlying mechanism is unclear. We report here that NCS-1 directly interacts with IQ-like motif and calmodulin-binding domain in the C-terminal domain of Ca(V)2.1 channel. NCS-1 reduces Ca2 +-dependent inactivation of P/Q-type Ca2+ current through interaction with the IQ-like motif and calmodulin-binding domain without affecting peak current or activation kinetics. Expression of NCS-1 in presynaptic superior cervical ganglion neurons has no effect on synaptic transmission, eliminating effects of this calcium sensor protein on endogenous N-type Ca2+ currents and the endogenous neurotransmitter release machinery. However, in superior cervical ganglion neurons expressing wild-type Ca(V)2.1 channels, co-expression of NCS-1 induces facilitation of synaptic transmission in response to paired pulses and trains of depolarizing stimuli, and this effect is lost in Ca(V)2.1 channels with mutations in the IQ-like motif and calmodulin-binding domain. These results reveal that NCS-1 directly modulates Ca(V)2.1 channels to induce short-term synaptic facilitation and further demonstrate that CaS proteins are crucial in fine-tuning short-term synaptic plasticity.

For the depolarization of linearly polarized light by smoke particles

NASA Astrophysics Data System (ADS)

Sun, Wenbo; Liu, Zhaoyan; Videen, Gorden; Fu, Qiang; Muinonen, Karri; Winker, David M.; Lukashin, Constantine; Jin, Zhonghai; Lin, Bing; Huang, Jianping

2013-06-01

The CALIPSO satellite mission consistently measures volume (including molecule and particulate) light depolarization ratio of ∼2% for smoke, compared to ∼1% for marine aerosols and ∼15% for dust. The observed ∼2% smoke depolarization ratio comes primarily from the nonspherical habits of particles in the smoke at certain particle sizes. In this study, the depolarization of linearly polarized light by small sphere aggregates and irregular Gaussian-shaped particles is studied, to reveal the physics between the depolarization of linearly polarized light and smoke aerosol shape and size. It is found that the depolarization ratio curves of Gaussian-deformed spheres are very similar to sphere aggregates in terms of scattering-angle dependence and particle size parameters when particle size parameter is smaller than 1.0π. This demonstrates that small randomly oriented nonspherical particles have some common depolarization properties as functions of scattering angle and size parameter. This may be very useful information for characterization and active remote sensing of smoke particles using polarized light. We also show that the depolarization ratio from the CALIPSO measurements could be used to derive smoke aerosol particle size. From the calculation results for light depolarization ratio by Gaussian-shaped smoke particles and the CALIPSO-measured light depolarization ratio of ∼2% for smoke, the mean particle size of South-African smoke is estimated to be about half of the 532nm wavelength of the CALIPSO lidar.

Depolarizing Actions of Hydrogen Sulfide on Hypothalamic Paraventricular Nucleus Neurons

PubMed Central

Khademullah, C. Sahara; Ferguson, Alastair V.

2013-01-01

Hydrogen sulfide (H2S) is a novel neurotransmitter that has been shown to influence cardiovascular functions as well and corticotrophin hormone (CRH) secretion. Since the paraventricular nucleus of the hypothalamus (PVN) is a central relay center for autonomic and endocrine functions, we sought to investigate the effects of H2S on the neuronal population of the PVN. Whole cell current clamp recordings were acquired from the PVN neurons and sodium hydrosulfide hydrate (NaHS) was bath applied at various concentrations (0.1, 1, 10, and 50 mM). NaHS (1, 10, and 50 mM) elicited a concentration-response relationship from the majority of recorded neurons, with almost exclusively depolarizing effects following administration. Cells responded and recovered from NaHS administration quickly and the effects were repeatable. Input differences from baseline and during the NaHS-induced depolarization uncovered a biphasic response, implicating both a potassium and non-selective cation conductance. The results from the neuronal population of the PVN shed light on the possible physiological role that H2S has in autonomic and endocrine function. PMID:23691233

Muscarinic Long-Term Enhancement of Tonic and Phasic GABAA Inhibition in Rat CA1 Pyramidal Neurons

PubMed Central

Domínguez, Soledad; Fernández de Sevilla, David; Buño, Washington

2016-01-01

Acetylcholine (ACh) regulates network operation in the hippocampus by controlling excitation and inhibition in rat CA1 pyramidal neurons (PCs), the latter through gamma-aminobutyric acid type-A receptors (GABAARs). Although, the enhancing effects of ACh on GABAARs have been reported (Dominguez et al., 2014, 2015), its role in regulating tonic GABAA inhibition has not been explored in depth. Therefore, we aimed at determining the effects of the activation of ACh receptors on responses mediated by synaptic and extrasynaptic GABAARs. Here, we show that under blockade of ionotropic glutamate receptors ACh, acting through muscarinic type 1 receptors, paired with post-synaptic depolarization induced a long-term enhancement of tonic GABAA currents (tGABAA) and puff-evoked GABAA currents (pGABAA). ACh combined with depolarization also potentiated IPSCs (i.e., phasic inhibition) in the same PCs, without signs of interactions of synaptic responses with pGABAA and tGABAA, suggesting the contribution of two different GABAA receptor pools. The long-term enhancement of GABAA currents and IPSCs reduced the excitability of PCs, possibly regulating plasticity and learning in behaving animals. PMID:27833531

Pulse charging of lead-acid traction cells

NASA Technical Reports Server (NTRS)

Smithrick, J. J.

1980-01-01

Pulse charging, as a method of rapidly and efficiently charging 300 amp-hour lead-acid traction cells for an electric vehicle application was investigated. A wide range of charge pulse current square waveforms were investigated and the results were compared to constant current charging at the time averaged pulse current values. Representative pulse current waveforms were: (1) positive waveform-peak charge pulse current of 300 amperes (amps), discharge pulse-current of zero amps, and a duty cycle of about 50%; (2) Romanov waveform-peak charge pulse current of 300 amps, peak discharge pulse current of 15 amps, and a duty of 50%; and (3) McCulloch waveform peak charge pulse current of 193 amps, peak discharge pulse current of about 575 amps, and a duty cycle of 94%. Experimental results indicate that on the basis of amp-hour efficiency, pulse charging offered no significant advantage as a method of rapidly charging 300 amp-hour lead-acid traction cells when compared to constant current charging at the time average pulse current value. There were, however, some disadvantages of pulse charging in particular a decrease in charge amp-hour and energy efficiencies and an increase in cell electrolyte temperature. The constant current charge method resulted in the best energy efficiency with no significant sacrifice of charge time or amp-hour output. Whether or not pulse charging offers an advantage over constant current charging with regard to the cell charge/discharge cycle life is unknown at this time.

Effects of Pulse Parameters on Weld Microstructure and Mechanical Properties of Extra Pulse Current Aided Laser Welded 2219 Aluminum Alloy Joints.

PubMed

Zhang, Xinge; Li, Liqun; Chen, Yanbin; Yang, Zhaojun; Chen, Yanli; Guo, Xinjian

2017-09-15

In order to expand the application range of laser welding and improve weld quality, an extra pulse current was used to aid laser-welded 2219 aluminum alloy, and the effects of pulse current parameters on the weld microstructure and mechanical properties were investigated. The effect mechanisms of the pulse current interactions with the weld pool were evaluated. The results indicated that the coarse dendritic structure in the weld zone changed to a fine equiaxed structure using an extra pulse current, and the pulse parameters, including medium peak current, relatively high pulse frequency, and low pulse duty ratio benefited to improving the weld structure. The effect mechanisms of the pulse current were mainly ascribed to the magnetic pinch effect, thermal effect, and electromigration effect caused by the pulse current. The effect of the pulse parameters on the mechanical properties of welded joints were consistent with that of the weld microstructure. The tensile strength and elongation of the optimal pulse current-aided laser-welded joint increased by 16.4% and 105%, respectively, compared with autogenous laser welding.

Effects of Pulse Parameters on Weld Microstructure and Mechanical Properties of Extra Pulse Current Aided Laser Welded 2219 Aluminum Alloy Joints

PubMed Central

Zhang, Xinge; Li, Liqun; Chen, Yanbin; Yang, Zhaojun; Chen, Yanli; Guo, Xinjian

2017-01-01

In order to expand the application range of laser welding and improve weld quality, an extra pulse current was used to aid laser-welded 2219 aluminum alloy, and the effects of pulse current parameters on the weld microstructure and mechanical properties were investigated. The effect mechanisms of the pulse current interactions with the weld pool were evaluated. The results indicated that the coarse dendritic structure in the weld zone changed to a fine equiaxed structure using an extra pulse current, and the pulse parameters, including medium peak current, relatively high pulse frequency, and low pulse duty ratio benefited to improving the weld structure. The effect mechanisms of the pulse current were mainly ascribed to the magnetic pinch effect, thermal effect, and electromigration effect caused by the pulse current. The effect of the pulse parameters on the mechanical properties of welded joints were consistent with that of the weld microstructure. The tensile strength and elongation of the optimal pulse current-aided laser-welded joint increased by 16.4% and 105%, respectively, compared with autogenous laser welding. PMID:28914825

Heterogeneous incidence and propagation of spreading depolarizations

PubMed Central

Kaufmann, Dan; Theriot, Jeremy J; Zyuzin, Jekaterina; Service, C Austin; Chang, Joshua C; Tang, Y Tanye; Bogdanov, Vladimir B; Multon, Sylvie; Schoenen, Jean; Ju, Y Sungtaek

2016-01-01

Spreading depolarizations are implicated in a diverse set of neurologic diseases. They are unusual forms of nervous system activity in that they propagate very slowly and approximately concentrically, apparently not respecting the anatomic, synaptic, functional, or vascular architecture of the brain. However, there is evidence that spreading depolarizations are not truly concentric, isotropic, or homogeneous, either in space or in time. Here we present evidence from KCl-induced spreading depolarizations, in mouse and rat, in vivo and in vitro, showing the great variability that these depolarizations can exhibit. This variability can help inform the mechanistic understanding of spreading depolarizations, and it has implications for their phenomenology in neurologic disease. PMID:27562866

Pharmacological Conversion of a Cardiac Inward Rectifier into an Outward Rectifier Potassium Channel.

PubMed

Moreno-Galindo, Eloy G; Sanchez-Chapula, Jose A; Tristani-Firouzi, Martin; Navarro-Polanco, Ricardo A

2016-09-01

Potassium (K(+)) channels are crucial for determining the shape, duration, and frequency of action-potential firing in excitable cells. Broadly speaking, K(+) channels can be classified based on whether their macroscopic current outwardly or inwardly rectifies, whereby rectification refers to a change in conductance with voltage. Outwardly rectifying K(+) channels conduct greater current at depolarized membrane potentials, whereas inward rectifier channels conduct greater current at hyperpolarized membrane potentials. Under most circumstances, outward currents through inwardly rectifying K(+) channels are reduced at more depolarized potentials. However, the acetylcholine-gated K(+) channel (KACh) conducts current that inwardly rectifies when activated by some ligands (such as acetylcholine), and yet conducts current that outwardly rectifies when activated by other ligands (for example, pilocarpine and choline). The perplexing and paradoxical behavior of KACh channels is due to the intrinsic voltage sensitivity of the receptor that activates KACh channels, the M2 muscarinic receptor (M2R). Emerging evidence reveals that the affinity of M2R for distinct ligands varies in a voltage-dependent and ligand-specific manner. These intrinsic receptor properties determine whether current conducted by KACh channels inwardly or outwardly rectifies. This review summarizes the most recent concepts regarding the intrinsic voltage sensitivity of muscarinic receptors and the consequences of this intriguing behavior on cardiac physiology and pharmacology of KACh channels. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Ultrahigh energy density harvested from domain-engineered relaxor ferroelectric single crystals under high strain rate loading

NASA Astrophysics Data System (ADS)

Shkuratov, Sergey I.; Baird, Jason; Antipov, Vladimir G.; Talantsev, Evgueni F.; Chase, Jay B.; Hackenberger, Wesley; Luo, Jun; Jo, Hwan R.; Lynch, Christopher S.

2017-04-01

Relaxor ferroelectric single crystals have triggered revolution in electromechanical systems due to their superior piezoelectric properties. Here the results are reported on experimental studies of energy harvested from (1-y-x)Pb(In1/2Nb1/2)O3-(y)Pb(Mg1/3Nb2/3)O3-(x)PbTiO3 (PIN-PMN-PT) crystals under high strain rate loading. Precise control of ferroelectric properties through composition, size and crystallographic orientation of domains made it possible to identify single crystals that release up to three times more electric charge density than that produced by PbZr0.52Ti0.48O3 (PZT 52/48) and PbZr0.95Ti0.05O3 (PZT 95/5) ferroelectric ceramics under identical loading conditions. The obtained results indicate that PIN-PMN-PT crystals became completely depolarized under 3.9 GPa compression. It was found that the energy density generated in the crystals during depolarization in the high voltage mode is four times higher than that for PZT 52/48 and 95/5. The obtained results promise new single crystal applications in ultrahigh-power transducers that are capable of producing hundreds kilovolt pulses and gigawatt-peak power microwave radiation.

Ultrahigh energy density harvested from domain-engineered relaxor ferroelectric single crystals under high strain rate loading

PubMed Central

Shkuratov, Sergey I.; Baird, Jason; Antipov, Vladimir G.; Talantsev, Evgueni F.; Chase, Jay B.; Hackenberger, Wesley; Luo, Jun; Jo, Hwan R.; Lynch, Christopher S.

2017-01-01

Relaxor ferroelectric single crystals have triggered revolution in electromechanical systems due to their superior piezoelectric properties. Here the results are reported on experimental studies of energy harvested from (1-y-x)Pb(In1/2Nb1/2)O3–(y)Pb(Mg1/3Nb2/3)O3–(x)PbTiO3 (PIN-PMN-PT) crystals under high strain rate loading. Precise control of ferroelectric properties through composition, size and crystallographic orientation of domains made it possible to identify single crystals that release up to three times more electric charge density than that produced by PbZr0.52Ti0.48O3 (PZT 52/48) and PbZr0.95Ti0.05O3 (PZT 95/5) ferroelectric ceramics under identical loading conditions. The obtained results indicate that PIN-PMN-PT crystals became completely depolarized under 3.9 GPa compression. It was found that the energy density generated in the crystals during depolarization in the high voltage mode is four times higher than that for PZT 52/48 and 95/5. The obtained results promise new single crystal applications in ultrahigh-power transducers that are capable of producing hundreds kilovolt pulses and gigawatt-peak power microwave radiation. PMID:28440336

Quantitative calculations of fluorescence polarization and absorption anisotropy kinetics of double- and triple-chromophore complexes with energy transfer.

PubMed Central

Demidov, A A

1994-01-01

A new method is presented for calculation of the fluorescence depolarization and kinetics of absorption anisotropy for molecular complexes with a limited number of chromophores. The method considers absorption and emission of light by both chromophores, and also energy transfer between them, with regard to their mutual orientations. The chromophores in each individual complex are rigidly positioned. The complexes are randomly distributed and oriented in space, and there is no energy transfer between them. The new "practical" formula for absorption anisotropy and fluorescence depolarization kinetics, P(t) = [3B(t) - 1 + 2A(t)]/[3 + B(t) + 4A(t)], is derived both for double- and triple-chromophore complexes with delta-pulse excitation. The parameter B(t) is given by (a) B(t) = cos2(theta) for double-chromophore complexes, and (b) B(t) = q12(t)cos2(theta 12) + q13(t)-cos2(theta 13) + q23(t)cos2(theta 23) for triple-chromophore complexes, where q12(t) + q13(t) + q23(t) = 1. Here theta ij are the angles between the chromophore transition dipole moments in the individual molecular complex. The parameters qij(t) and A(t) are dependent on chromophore spectroscopic features and on the rates of energy transfer. PMID:7696461

Acute Ethanol Causes Hepatic Mitochondrial Depolarization in Mice: Role of Ethanol Metabolism

PubMed Central

Zhong, Zhi; Ramshesh, Venkat K.; Rehman, Hasibur; Liu, Qinlong; Theruvath, Tom P.; Krishnasamy, Yasodha; Lemasters, John J.

2014-01-01

Background/Aims An increase of ethanol metabolism and hepatic mitochondrial respiration occurs in vivo after a single binge of alcohol. Here, our aim was to determine how ethanol intake affects hepatic mitochondrial polarization status in vivo in relation to ethanol metabolism and steatosis. Methods Hepatic mitochondrial polarization, permeability transition (MPT), and reduce pyridine nucleotides, and steatosis in mice were monitored by intravital confocal/multiphoton microscopy of the fluorescence of rhodamine 123 (Rh123), calcein, NAD(P)H, and BODIPY493/503, respectively, after gavage with ethanol (1–6 g/kg). Results Mitochondria depolarized in an all-or-nothing fashion in individual hepatocytes as early as 1 h after alcohol. Depolarization was dose- and time-dependent, peaked after 6 to 12 h and maximally affected 94% of hepatocytes. This mitochondrial depolarization was not due to onset of the MPT. After 24 h, mitochondria of most hepatocytes recovered normal polarization and were indistinguishable from untreated after 7 days. Cell death monitored by propidium iodide staining, histology and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was low throughout. After alcohol, mitochondrial NAD(P)H autofluorescence increased and decreased, respectively, in hepatocytes with polarized and depolarized mitochondria. Ethanol also caused steatosis mainly in hepatocytes with depolarized mitochondria. Depolarization was linked to ethanol metabolism, since deficiency of alcohol dehydrogenase and cytochrome-P450 2E1 (CYP2E1), the major ethanol-metabolizing enzymes, decreased mitochondrial depolarization by ∼70% and ∼20%, respectively. Activation of aldehyde dehydrogenase decreased depolarization, whereas inhibition of aldehyde dehydrogenase enhanced depolarization. Activation of aldehyde dehydrogenase also markedly decreased steatosis. Conclusions Acute ethanol causes reversible hepatic mitochondrial depolarization in vivo that may contribute to steatosis and increased mitochondrial respiration. Onset of this mitochondrial depolarization is linked, at least in part, to metabolism of ethanol to acetaldehyde. PMID:24618581

Patterns of primary afferent depolarization of segmental and ascending intraspinal collaterals of single joint afferents in the cat.

PubMed

Rudomin, P; Lomelí, J

2007-01-01

We have examined in the anesthetized cat the threshold changes produced by sensory and supraspinal stimuli on intraspinal collaterals of single afferents from the posterior articular nerve (PAN). Forty-eight fibers were tested in the L3 segment, in or close to Clarke's column, and 70 fibers in the L6-L7 segments within the intermediate zone. Of these, 15 pairs of L3 and L6-L7 collaterals were from the same afferent. Antidromically activated fibers had conduction velocities between 23 and 74 m/s and peripheral thresholds between 1.1 and 4.7 times the threshold of the most excitable fibers (xT), most of them below 3 xT. PAN afferents were strongly depolarized by stimulation of muscle afferents and by cutaneous afferents, as well as by stimulation of the bulbar reticular formation and the midline raphe nuclei. Stimulation of muscle nerves (posterior biceps and semitendinosus, quadriceps) produced a larger PAD (primary afferent depolarization) in the L6-L7 than in the L3 terminations. Group II were more effective than group I muscle afferents. As with group I muscle afferents, the PAD elicited in PAN afferents by stimulation of muscle nerves could be inhibited by conditioning stimulation of cutaneous afferents. Stimulation of the cutaneous sural and superficial peroneal nerves increased the threshold of few terminations (i.e., produced primary afferent hyperpolarization, PAH) and reduced the threshold of many others, particularly of those tested in the L6-L7 segments. Yet, there was a substantial number of terminals where these conditioning stimuli had minor or no effects. Autogenetic stimulation of the PAN with trains of pulses increased the intraspinal threshold in 46% and reduced the threshold in 26% of fibers tested in the L6-L7 segments (no tests were made with trains of pulses on fibers ending in L3). These observations indicate that PAN afferents have a rather small autogenetic PAD, particularly if this is compared with the effects of heterogenetic stimulation. Therefore, the depression of the PAN intraspinal fields produced by autogenetic stimulation described by Rudomin et al. (Exp Brain Res DOI 10.1007/s00221-006-0600-x, 2006) may be ascribed to other mechanisms besides a GABAa PAD. It is suggested that the small or no autogenetic PAD displayed by the examined joint afferents prevents presynaptic filtering of their synaptic actions and preserves the original information generated in the periphery. This could be important for proper adjustment of limb position.

Depolarizing actions of GABA in immature neurons depend neither on ketone bodies nor on pyruvate.

PubMed

Tyzio, Roman; Allene, Camille; Nardou, Romain; Picardo, Michel A; Yamamoto, Sumii; Sivakumaran, Sudhir; Caiati, Maddalena D; Rheims, Sylvain; Minlebaev, Marat; Milh, Mathieu; Ferré, Pascal; Khazipov, Rustem; Romette, Jean-Louis; Lorquin, Jean; Cossart, Rosa; Khalilov, Ilgam; Nehlig, Astrid; Cherubini, Enrico; Ben-Ari, Yehezkel

2011-01-05

GABA depolarizes immature neurons because of a high [Cl(-)](i) and orchestrates giant depolarizing potential (GDP) generation. Zilberter and coworkers (Rheims et al., 2009; Holmgren et al., 2010) showed recently that the ketone body metabolite DL-3-hydroxybutyrate (DL-BHB) (4 mM), lactate (4 mM), or pyruvate (5 mM) shifted GABA actions to hyperpolarizing, suggesting that the depolarizing effects of GABA are attributable to inadequate energy supply when glucose is the sole energy source. We now report that, in rat pups (postnatal days 4-7), plasma D-BHB, lactate, and pyruvate levels are 0.9, 1.5, and 0.12 mM, respectively. Then, we show that DL-BHB (4 mM) and pyruvate (200 μM) do not affect (i) the driving force for GABA(A) receptor-mediated currents (DF(GABA)) in cell-attached single-channel recordings, (2) the resting membrane potential and reversal potential of synaptic GABA(A) receptor-mediated responses in perforated patch recordings, (3) the action potentials triggered by focal GABA applications, or (4) the GDPs determined with electrophysiological recordings and dynamic two-photon calcium imaging. Only very high nonphysiological concentrations of pyruvate (5 mM) reduced DF(GABA) and blocked GDPs. Therefore, DL-BHB does not alter GABA signals even at the high concentrations used by Zilberter and colleagues, whereas pyruvate requires exceedingly high nonphysiological concentrations to exert an effect. There is no need to alter conventional glucose enriched artificial CSF to investigate GABA signals in the developing brain.

A 20 Ghz Depolarization Experiment Using the ATS-6 Satellite

NASA Technical Reports Server (NTRS)

Bostian, C. W.; Manus, E. A.; Marshall, R. E.; Pendrak, H. N.; Stutzman, W. L.; Wiley, P. H.; Kauffman, S. R.

1975-01-01

A depolarization experiment using the 20 GHz downlink from the ATS-6 satellite was described. The following subjects were covered: (1) an operational summary of the experiment, (2) a description of the equipment used with emphasis on improvements made to the signal processing receiver used with the ATS-5 satellite, (3) data on depolarization and attenuation in one snow storm and two rain storms at 45 deg elevation, (4) data on low angle propagation, (5) conclusions about depolarization on satellite paths, and (6) recommendations for the depolarization portion of the CTS experiment.

RGK protein-mediated impairment of slow depolarization- dependent Ca2+ entry into developing myotubes

PubMed Central

Romberg, Christin F; Beqollari, Donald; Meza, Ulises; Bannister, Roger A

2014-01-01

Three physiological functions have been described for the skeletal muscle 1,4-dihydropyridine receptor (CaV1.1): (1) voltage-sensor for excitation-contraction (EC) coupling, (2) L-type Ca2+ channel, and (3) voltage-sensor for slow depolarization-dependent Ca2+ entry. Members of the RGK (Rad, Rem, Rem2, Gem/Kir) family of monomeric GTP-binding proteins are potent inhibitors of the former two functions of CaV1.1. However, it is not known whether the latter function that has been attributed to CaV1.1 is subject to modulation by RGK proteins. Thus, the purpose of this study was to determine whether Rad, Gem and/or Rem inhibit the slowly developing, persistent Ca2+ entry that is dependent on the voltage-sensing capability of CaV1.1. As a means to investigate this question, Venus fluorescent protein-fused RGK proteins (V-Rad, V-Rem and V-Gem) were overexpressed in “normal” mouse myotubes. We observed that such overexpression of V-Rad, V-Rem or V-Gem in myotubes caused marked changes in morphology of the cells. As shown previously for YFP-Rem, both L-type current and EC coupling were also impaired greatly in myotubes expressing either V-Rad or V-Gem. The reductions in L-type current and EC coupling were paralleled by reductions in depolarization-induced Ca2+ entry. Our observations provide the first evidence of modulation of this enigmatic Ca2+ entry pathway peculiar to skeletal muscle. PMID:24476902

Thermally stimulated depolarization currents and dielectric properties of Mg0.95Ca0.05TiO3 filled HDPE composites

NASA Astrophysics Data System (ADS)

Shi, Yunzhou; Zhang, Li; Zhang, Jie; Yue, Zhenxing

2017-12-01

Mg0.95Ca0.05TiO3 (MCT) filled high density polyethylene (HDPE) composites were prepared by twin-screw extrusion followed by hot pressing technique. The thermally stimulated depolarization current (TSDC) measurement was performed to analyze the contribution of charge distribution and interfacial characteristics to the dielectric loss. TSDC spectra under different polarization conditions show that the introduction of ceramic fillers engenders shallow traps in the vicinity of ceramic-polymer interface, which hinders the injection of space charge from the electrode into the polymer matrix. In the composite materials applied to an external field, charges tend to be captured by these traps. The temperature dependence of relative permittivity and dielectric loss of the composites was measured, and a strong reliance of dielectric loss on temperature was observed. In the heating process, the release of charges accumulating at interfacial region is considered to contribute to the rise in dielectric loss with the increase of temperature.

Effects of S(+)-efonidipine on the rabbit sinus node action potential and calcium channel subunits Ca(V)1.2, Ca(V)1.3 and Ca(V)3.1.

PubMed

Tanaka, Hikaru; Namekata, Iyuki; Ogawa, Toru; Tsuneoka, Yayoi; Komikado, Chisa; Takahara, Akira; Iida-Tanaka, Naoko; Izumi-Nakaseko, Hiroko; Tsuru, Hiromichi; Adachi-Akahane, Satomi

2010-12-15

The effect of S(+)-efonidipine on sinus node action potential and calcium channel α-subunits was examined. The slope of the phase 4 depolarization of isolated rabbit sinus node tissue was significantly reduced by S(+)-efonidipine (1 μM), slightly reduced by nifedipine (1 μM), but was not affected by R(-)-efonidipine. S(+)-efonidipine (1 μM), inhibited the expressed Ca(V)1.2, Ca(V)1.3 and Ca(V)3.1 channel currents by 75.7%, 75.3% and 94.0%, nifedipine 84.0%, 43.2% and 14.9%, and R(-)-efonidipine 30.0%, 19.6% and 92.8%, respectively. Thus, the prolongation of the phase 4 depolarization of the rabbit sinus node by S(+)-efonidipine may be explained by blockade of the Ca(V)1.3 channel current. Copyright © 2010 Elsevier B.V. All rights reserved.

Multiple scattering of broadband terahertz pulses

NASA Astrophysics Data System (ADS)

Pearce, Jeremiah Glen

Propagation of single-cycle terahertz (THz) pulses through a random medium leads to dramatic amplitude and phase variations of the electric field because of multiple scattering. We present the first set of experiments that investigate the propagation of THz pulses through scattering media. The scattering of short pulses is a relevant subject to many communities in science and engineering, because the properties of multiply scattered or diffuse waves provide insights into the characteristics of the random medium. For example, the depolarization of diffuse waves has been used to form images of objects embedded in inhomogeneous media. Most of the previous scattering experiments have used narrowband optical radiation where measurements are limited to time averaged intensities or autocorrelation quantities, which contain no phase information of the pulses. In the experiments presented here, a terahertz time-domain spectrometer (THz-TDS) is used. A THz-TDS propagates single-cycle sub-picosecond pulses with bandwidths of over 1 THz into free space. The THz-TDS is a unique tool to study such phenomena, because it provides access to both the intensity and phase of those pulses through direct measurement of the temporal electric field. Because of the broad bandwidth and linear phase of the pulses, it is possible to simultaneously study Rayleigh scattering and the short wavelength limit in a single measurement. We study the diffusion of broadband single-cycle THz pulses by propagating the pulses through a highly scattering medium. Using the THz-TDS, time-domain measurements provide information on the statistics of both the amplitude and phase of the diffusive waves. We develop a theoretical description, suitable for broadband radiation, which accurately describes the experimental results. We measure the time evolution of the degree of polarization, and directly correlate it with the single-scattering regime in the time domain. Measurements of the evolution of the temporal phase of the radiation demonstrate that the average spectral content depends on the state of polarization. In the case of broadband radiation, this effect distinguishes photons that have been scattered only a few times from those that are propagating diffusively.

Polarimetric imaging of retinal disease by polarization sensitive SLO

NASA Astrophysics Data System (ADS)

Miura, Masahiro; Elsner, Ann E.; Iwasaki, Takuya; Goto, Hiroshi

2015-03-01

Polarimetry imaging is used to evaluate different features of the macular disease. Polarimetry images were recorded using a commercially- available polarization-sensitive scanning laser opthalmoscope at 780 nm (PS-SLO, GDx-N). From data sets of PS-SLO, we computed average reflectance image, depolarized light images, and ratio-depolarized light images. The average reflectance image is the grand mean of all input polarization states. The depolarized light image is the minimum of crossed channel. The ratio-depolarized light image is a ratio between the average reflectance image and depolarized light image, and was used to compensate for variation of brightness. Each polarimetry image is compared with the autofluorescence image at 800 nm (NIR-AF) and autofluorescence image at 500 nm (SW-AF). We evaluated four eyes with geographic atrophy in age related macular degeneration, one eye with retinal pigment epithelium hyperplasia, and two eyes with chronic central serous chorioretinopathy. Polarization analysis could selectively emphasize different features of the retina. Findings in ratio depolarized light image had similarities and differences with NIR-AF images. Area of hyper-AF in NIR-AF images showed high intensity areas in the ratio depolarized light image, representing melanin accumulation. Areas of hypo-AF in NIR-AF images showed low intensity areas in the ratio depolarized light images, representing melanin loss. Drusen were high-intensity areas in the ratio depolarized light image, but NIR-AF images was insensitive to the presence of drusen. Unlike NIR-AF images, SW-AF images showed completely different features from the ratio depolarized images. Polarization sensitive imaging is an effective tool as a non-invasive assessment of macular disease.

Effects of interleukin-1ß on cortical spreading depolarization and cerebral vasculature

PubMed Central

Eitner, Annett; Leuchtweis, Johannes; Bauer, Reinhard; Lehmenkühler, Alfred; Schaible, Hans-Georg

2016-01-01

During brain damage and ischemia, the cytokine interleukin-1ß is rapidly upregulated due to activation of inflammasomes. We studied whether interleukin-1ß influences cortical spreading depolarization, and whether lipopolysaccharide, often used for microglial stimulation, influences cortical spreading depolarizations. In anaesthetized rats, cortical spreading depolarizations were elicited by microinjection of KCl. Interleukin-1ß, the IL-1 receptor 1 antagonist, the GABAA receptor blocker bicuculline, and lipopolysaccharide were administered either alone or combined (interleukin-1ß + IL-1 receptor 1 antagonist; interleukin-1ß + bicuculline; lipopolysaccharide + IL-1 receptor 1 antagonist) into a local cortical treatment area. Using microelectrodes, cortical spreading depolarizations were recorded in a non-treatment and in the treatment area. Plasma extravasation in cortical grey matter was assessed with Evans blue. Local application of interleukin-1ß reduced cortical spreading depolarization amplitudes in the treatment area, but not at a high dose. This reduction was prevented by IL-1 receptor 1 antagonist and by bicuculline. However, interleukin-1ß induced pronounced plasma extravasation independently on cortical spreading depolarizations. Application of lipopolysaccharide reduced cortical spreading depolarization amplitudes but prolonged their duration; EEG activity was still present. These effects were also blocked by IL-1 receptor 1 antagonist. Interleukin-1ß evokes changes of neuronal activity and of vascular functions. Thus, although the reduction of cortical spreading depolarization amplitudes at lower doses of interleukin-1ß may reduce deleterious effects of cortical spreading depolarizations, the sum of interleukin-1ß effects on excitability and on the vasculature rather promote brain damaging mechanisms. PMID:27037093

Mechanisms and roles of muscarinic activation in guinea-pig adrenal medullary cells.

PubMed

Inoue, Masumi; Harada, Keita; Matsuoka, Hidetada; Nakamura, Jun; Warashina, Akira

2012-09-15

Muscarinic receptors are expressed in the adrenal medullary (AM) cells of various mammals, but their physiological roles are controversial. Therefore, the ionic mechanism for muscarinic receptor-mediated depolarization and the role of muscarinic receptors in neuronal transmission were investigated in dissociated guinea-pig AM cells and in the perfused guinea-pig adrenal gland. Bath application of muscarine induced an inward current at -60 mV. This inward current was partially suppressed by quinine with an IC(50) of 6.1 μM. The quinine-insensitive component of muscarine-induced currents changed the polarity at -78 mV and was inhibited by bupivacaine, a TWIK-related acid-sensitive K(+) (TASK) channel inhibitor. Conversely, the current-voltage relationship for the bupivacaine-insensitive component of muscarine currents showed a reversal potential of -5 mV and a negative slope below -40 mV. External application of La(3+) had a double action on muscarine currents of both enhancement and suppression. Immunoblotting and immunocytochemistry revealed expression of TASK1 channels and cononical transient receptor potential channels 1, 4, 5, and 7 in guinea-pig AM cells. Retrograde application of atropine reversibly suppressed transsynaptically evoked catecholamine secretion from the adrenal gland. The results indicate that muscarinic receptor stimulation in guinea-pig AM cells induces depolarization through inhibition of TASK channels and activation of nonselective cation channels and that muscarinic receptors are involved in neuronal transmission from the splanchnic nerve.

Frequency doubled high-power disk lasers in pulsed and continuous-wave operation

NASA Astrophysics Data System (ADS)

Weiler, Sascha; Hangst, Alexander; Stolzenburg, Christian; Zawischa, Ivo; Sutter, Dirk; Killi, Alexander; Kalfhues, Steffen; Kriegshaeuser, Uwe; Holzer, Marco; Havrilla, David

2012-03-01

The disk laser with multi-kW output power in infrared cw operation is widely used in today's manufacturing, primarily in the automotive industry. The disk technology combines high power (average and/or peak power), excellent beam quality, high efficiency and high reliability with low investment and operating costs. Additionally, the disk laser is ideally suited for frequency conversion due to its polarized output with negligible depolarization losses. Laser light in the green spectral range (~515 nm) can be created with a nonlinear crystal. Pulsed disk lasers with green output of well above 50 W (extracavity doubling) in the ps regime and several hundreds of Watts in the ns regime with intracavity doubling are already commercially available whereas intracavity doubled disk lasers in continuous wave operation with greater than 250 W output are in test phase. In both operating modes (pulsed and cw) the frequency doubled disk laser offers advantages in existing and new applications. Copper welding for example is said to show much higher process reliability with green laser light due to its higher absorption in comparison to the infrared. This improvement has the potential to be very beneficial for the automotive industry's move to electrical vehicles which requires reliable high-volume welding of copper as a major task for electro motors, batteries, etc.

Open channel block of A-type, kv4.3, and delayed rectifier K+ channels, Kv1.3 and Kv3.1, by sibutramine.

PubMed

Kim, Sung Eun; Ahn, Hye Sook; Choi, Bok Hee; Jang, Hyun-Jong; Kim, Myung-Jun; Rhie, Duck-Joo; Yoon, Shin-Hee; Jo, Yang-Hyeok; Kim, Myung-Suk; Sung, Ki-Wug; Hahn, Sang June

2007-05-01

The effects of sibutramine on voltage-gated K+ channel (Kv)4.3, Kv1.3, and Kv3.1, stably expressed in Chinese hamster ovary cells, were investigated using the whole-cell patch-clamp technique. Sibutramine did not significantly decrease the peak Kv4.3 currents, but it accelerated the rate of decay of current inactivation in a concentration-dependent manner. This phenomenon was effectively characterized by integrating the total current over the duration of a depolarizing pulse to +40 mV. The IC50 value for the sibutramine block of Kv4.3 was 17.3 microM. Under control conditions, the inactivation of Kv4.3 currents could be fit to a biexponential function, and the time constants for the fast and slow components were significantly decreased after the application of sibutramine. The association (k+1) and dissociation (k-1) rate constants for the sibutramine block of Kv 4.3 were 1.51 microM-1s-1 and 27.35 s-1, respectively. The theoretical KD value, derived from k-1/k+1, yielded a value of 18.11 microM. The block of Kv4.3 by sibutramine displayed a weak voltage dependence, increasing at more positive potentials, and it was use-dependent at 2 Hz. Sibutramine did not affect the time course for the deactivating tail currents. Neither steady-state activation and inactivation nor the recovery from inactivation was affected by sibutramine. Sibutramine caused the concentration-dependent block of the Kv1.3 and Kv3.1 currents with an IC50 value of 3.7 and 32.7 microM, respectively. In addition, sibutramine reduced the tail current amplitude and slowed the deactivation of the tail currents of Kv1.3 and Kv3.1, resulting in a crossover phenomenon. These results indicate that sibutramine acts on Kv4.3, Kv1.3, and Kv3.1 as an open channel blocker.

Activation state of the hyperpolarization-activated current modulates temperature-sensitivity of firing in locus coeruleus neurons from bullfrogs.

PubMed

Santin, Joseph M; Hartzler, Lynn K

2015-06-15

Locus coeruleus neurons of anuran amphibians contribute to breathing control and have spontaneous firing frequencies that, paradoxically, increase with cooling. We previously showed that cooling inhibits a depolarizing membrane current, the hyperpolarization-activated current (I h) in locus coeruleus neurons from bullfrogs, Lithobates catesbeianus (Santin JM, Watters KC, Putnam RW, Hartzler LK. Am J Physiol Regul Integr Comp Physiol 305: R1451-R1464, 2013). This suggests an unlikely role for I h in generating cold activation, but led us to hypothesize that inhibition of I h by cooling functions as a physiological brake to limit the cold-activated response. Using whole cell electrophysiology in brain slices, we employed 2 mM Cs(+) (an I h antagonist) to isolate the role of I h in spontaneous firing and cold activation in neurons recorded with either control or I h agonist (cyclic AMP)-containing artificial intracellular fluid. I h did not contribute to the membrane potential (V m) and spontaneous firing at 20°C. Although voltage-clamp analysis confirmed that cooling inhibits I h, its lack of involvement in setting baseline firing and V m precluded its ability to regulate cold activation as hypothesized. In contrast, neurons dialyzed with cAMP exhibited greater baseline firing frequencies at 20°C due to I h activation. Our hypothesis was supported when the starting level of I h was enhanced by elevating cAMP because cold activation was converted to more ordinary cold inhibition. These findings indicate that situations leading to enhancement of I h facilitate firing at 20°C, yet the hyperpolarization associated with inhibiting a depolarizing cation current by cooling blunts the net V m response to cooling to oppose normal cold-depolarizing factors. This suggests that the influence of I h activation state on neuronal firing varies in the poikilothermic neuronal environment. Copyright © 2015 the American Physiological Society.

Incidence, hemodynamic, and electrical characteristics of spreading depolarization in a swine model are affected by local but not by intravenous application of magnesium.

PubMed

Santos, Edgar; León, Fiorella; Silos, Humberto; Sanchez-Porras, Renan; Shuttleworth, C William; Unterberg, Andreas; Sakowitz, Oliver W

2016-12-01

The aim was to characterize the effects of magnesium sulfate, using i.v. bolus and local administration, using intrinsic signal imaging, and on electrocorticographic activity during the induction and propagation of spreading depolarizations in the gyrencephalic porcine brain. Local application of magnesium sulfate led to a complete inhibition of spreading depolarizations. One hour after washing out the topical magnesium sulfate, re-incidence of the spreading depolarizations was observed in 50% of the hemispheres. Those spreading depolarizations showed attenuation in hemodynamic characteristics and speed in intrinsic optical signal imaging. The electrical amplitude decreased through electrocorticographic activity. Intravenous magnesium therapy showed no significant effects on spreading depolarization incidence and characteristics. © The Author(s) 2016.

The role of BK-type Ca2+-dependent K+ channels in spike broadening during repetitive firing in rat hippocampal pyramidal cells

PubMed Central

Shao, Li-Rong; Halvorsrud, Ragnhild; Borg-Graham, Lyle; Storm, Johan F

1999-01-01

The role of large-conductance Ca2+-dependent K+ channels (BK-channels; also known as maxi-K- or slo-channels) in spike broadening during repetitive firing was studied in CA1 pyramidal cells, using sharp electrode intracellular recordings in rat hippocampal slices, and computer modelling. Trains of action potentials elicited by depolarizing current pulses showed a progressive, frequency-dependent spike broadening, reflecting a reduced rate of repolarization. During a 50 ms long 5 spike train, the spike duration increased by 63·6 ± 3·4% from the 1st to the 3rd spike. The amplitude of the fast after-hyperpolarization (fAHP) also rapidly declined during each train. Suppression of BK-channel activity with (a) the selective BK-channel blocker iberiotoxin (IbTX, 60 nM), (b) the non-peptidergic BK-channel blocker paxilline (2–10 μM), or (c) calcium-free medium, broadened the 1st spike to a similar degree (≈60%). BK-channel suppression also caused a similar change in spike waveform as observed during repetitive firing, and eliminated (occluded) most of the spike broadening during repetitive firing. Computer simulations using a reduced compartmental model with transient BK-channel current and 10 other active ionic currents, produced an activity-dependent spike broadening that was strongly reduced when the BK-channel inactivation mechanism was removed. These results, which are supported by recent voltage-clamp data, strongly suggest that in CA1 pyramidal cells, fast inactivation of a transient BK-channel current (ICT), substantially contributes to frequency-dependent spike broadening during repetitive firing. PMID:10562340

Intrinsic cytosolic calcium buffering properties of single rat cardiac myocytes.

PubMed Central

Berlin, J R; Bassani, J W; Bers, D M

1994-01-01

Intracellular passive Ca2+, buffering was measured in voltage-clamped rat ventricular myocytes. Cells were loaded with indo-1 (K+ salt) to an estimated cytosolic concentration of 44 +/- 5 microM (Mean +/- SEM, n = 5), and accessible cell volume was estimated to be 24.5 +/- 3.6 pl. Ca2+ transport by the sarcoplasmic reticulum (SR) Ca-ATPase and sarcolemmal Na-Ca exchange was inhibited by treatment with thapsigargin and Na-free solutions, respectively. Extracellular [Ca2+] was maintained at 10 mM and, in some experiments, the mitochondrial uncoupler "1799" was used to assess the degree of mitochondrial Ca2+ uptake. To perform single cell titrations, intracellular Ca2+ ([Ca2+]i) was increased progressively by a train of depolarizing voltage clamp pulses from -40 to +10 mV. The total Ca2+ gain with each pulse was calculated by integration of the Ca current and then analyzed as a function of the rapid change in [Ca2+]i during the pulse. In the range of [Ca2+]i from 0.1 to 2 microM, overall cell buffering was well described as a single lumped Michaelis-Menten type species with an apparent dissociation constant, KD, of of 0.63 +/- 0.07 microM (n = 5) and a binding capacity, Bmax, of 162 +/- 15 mumol/l cell H2O. Correction for buffering attributable to cytosolic indo-1 gives intrinsic cytosolic Ca2+ buffering parameters of KD = 0.96 +/- 0.18 microM and Bmax = 123 +/- 18 mumol/l cell H2O. The fast Ca2+ buffering measured in this manner agrees reasonably with the characteristics of known rapid Ca buffers (e.g., troponin C, calmodulin, and SR Ca-ATPase), but is only about half of the total Ca2+ buffering measured at equilibrium. Inclusion of slow Ca buffers such as the Ca/Mg sites on troponin C and myosin can account for the differences between fast Ca2+ buffering in phase with the Ca current measured in the present experiments and equilibrium Ca2+ buffering. The present data indicate that a rapid rise of [Ca2+]i from 0.1 to 1 microM during a contraction requires approximately 50 microM Ca2+ to be added to the cytosol. PMID:7819510

Dynamical characterization of inactivation path in voltage-gated Na+ ion channel by non-equilibrium response spectroscopy

PubMed Central

Pal, Krishnendu; Gangopadhyay, Gautam

2016-01-01

ABSTRACT Inactivation path of voltage gated sodium channel has been studied here under various voltage protocols as it is the main governing factor for the periodic occurrence and shape of the action potential. These voltage protocols actually serve as non-equilibrium response spectroscopic tools to study the ion channel in non-equilibrium environment. In contrast to a lot of effort in finding the crystal structure based molecular mechanism of closed-state(CSI) and open-state inactivation(OSI); here our approach is to understand the dynamical characterization of inactivation. The kinetic flux as well as energetic contribution of the closed and open- state inactivation path is compared here for voltage protocols, namely constant, pulsed and oscillating. The non-equilibrium thermodynamic quantities used in response to these voltage protocols serve as improved characterization tools for theoretical understanding which not only agrees with the previously known kinetic measurements but also predict the energetically optimum processes to sustain the auto-regulatory mechanism of action potential and the consequent inactivation steps needed. The time dependent voltage pattern governs the population of the conformational states which when couple with characteristic rate parameters, the CSI and OSI selectivity arise dynamically to control the inactivation path. Using constant, pulsed and continuous oscillating voltage protocols we have shown that during depolarization the OSI path is more favored path of inactivation however, in the hyper-polarized situation the CSI is favored. It is also shown that the re-factorisation of inactivated sodium channel to resting state occurs via CSI path. Here we have shown how the subtle energetic and entropic cost due to the change in the depolarization magnitude determines the optimum path of inactivation. It is shown that an efficient CSI and OSI dynamical profile in principle can characterize the open-state drug blocking phenomena. PMID:27367642

Electrogenic active proton pump in Rana esculenta skin and its role in sodium ion transport.

PubMed

Ehrenfeld, J; Garcia-Romeu, F; Harvey, B J

1985-02-01

Kinetic and electrophysiological studies were carried out in the in vitro Rana esculenta skin, bathed in dilute sodium solution, to characterize the proton pump and coupling between sodium absorption (JNa+n) and proton excretion (JH+n). JNa+n and JH+n were both dependent on transepithelial potential (psi ms); hyperpolarizing the skin decreased JNa+n and increased JH+n; depolarization produced the opposite effects. Amiloride (5 X 10(-5) M) at a clamped psi ms of +50 mV inhibited JNa+n without affecting JH+n. Variations of psi ms or pH had identical effects on JH+n. Ethoxzolamide inhibited JH+n and simultaneously increased psi ms by 15-30 mV. These changes were accompanied by depolarization of the apical membrane potential psi mc from -47 to -25 mV and an increase in apical membrane resistance of 30%; no significant effects on basolateral membrane potential (psi cs) and resistance (Rb) nor on shunt resistance (Rj) were observed. The proton pump appears to be localized at the apical membrane. The proton pump was also inhibited by deoxygenation, oligomycin, dicyclohexylcarbodiimide and vanadate (100, 78, 83 and 100% inhibition respectively). The variations of JH+n and of the measured electrical currents were significantly correlated. These findings are supportive evidence of a primary active proton pump, electrogenic and strictly linked to aerobic metabolism. The current-voltage (I-V) relation of the proton pump was obtained as the difference in the I-V curves of the apical membrane extracted before and after proton-pump inhibition by ethoxzolamide during amiloride block of sodium transport. The proton-pump current (IP) was best described by a saturable exponential function of psi mc. Maximal pump current (ImaxP) was calculated to be 200 nequiv h-1 cm-2 at a psi mc of +50 mV and the pump reversal potential ERP was -130 mV. The effect of ethoxzolamide to depolarize psi mc was dependent on the relation between psi mc and ERP. Maximal induced depolarization occurred at a psi mc of +50 mV whereas ethoxzolamide exerted minimal effect on psi mc when the ERP was approached either by voltage clamping the apical membrane or by the addition of amiloride. We show that electroneutral sodium-proton countertransport is not the mechanism of active proton excretion in frog skin but that it is the proton excretion which provides a favourable electrical driving force for passive apical sodium entry.(ABSTRACT TRUNCATED AT 400 WORDS)

Electrogenic active proton pump in Rana esculenta skin and its role in sodium ion transport.

PubMed Central

Ehrenfeld, J; Garcia-Romeu, F; Harvey, B J

1985-01-01

Kinetic and electrophysiological studies were carried out in the in vitro Rana esculenta skin, bathed in dilute sodium solution, to characterize the proton pump and coupling between sodium absorption (JNa+n) and proton excretion (JH+n). JNa+n and JH+n were both dependent on transepithelial potential (psi ms); hyperpolarizing the skin decreased JNa+n and increased JH+n; depolarization produced the opposite effects. Amiloride (5 X 10(-5) M) at a clamped psi ms of +50 mV inhibited JNa+n without affecting JH+n. Variations of psi ms or pH had identical effects on JH+n. Ethoxzolamide inhibited JH+n and simultaneously increased psi ms by 15-30 mV. These changes were accompanied by depolarization of the apical membrane potential psi mc from -47 to -25 mV and an increase in apical membrane resistance of 30%; no significant effects on basolateral membrane potential (psi cs) and resistance (Rb) nor on shunt resistance (Rj) were observed. The proton pump appears to be localized at the apical membrane. The proton pump was also inhibited by deoxygenation, oligomycin, dicyclohexylcarbodiimide and vanadate (100, 78, 83 and 100% inhibition respectively). The variations of JH+n and of the measured electrical currents were significantly correlated. These findings are supportive evidence of a primary active proton pump, electrogenic and strictly linked to aerobic metabolism. The current-voltage (I-V) relation of the proton pump was obtained as the difference in the I-V curves of the apical membrane extracted before and after proton-pump inhibition by ethoxzolamide during amiloride block of sodium transport. The proton-pump current (IP) was best described by a saturable exponential function of psi mc. Maximal pump current (ImaxP) was calculated to be 200 nequiv h-1 cm-2 at a psi mc of +50 mV and the pump reversal potential ERP was -130 mV. The effect of ethoxzolamide to depolarize psi mc was dependent on the relation between psi mc and ERP. Maximal induced depolarization occurred at a psi mc of +50 mV whereas ethoxzolamide exerted minimal effect on psi mc when the ERP was approached either by voltage clamping the apical membrane or by the addition of amiloride. We show that electroneutral sodium-proton countertransport is not the mechanism of active proton excretion in frog skin but that it is the proton excretion which provides a favourable electrical driving force for passive apical sodium entry.(ABSTRACT TRUNCATED AT 400 WORDS) Images Fig. 6 Fig. 7 PMID:2582114

Depolarization on Earth-space paths

NASA Technical Reports Server (NTRS)

1981-01-01

Sources of depolarization effects on the propagation paths of orthogonally-polarized information channels are considered. The main sources of depolarization at millimeter wave frequencies are hydrometeor absorption and scattering in the troposphere. Terms are defined. Mathematical formulations for the effects of the propagation medium characteristics and antenna performance on signals in dual polarization Earth-space links are presented. Techniques for modeling rain and ice depolarization are discussed.

Role of calcium stores and membrane voltage in the generation of slow wave action potentials in guinea-pig gastric pylorus

PubMed Central

Van Helden, D F; Imtiaz, M S; Nurgaliyeva, K; von der Weid, P-Y; Dosen, P J

2000-01-01

Intracellular recordings made in single bundle strips of a visceral smooth muscle revealed rhythmic spontaneous membrane depolarizations termed slow waves (SWs). These exhibited ‘pacemaker’ and ‘regenerative’ components composed of summations of more elementary events termed spontaneous transient depolarizations (STDs). STDs and SWs persisted in the presence of tetrodotoxin, nifedipine and ryanodine, and upon brief exposure to Ca2+-free Cd2+-containing solutions; they were enhanced by ACh and blocked by BAPTA AM, cyclopiazonic acid and caffeine. SWs were also inhibited in heparin-loaded strips. SWs were observed over a wide range of membrane potentials (e.g. −80 to −45 mV) with increased frequencies at more depolarized potentials. Regular spontaneous SW activity in this preparation began after 1–3 h superfusion of the tissue with physiological saline following the dissection procedure. Membrane depolarization applied before the onset of this activity induced bursts of STD-like events (termed the ‘initial’ response) which, when larger than threshold levels initiated regenerative responses. The combined initial-regenerative waveform was termed the SW-like action potential. Voltage-induced responses exhibited large variable latencies (typical range 0.3–4 s), refractory periods of ≈11 s and a pharmacology that was indistinguishable from those of STDs and spontaneous SWs. The data indicate that SWs arise through more elementary inositol 1,4,5-trisphosphate (IP3) receptor-induced Ca2+ release events which rhythmically synchronize to trigger regenerative Ca2+ release and induce inward current across the plasmalemma. The finding that action potentials, which were indistinguishable from SWs, could be evoked by depolarization suggests that membrane potential modulates IP3 production. Voltage feedback on intracellular IP3-sensitive Ca2+ release is likely to have a major influence on the generation and propagation of SWs. PMID:10747196

The retrieval of the Asian dust depolarization ratio in Korea with the correction of the polarization-dependent transmission

NASA Astrophysics Data System (ADS)

Shin, Sungkyun; Müller, Detlef; Kim, Y. J.; Tatarov, Boyan; Shin, Dongho; Seifert, Patric; Noh, Young Min

2013-01-01

The linear particle depolarization ratios were retrieved from the observation with a multiwavelength Raman lidar at the Gwangju Institute of Science and Technology (GIST), Korea (35.11°N, 126.54°E). The measurements were carried out in spring (March to May) 2011. The transmission ratio measurements were performed to solve problems of the depolarization-dependent transmission at a receiver of the lidar and applied to correct the retrieved depolarization ratio of Asian dust at first time in Korea. The analyzed data from the GIST multiwavelength Raman lidar were classified into three categories according to the linear particle depolarization ratios, which are pure Asian dust on 21 March, the intermediate case which means Asian dust mixed with urban pollution on 13 May, and haze case on 10 April. The measured transmission ratios were applied to these cases respectively. We found that the transmission ratio is needed to be used to retrieve the accurate depolarization ratio of Asian dust and also would be useful to distinguish the mixed dust particles between intermediate case and haze. The particle depolarization ratios of pure Asian dust were approximately 0.25 at 532 nm and 0.14 at 532 nm for the intermediate case. The linear particle depolarization ratios of pure Asian dust observed with the GIST multiwavelength Raman lidar were compared to the linear particle depolarization ratios of Saharan dust observed in Morocco and Asian dust observed both in Japan and China.

Nitric oxide decreases the excitability of interstitial cells of Cajal through activation of the BK channel

PubMed Central

Zhu, Yaohui; Huizinga, Jan D

2008-01-01

Abstract Nitrergic nerves are structurally and functionally associated with ICC. To further understand mechanisms of communication, the hypothesis was investigated that NO might affect large conductance K channels. To that end, we searched for IbTX-sensitive currents in ICC obtained through explant cultures from the mouse small intestine and studied effects of the NOS inhibitor omega N-nitro-L-arginine (LNNA) and the NO donor sodium nitroprusside (SNP). IbTX-sensitive currents acquired in the whole-cell configuration through nystatin perforated patches exhibited high noise levels but relatively low amplitude, whereas currents obtained in the conventional whole-cell configuration exhibited less noise and higher amplitudes; depolarization from −80 to + 40 mV evoked 357 ± 159 pA current in the nystatin perforated patch configuration and 1075 ± 597 pA using the conventional whole-cell configuration. Immunohistochemistry showed that ICC associated with ganglia and Auerbach's plexus nerve fibers were immunoreactive to BK antibodies. The IbTX-sensitive currents were increased by SNP and inhibited by LNNA. BK blockers suppressed spontaneous transit outward currents in ICC. After block of BK currents, or before these currents became prominent, calcium currents were activated by depolarization in the same cells. Their peak amplitude occurred at −25 mV and the currents were increased with increasing extracellular calcium and inhibited by cobalt. The hypothesis is warranted that nitrergic innervation inhibits ICC excitability in part through activation of BK channels. In addition, NO is an intracellular regulator of ICC excitability. PMID:18194464

Induced polarized state in intentionally grown oxygen deficient KTaO{sub 3} thin films

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mota, D. A.; Romaguera-Barcelay, Y.; Tkach, A.

2013-07-21

Deliberately oxygen deficient potassium tantalate thin films were grown by RF magnetron sputtering on Si/SiO{sub 2}/Ti/Pt substrates. Once they were structurally characterized, the effect of oxygen vacancies on their electric properties was addressed by measuring leakage currents, dielectric constant, electric polarization, and thermally stimulated depolarization currents. By using K{sub 2}O rich KTaO{sub 3} targets and specific deposition conditions, KTaO{sub 3-{delta}} oxygen deficient thin films with a K/Ta = 1 ratio were obtained. Room temperature X-ray diffraction patterns show that KTaO{sub 3-{delta}} thin films are under a compressive strain of 2.3% relative to KTaO{sub 3} crystals. Leakage current results reveal themore » presence of a conductive mechanism, following the Poole-Frenkel formalism. Furthermore, dielectric, polarization, and depolarization current measurements yield the existence of a polarized state below T{sub pol} {approx} 367 Degree-Sign C. A Cole-Cole dipolar relaxation was also ascertained apparently due to oxygen vacancies induced dipoles. After thermal annealing the films in an oxygen atmosphere at a temperature above T{sub pol}, the aforementioned polarized state is suppressed, associated with a drastic oxygen vacancies reduction emerging from annealing process.« less

Presynaptic muscarinic control of glutamatergic synaptic transmission.

PubMed

Buño, W; Cabezas, C; Fernández de Sevilla, D

2006-01-01

The hippocampus receives cholinergic projections from the medial septal nucleus and Broca's diagonal band that terminate in the CA1, CA3, and dentate gyrus regions (Frotscher and Leranth, 1985). Glutamatergic synapses between CA3 and CA1 pyramidal neurons are presynaptically inhibited by acetylcholine (ACh), via activation of muscarinic ACh receptors (mAChRs) at the terminals of Schaffer collaterals (SCs) (Hounsgaard, 1978; Fernández de Sevilla et al., 2002, 2003). There are two types of SC-CA1 pyramidal neuron synapses. One type, called functional synapse, shows postsynaptic alpha- amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)-receptor mediated currents at resting potential (Vm) and both AMPA and N-methyl-D-aspartate receptor (NMDAR)-mediated currents when depolarized. The other type, termed silent synapse, only displays postsynaptic NMDAR-mediated currents at depolarized Vms, but does not respond at the resting Vm (Isaac et al., 1995). Using hippocampal slices obtained from young Wistar rats, we examined the effects of activation of cholinergic afferents at the stratum oriens/alveus on excitatory postsynaptic currents (EPSCs) evoked in CA1 pyramidal neurons by stimulation of SCs. We also tested the action of the nonhydrolyzable cholinergic agonist carbamylcholine chloride (CCh) on EPSCs evoked by minimal stimulation of SCs (which activates a single or very few synapses) in functional and silent synapses.

Changes in Inward Rectifier K+ Channels in Hepatic Stellate Cells During Primary Culture

PubMed Central

Lee, Dong Hyeon; Kong, In Deok; Lee, Joong-Woo

2008-01-01

Purpose This study examined the expression and function of inward rectifier K+ channels in cultured rat hepatic stellate cells (HSC). Materials and Methods The expression of inward rectifier K+ channels was measured using real-time RT-PCR, and electrophysiological properties were determined using the gramicidin-perforated patch-clamp technique. Results The dominant inward rectifier K+ channel subtypes were Kir2.1 and Kir6.1. These dominant K+ channel subtypes decreased significantly during the primary culture throughout activation process. HSC can be classified into two subgroups: one with an inward-rectifying K+ current (type 1) and the other without (type 2). The inward current was blocked by Ba2+ (100 µM) and enhanced by high K+ (140 mM), more prominently in type 1 HSC. There was a correlation between the amplitude of the Ba2+-sensitive current and the membrane potential. In addition, Ba2+ (300 µM) depolarized the membrane potential. After the culture period, the amplitude of the inward current decreased and the membrane potential became depolarized. Conclusion HSC express inward rectifier K+ channels, which physiologically regulate membrane potential and decrease during the activation process. These results will potentially help determine properties of the inward rectifier K+ channels in HSC as well as their roles in the activation process. PMID:18581597

Differential state-dependent modification of rat Na{sub v}1.6 sodium channels expressed in human embryonic kidney (HEK293) cells by the pyrethroid insecticides tefluthrin and deltamethrin

DOE Office of Scientific and Technical Information (OSTI.GOV)

He, Bingjun; Soderlund, David M., E-mail: dms6@cornell.edu

2011-12-15

We expressed rat Na{sub v}1.6 sodium channels in combination with the rat {beta}1 and {beta}2 auxiliary subunits in human embryonic kidney (HEK293) cells and evaluated the effects of the pyrethroid insecticides tefluthrin and deltamethrin on expressed sodium currents using the whole-cell patch clamp technique. Both pyrethroids produced concentration-dependent, resting modification of Na{sub v}1.6 channels, prolonging the kinetics of channel inactivation and deactivation to produce persistent 'late' currents during depolarization and tail currents following repolarization. Both pyrethroids also produced concentration dependent hyperpolarizing shifts in the voltage dependence of channel activation and steady-state inactivation. Maximal shifts in activation, determined from the voltagemore » dependence of the pyrethroid-induced late and tail currents, were {approx} 25 mV for tefluthrin and {approx} 20 mV for deltamethrin. The highest attainable concentrations of these compounds also caused shifts of {approx} 5-10 mV in the voltage dependence of steady-state inactivation. In addition to their effects on the voltage dependence of inactivation, both compounds caused concentration-dependent increases in the fraction of sodium current that was resistant to inactivation following strong depolarizing prepulses. We assessed the use-dependent effects of tefluthrin and deltamethrin on Na{sub v}1.6 channels by determining the effect of trains of 1 to 100 5-ms depolarizing prepulses at frequencies of 20 or 66.7 Hz on the extent of channel modification. Repetitive depolarization at either frequency increased modification by deltamethrin by {approx} 2.3-fold but had no effect on modification by tefluthrin. Tefluthrin and deltamethrin were equally potent as modifiers of Na{sub v}1.6 channels in HEK293 cells using the conditions producing maximal modification as the basis for comparison. These findings show that the actions of tefluthrin and deltamethrin of Na{sub v}1.6 channels in HEK293 cells differ from the effects of these compounds on Na{sub v}1.6 channels in Xenopus oocytes and more closely reflect the actions of pyrethroids on channels in their native neuronal environment. -- Highlights: Black-Right-Pointing-Pointer We expressed rat Na{sub v}1.6 voltage-gated sodium channels in HEK293 cells. Black-Right-Pointing-Pointer Tefluthrin and deltamethrin caused resting modification of Na{sub v}1.6 channels. Black-Right-Pointing-Pointer Only deltamethrin exhibited use-dependent enhancement of modification. Black-Right-Pointing-Pointer State-dependent effects of pyrethroids are influenced by the cellular context. Black-Right-Pointing-Pointer Channels in HEK293 cells exhibit properties similar to native neuronal channels.« less

The continuum of spreading depolarizations in acute cortical lesion development: Examining Leão’s legacy

PubMed Central

Shuttleworth, C William; Kirov, Sergei A; Ayata, Cenk; Hinzman, Jason M; Foreman, Brandon; Andrew, R David; Boutelle, Martyn G; Brennan, KC; Carlson, Andrew P; Dahlem, Markus A; Drenckhahn, Christoph; Dohmen, Christian; Fabricius, Martin; Farkas, Eszter; Feuerstein, Delphine; Graf, Rudolf; Helbok, Raimund; Lauritzen, Martin; Major, Sebastian; Oliveira-Ferreira, Ana I; Richter, Frank; Rosenthal, Eric S; Sakowitz, Oliver W; Sánchez-Porras, Renán; Santos, Edgar; Schöll, Michael; Strong, Anthony J; Urbach, Anja; Westover, M Brandon; Winkler, Maren KL; Witte, Otto W; Woitzik, Johannes; Dreier, Jens P

2016-01-01

A modern understanding of how cerebral cortical lesions develop after acute brain injury is based on Aristides Leão’s historic discoveries of spreading depression and asphyxial/anoxic depolarization. Treated as separate entities for decades, we now appreciate that these events define a continuum of spreading mass depolarizations, a concept that is central to understanding their pathologic effects. Within minutes of acute severe ischemia, the onset of persistent depolarization triggers the breakdown of ion homeostasis and development of cytotoxic edema. These persistent changes are diagnosed as diffusion restriction in magnetic resonance imaging and define the ischemic core. In delayed lesion growth, transient spreading depolarizations arise spontaneously in the ischemic penumbra and induce further persistent depolarization and excitotoxic damage, progressively expanding the ischemic core. The causal role of these waves in lesion development has been proven by real-time monitoring of electrophysiology, blood flow, and cytotoxic edema. The spreading depolarization continuum further applies to other models of acute cortical lesions, suggesting that it is a universal principle of cortical lesion development. These pathophysiologic concepts establish a working hypothesis for translation to human disease, where complex patterns of depolarizations are observed in acute brain injury and appear to mediate and signal ongoing secondary damage. PMID:27328690

Irreversible modification of sodium channel inactivation in toad myelinated nerve fibres by the oxidant chloramine-T.

PubMed Central

Wang, G K

1984-01-01

The effects of externally applied chloramine-T on the excitability of single toad myelinated nerve fibres were studied. Chloramine-T is a mild oxidant which reacts specifically with the cysteine and methionine residues of proteins. Chloramine-T prolongs the action potential of a single myelinated fibre by more than 1000-fold. This effect is concentration- and time-dependent; higher concentrations and longer incubation times increase prolongation. Under voltage-clamp conditions, sodium channel inactivation is markedly inhibited by chloramine-T while sodium channel activation remains normal. Prolonged depolarization of the membrane leads to a maintained sodium current. The maintained sodium currents show activation kinetics, dependence on membrane potential, and reversal potentials which are similar to those of normal, inactivating sodium currents in untreated fibres. Both the maintained and the peak sodium currents are equally inhibited by tetrodotoxin. After partial removal of sodium inactivation by brief exposures to chloramine-T, the voltage dependence of the steady-state sodium current inactivation (h infinity) is shifted in the depolarized direction by about 20 mV, even after correction for the non-inactivating component contributed by the maintained current. The phenomena described here imply that cysteine or methionine residues are critical for the sodium channel inactivation processes. The two different modifications of inactivation, its removal shown by the maintained current, and the shift in the voltage-dependence of the remaining inactivatable channels, reveal that at least two separate residues are modified by chloramine-T. PMID:6321714

Potassium currents and conductance. Comparison between motor and sensory myelinated fibers.

PubMed Central

Palti, Y; Moran, N; Stämpfli, R

1980-01-01

The potassium conductance system of sensory and motor fibers from the frog Rana esculenta were studied and compared by means of the voltage clamp. The potassium ion accumulation was first estimated from the currents and reversal potentials within the framework of both a three-compartment model and diffusion-in-an-unstirred-layer model. The potassium conductance parameters were then computed using the measured currents and corrected ionic driving forces. It was found that the potassium accumulation is faster and more pronounced in sensory fibers, the voltage dependency of the potassium conductance is steeper in sensory fibers, the maximal potassium conductance, corrected for accumulation, is approximately 1.1 S/cm2 in sensory and 0.55 S/cm2 in motor fibers, and that the conductance time constants, tau n, are smaller in sensory than in motor fibers. These differences, which increase progressively with depolarization, are not detectable for depolarization of 50 mV or smaller. The interpretation of these findings in terms of different types of potassium channels as well as their implications with regard to the differences between the excitability phenomena in motor and sensory fibers are discussed. PMID:6973371

Structural evidence that botulinum toxin blocks neuromuscular transmission by impairing the calcium influx that normally accompanies nerve depolarization

PubMed Central

1981-01-01

Taking advantage of the fact that nerve terminal mitochondria swell and sequester calcium during repetitive nerve stimulation, we here confirm that this change is caused by calcium influx into the nerve and use this fact to show that botulinum toxin abolishes such calcium influx. The optimal paradigm for producing the mitochondrial changes in normal nerves worked out to be 5 min of stimulation at 25 Hz in frog Ringer's solution containing five time more calcium than normal. Applying this same stimulation paradigm to botulinum-intoxicated nerves produced no mitochondrial changes at all. Only when intoxicated nerves were stimulated in 4-aminopyridine (which grossly exaggerates calcium currents in normal nerves) or when they were soaked in black widow spider venom (which is a nerve-specific calcium ionophore) could nerve mitochondria be induced to swell and accumulate calcium. These results indicate that nerve mitochondria are not damaged directly by the toxin and point instead to a primary inhibition of the normal depolarization- evoked calcium currents that accompany nerve activity. Because these currents normally provide the calcium that triggers transmitter secretion from the nerve, this demonstration of their inhibition helps to explain how botulinum toxin paralyzes. PMID:6259176

Remote sensing of crop parameters with a polarized, frequency-doubled Nd:YAG laser

NASA Astrophysics Data System (ADS)

Kalshoven, James E., Jr.; Tierney, Michael R., Jr.; Daughtry, Craig S. T.; McMurtrey, James E., III

1995-05-01

Polarized laser remote-sensing measurements that correlate the yield, the normalized difference vegetation index, and the leaf area index with the depolarized backscattered radiation from corn plots grown with eight different nitrogen fertilization dosages are presented. A polarized Nd:YAG laser emitting at 1064 and 532 nm is used. Depolarization increased significantly with increasing fertilization at the infrared wavelength, and there was a decrease in the depolarization at the green wavelength. The depolarization spectral difference index, defined as the absolute difference in the depolarization at the two wavelengths, is introduced as a parameter that is an indicator of the condition of the internal leaf structure.

Implementation of an Integrated, Portable Transformer Condition Monitoring Instrument in the Classroom and On-Site

ERIC Educational Resources Information Center

Chatterjee, B.; Dey, D.; Chakravorti, S.

2010-01-01

The development of integrated, portable, transformer condition monitoring (TCM) equipment for classroom demonstrations as well as for student exercises conducted in the field is discussed. Demonstrations include experimentation with real-world transformers to illustrate concepts such as polarization and depolarization current through oil-paper…

Depolarization of the Electrogenic Transmembrane Electropotential of Zea mays L. by Bipolaris (Helminthosporium) maydis Race T Toxin, Azide, Cyanide, Dodecyl Succinic Acid, or Cold Temperature 1

PubMed Central

Mertz, Stuart M.; Arntzen, Charles J.

1978-01-01

The transmembrane electrical potential of root cells of Zea mays L. cv. W64A in a modified 1× Higinbotham solution was partially depolarized by semipurified toxin obtained from Bipolaris (Helminthosporium) maydis race T. At a given toxin concentration depolarization of Texas cytoplasm cells was much greater than for normal cytoplasm cells. This observation correlated directly to the differential host susceptibility to the fungus. The time course and magnitude of depolarization were dependent on toxin concentration; at high concentration the electropotential difference change was rapid. Cortex cells depolarized more slowly than epidermal cells indicating that the toxin slowly permeated intercellular regions. Toxin concentrations which affected electropotential difference were of the same magnitude as those required to inhibit root growth, ion uptake, and mitochondrial processes. Azide, cyanide, and cold temperature (5 C) gave the same partial depolarization as did the toxin. Dodecyl succinic acid caused complete depolarization. These and other data indicate that one of the primary actions of the toxin is to inhibit electrogenic ion pumps in the plasmalemma. PMID:16660605

Activation of cathepsin L contributes to the irreversible depolarization induced by oxygen and glucose deprivation in rat hippocampal CA1 neurons.

PubMed

Kikuta, Shogo; Murai, Yoshinaka; Tanaka, Eiichiro

2017-01-01

Oxygen and glucose deprivation (OGD) elicits a rapid and irreversible depolarization with a latency of ∼5min in intracellular recordings of hippocampal CA1 neurons in rat slice preparations. In the present study, we examined the role of cathepsin L in the OGD-induced depolarization. OGD-induced depolarizations were irreversible as no recovery of membrane potential was observed. The membrane potential reached 0mV when oxygen and glucose were reintroduced immediately after the onset of the OGD-induced rapid depolarization. The OGD-induced depolarizations became reversible when the slice preparations were pre-incubated with cathepsin L inhibitors (types I and IV at 0.3-2nM and 0.3-30nM, respectively). Moreover, pre-incubation with these cathepsin inhibitors prevented the morphological changes, including swelling of the cell soma and fragmentation of dendrites, observed in control neurons after OGD. These findings suggest that the activation of cathepsin L contributes to the irreversible depolarization produced by OGD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Kilohertz and Low-Frequency Electrical Stimulation With the Same Pulse Duration Have Similar Efficiency for Inducing Isometric Knee Extension Torque and Discomfort.

PubMed

Medeiros, Flávia Vanessa; Bottaro, Martim; Vieira, Amilton; Lucas, Tiago Pires; Modesto, Karenina Arrais; Bo, Antonio Padilha L; Cipriano, Gerson; Babault, Nicolas; Durigan, João Luiz Quagliotti

2017-06-01

To test the hypotheses that, as compared with pulsed current with the same pulse duration, kilohertz frequency alternating current would not differ in terms of evoked-torque production and perceived discomfort, and as a result, it would show the same current efficiency. A repeated-measures design with 4 stimuli presented in random order was used to test 25 women: (1) 500-microsecond pulse duration, (2) 250-microsecond pulse duration, (3) 500-microsecond pulse duration and low carrier frequency (1 kHz), (4) 250-microsecond pulse duration and high carrier frequency (4 kHz). Isometric peak torque of quadriceps muscle was measured using an isokinetic dynamometer. Discomfort was measured using a visual analog scale. Currents with long pulse durations induced approximately 21% higher evoked torque than short pulse durations. In addition, currents with 500 microseconds delivered greater amounts of charge than stimulation patterns using 250-microsecond pulse durations (P < 0.05). All currents presented similar discomfort. There was no difference on stimulation efficiency with the same pulse duration. Both kilohertz frequency alternating current and pulsed current, with the same pulse duration, have similar efficiency for inducing isometric knee extension torque and discomfort. However, neuromuscular electrical stimulation (NMES) with longer pulse duration induces higher NMES-evoked torque, regardless of the carrier frequency. Pulse duration is an important variable that should receive more attention for an optimal application of NMES in clinical settings.

The proinflammatory cytokine tumor necrosis factor-α excites subfornical organ neurons.

PubMed

Simpson, Nick J; Ferguson, Alastair V

2017-09-01

Tumor necrosis factor-α (TNF-α) is a proinflammatory cytokine implicated in cardiovascular and autonomic regulation via actions in the central nervous system. TNF-α -/- mice do not develop angiotensin II (ANG II)-induced hypertension, and administration of TNF-α into the bloodstream of rats increases blood pressure and sympathetic tone. Recent studies have shown that lesion of the subfornical organ (SFO) attenuates the hypertensive and autonomic effects of TNF-α, while direct administration of TNF-α into the SFO increases blood pressure, suggesting the SFO to be a key site for the actions of TNF-α. Therefore, we used patch-clamp techniques to examine both acute and long-term effects of TNF-α on the excitability of Sprague-Dawley rat SFO neurons. It was observed that acute bath application of TNF-α depolarized SFO neurons and subsequently increased action potential firing rate. Furthermore, the magnitude of depolarization and the proportion of depolarized SFO neurons were concentration dependent. Interestingly, following 24-h incubation with TNF-α, the basal firing rate of the SFO neurons was increased and the rheobase was decreased, suggesting that TNF-α elevates SFO neuron excitability. This effect was likely mediated by the transient sodium current, as TNF-α increased the magnitude of the current and lowered its threshold of activation. In contrast, TNF-α did not appear to modulate either the delayed rectifier potassium current or the transient potassium current. These data suggest that acute and long-term TNF-α exposure elevates SFO neuron activity, providing a basis for TNF-α hypertensive and sympathetic effects. NEW & NOTEWORTHY Considerable recent evidence has suggested important links between inflammation and the pathological mechanisms underlying hypertension. The present study describes cellular mechanisms through which acute and long-term exposure of tumor necrosis factor-α (TNF-α) influences the activity of subfornical organ neurons by modulating the voltage-gated transient Na + current. This provides critical new information regarding the specific pathological mechanisms through which inflammation and TNF-α in particular may result in the development of hypertension. Copyright © 2017 the American Physiological Society.

The depolarization performances of 0.97PbZrO3-0.03Ba(Mg1/3Nb2/3)O3 ceramics under hydrostatic pressure

NASA Astrophysics Data System (ADS)

Su, Rigu; Nie, Hengchang; Liu, Zhen; Peng, Ping; Cao, Fei; Dong, Xianlin; Wang, Genshui

2018-02-01

Several 0.97PbZrO3-0.03Ba(Mg1/3Nb2/3)O3 (0.97PZ-0.03BMN) ceramics were prepared via the columbite precursor method. Their microstructures and pressure-dependent ferroelectric and depolarization performances were then studied. The X-ray diffraction patterns of ground and fresh samples indicate that a main rhombohedral symmetry crystal structure is present in the bulk and that it sits alongside a trace quantity of an orthorhombic antiferroelectric phase that results from the effect of grinding on the surface. The remanent polarization (Pr) of the 0.97PZ-0.03BMN reached 32.4 μC/cm2 at 4.5 kV/mm and ambient pressure. In an in situ pressure-induced current measurement, more than 91% of the retained Pr of the pre-poled sample was released when the pressure was increased from 194 MPa to 238 MPa. That this pressure-driven depolarization should be attributed to the pressure-induced ferroelectric-antiferroelectric phase transition is supported by the emergence of double P-E loops at high hydrostatic pressures. Moreover, the 0.97PZ-0.03BMN ceramics exhibit no temperature-induced phase transitions and little related polarization loss up to 125 °C, which suggests that Pr has excellent thermal stability. The sharp depolarization behavior at low pressures and excellent temperature stability reveal that our 0.97PZ-0.03BMN ceramics exhibit superior performances in mechanical-electrical energy conversion applications.

Nicotine inhibits potassium currents in Aplysia bag cell neurons

PubMed Central

White, Sean H.; Sturgeon, Raymond M.

2016-01-01

Acetylcholine and the archetypal cholinergic agonist, nicotine, are typically associated with the opening of ionotropic receptors. In the bag cell neurons, which govern the reproductive behavior of the marine snail, Aplysia californica, there are two cholinergic responses: a relatively large acetylcholine-induced current and a relatively small nicotine-induced current. Both currents are readily apparent at resting membrane potential and result from the opening of distinct ionotropic receptors. We now report a separate current response elicited by applying nicotine to cultured bag cell neurons under whole cell voltage-clamp. This current was ostensibly inward, best resolved at depolarized voltages, presented a noncooperative dose-response with a half-maximal concentration near 1.5 mM, and associated with a decrease in membrane conductance. The unique nicotine-evoked response was not altered by intracellular perfusion with the G protein blocker GDPβS or exposure to classical nicotinic antagonists but was occluded by replacing intracellular K+ with Cs+. Consistent with an underlying mechanism of direct inhibition of one or more K+ channels, nicotine was found to rapidly reduce the fast-inactivating A-type K+ current as well as both components of the delayed-rectifier K+ current. Finally, nicotine increased bag cell neuron excitability, which manifested as reduction in spike threshold, greater action potential height and width, and markedly more spiking to continuous depolarizing current injection. In contrast to conventional transient activation of nicotinic ionotropic receptors, block of K+ channels could represent a nonstandard means for nicotine to profoundly alter the electrical properties of neurons over prolonged periods of time. PMID:26864763

Regulation of voltage-gated Ca(2+) currents by Ca(2+)/calmodulin-dependent protein kinase II in resting sensory neurons.

PubMed

Kostic, Sandra; Pan, Bin; Guo, Yuan; Yu, Hongwei; Sapunar, Damir; Kwok, Wai-Meng; Hudmon, Andy; Wu, Hsiang-En; Hogan, Quinn H

2014-09-01

Calcium/calmodulin-dependent protein kinase II (CaMKII) is recognized as a key element in encoding depolarization activity of excitable cells into facilitated voltage-gated Ca(2+) channel (VGCC) function. Less is known about the participation of CaMKII in regulating VGCCs in resting cells. We examined constitutive CaMKII control of Ca(2+) currents in peripheral sensory neurons acutely isolated from dorsal root ganglia (DRGs) of adult rats. The small molecule CaMKII inhibitor KN-93 (1.0μM) reduced depolarization-induced ICa by 16-30% in excess of the effects produced by the inactive homolog KN-92. The specificity of CaMKII inhibition on VGCC function was shown by the efficacy of the selective CaMKII blocking peptide autocamtide-2-related inhibitory peptide in a membrane-permeable myristoylated form, which also reduced VGCC current in resting neurons. Loss of VGCC currents is primarily due to reduced N-type current, as application of mAIP selectively reduced N-type current by approximately 30%, and prior N-type current inhibition eliminated the effect of mAIP on VGCCs, while prior block of L-type channels did not reduce the effect of mAIP on total ICa. T-type currents were not affected by mAIP in resting DRG neurons. Transduction of sensory neurons in vivo by DRG injection of an adeno-associated virus expressing AIP also resulted in a loss of N-type currents. Together, these findings reveal a novel molecular adaptation whereby sensory neurons retain CaMKII support of VGCCs despite remaining quiescent. Published by Elsevier Inc.

The sea anemone toxin AdE-1 modifies both sodium and potassium currents of rat cardiomyocytes.

PubMed

Nesher, Nir; Zlotkin, Eliahu; Hochner, Binyamin

2014-07-01

AdE-1, a cardiotonic peptide recently isolated from the sea anemone Aiptasia diaphana, contains 44 amino acids and has a molecular mass of 4907 Da. It was previously found to resemble other sea anemone type 1 and 2 Na+ channel toxins, enhancing contractions of rat cardiomyocytes and slowing their twitch relaxation; however, it did not induce spontaneous twitches. AdE-1 increased the duration of the cardiomyocyte action potential and decreased its amplitude and its time-to-peak in a concentration-dependent manner, without affecting its threshold and cell resting potential. Nor did it generate the early and delayed after-depolarizations characteristic of sea anemone Na+ channel toxins. To further understand its mechanism of action we investigated the effect of AdE-1 on the major ion currents of rat cardiomyocytes. In the present study we show that AdE-1 markedly slowed inactivation of the Na+ current, enhancing and prolonging the current influx with no effect on current activation, possibly through direct interaction with the site 3 receptor of the Na+ channel. No significant effect of AdE-1 on the Ca2+ current was observed, but, unexpectedly, AdE-1 significantly increased the amplitude of the transient component of the K+ current, shifting the current threshold to more negative membrane potentials. This effect on the K+ current has not been found in any other sea anemone toxin and may explain the exclusive reduction in action potential amplitude and the absence of the action potential disorders found with other toxins, such as early and delayed after-depolarizations.

Voltage-dependent inward currents in smooth muscle cells of skeletal muscle arterioles

PubMed Central

Shirokov, Roman E.

2018-01-01

Voltage-dependent inward currents responsible for the depolarizing phase of action potentials were characterized in smooth muscle cells of 4th order arterioles in mouse skeletal muscle. Currents through L-type Ca2+ channels were expected to be dominant; however, action potentials were not eliminated in nominally Ca2+-free bathing solution or by addition of L-type Ca2+ channel blocker nifedipine (10 μM). Instead, Na+ channel blocker tetrodotoxin (TTX, 1 μM) reduced the maximal velocity of the upstroke at low, but not at normal (2 mM), Ca2+ in the bath. The magnitude of TTX-sensitive currents recorded with 140 mM Na+ was about 20 pA/pF. TTX-sensitive currents decreased five-fold when Ca2+ increased from 2 to 10 mM. The currents reduced three-fold in the presence of 10 mM caffeine, but remained unaltered by 1 mM of isobutylmethylxanthine (IBMX). In addition to L-type Ca2+ currents (15 pA/pF in 20 mM Ca2+), we also found Ca2+ currents that are resistant to 10 μM nifedipine (5 pA/pF in 20 mM Ca2+). Based on their biophysical properties, these Ca2+ currents are likely to be through voltage-gated T-type Ca2+ channels. Our results suggest that Na+ and at least two types (T- and L-) of Ca2+ voltage-gated channels contribute to depolarization of smooth muscle cells in skeletal muscle arterioles. Voltage-gated Na+ channels appear to be under a tight control by Ca2+ signaling. PMID:29694371

The interplay of seven subthreshold conductances controls the resting membrane potential and the oscillatory behavior of thalamocortical neurons

PubMed Central

Zagha, Edward; Mato, German; Rudy, Bernardo; Nadal, Marcela S.

2014-01-01

The signaling properties of thalamocortical (TC) neurons depend on the diversity of ion conductance mechanisms that underlie their rich membrane behavior at subthreshold potentials. Using patch-clamp recordings of TC neurons in brain slices from mice and a realistic conductance-based computational model, we characterized seven subthreshold ion currents of TC neurons and quantified their individual contributions to the total steady-state conductance at levels below tonic firing threshold. We then used the TC neuron model to show that the resting membrane potential results from the interplay of several inward and outward currents over a background provided by the potassium and sodium leak currents. The steady-state conductances of depolarizing Ih (hyperpolarization-activated cationic current), IT (low-threshold calcium current), and INaP (persistent sodium current) move the membrane potential away from the reversal potential of the leak conductances. This depolarization is counteracted in turn by the hyperpolarizing steady-state current of IA (fast transient A-type potassium current) and IKir (inwardly rectifying potassium current). Using the computational model, we have shown that single parameter variations compatible with physiological or pathological modulation promote burst firing periodicity. The balance between three amplifying variables (activation of IT, activation of INaP, and activation of IKir) and three recovering variables (inactivation of IT, activation of IA, and activation of Ih) determines the propensity, or lack thereof, of repetitive burst firing of TC neurons. We also have determined the specific roles that each of these variables have during the intrinsic oscillation. PMID:24760784

Activation of Ih and TTX-sensitive sodium current at subthreshold voltages during CA1 pyramidal neuron firing

PubMed Central

Yamada-Hanff, Jason

2015-01-01

We used dynamic clamp and action potential clamp techniques to explore how currents carried by tetrodotoxin-sensitive sodium channels and HCN channels (Ih) regulate the behavior of CA1 pyramidal neurons at resting and subthreshold voltages. Recording from rat CA1 pyramidal neurons in hippocampal slices, we found that the apparent input resistance and membrane time constant were strongly affected by both conductances, with Ih acting to decrease apparent input resistance and time constant and sodium current acting to increase both. We found that both Ih and sodium current were active during subthreshold summation of artificial excitatory postsynaptic potentials (EPSPs) generated by dynamic clamp, with Ih dominating at less depolarized voltages and sodium current at more depolarized voltages. Subthreshold sodium current—which amplifies EPSPs—was most effectively recruited by rapid voltage changes, while Ih—which blunts EPSPs—was maximal for slow voltage changes. The combined effect is to selectively amplify rapid EPSPs. We did similar experiments in mouse CA1 pyramidal neurons, doing voltage-clamp experiments using experimental records of action potential firing of CA1 neurons previously recorded in awake, behaving animals as command voltages to quantify flow of Ih and sodium current at subthreshold voltages. Subthreshold sodium current was larger and subthreshold Ih was smaller in mouse neurons than in rat neurons. Overall, the results show opposing effects of subthreshold sodium current and Ih in regulating subthreshold behavior of CA1 neurons, with subthreshold sodium current prominent in both rat and mouse CA1 pyramidal neurons and additional regulation by Ih in rat neurons. PMID:26289465

Nanomolar Oxytocin Synergizes with Weak Electrical Afferent Stimulation to Activate the Locomotor CPG of the Rat Spinal Cord In Vitro

PubMed Central

Dose, Francesco; Zanon, Patrizia; Coslovich, Tamara; Taccola, Giuliano

2014-01-01

Synergizing the effect of afferent fibre stimulation with pharmacological interventions is a desirable goal to trigger spinal locomotor activity, especially after injury. Thus, to better understand the mechanisms to optimize this process, we studied the role of the neuropeptide oxytocin (previously shown to stimulate locomotor networks) on network and motoneuron properties using the isolated neonatal rat spinal cord. On motoneurons oxytocin (1 nM–1 μM) generated sporadic bursts with superimposed firing and dose-dependent depolarization. No desensitization was observed despite repeated applications. Tetrodotoxin completely blocked the effects of oxytocin, demonstrating the network origin of the responses. Recording motoneuron pool activity from lumbar ventral roots showed oxytocin mediated depolarization with synchronous bursts, and depression of reflex responses in a stimulus and peptide-concentration dependent fashion. Disinhibited bursting caused by strychnine and bicuculline was accelerated by oxytocin whose action was blocked by the oxytocin antagonist atosiban. Fictive locomotion appeared when subthreshold concentrations of NMDA plus 5HT were coapplied with oxytocin, an effect prevented after 24 h incubation with the inhibitor of 5HT synthesis, PCPA. When fictive locomotion was fully manifested, oxytocin did not change periodicity, although cycle amplitude became smaller. A novel protocol of electrical stimulation based on noisy waveforms and applied to one dorsal root evoked stereotypic fictive locomotion. Whenever the stimulus intensity was subthreshold, low doses of oxytocin triggered fictive locomotion although oxytocin per se did not affect primary afferent depolarization evoked by dorsal root pulses. Among the several functional targets for the action of oxytocin at lumbar spinal cord level, the present results highlight how small concentrations of this peptide could bring spinal networks to threshold for fictive locomotion in combination with other protocols, and delineate the use of oxytocin to strengthen the efficiency of electrical stimulation to activate locomotor circuits. PMID:24658101

Dual amplitude pulse generator for radiation detectors

DOEpatents

Hoggan, Jerry M.; Kynaston, Ronnie L.; Johnson, Larry O.

2001-01-01

A pulsing circuit for producing an output signal having a high amplitude pulse and a low amplitude pulse may comprise a current source for providing a high current signal and a low current signal. A gate circuit connected to the current source includes a trigger signal input that is responsive to a first trigger signal and a second trigger signal. The first trigger signal causes the gate circuit to connect the high current signal to a pulse output terminal whereas the second trigger signal causes the gate circuit to connect the low current signal to the pulse output terminal.

Methods and apparatus for using gas and liquid phase cathodic depolarizers

NASA Technical Reports Server (NTRS)

Murphy, Oliver J. (Inventor); Hitchens, G. Duncan (Inventor)

1998-01-01

The invention provides methods for using gas and liquid phase cathodic depolarizers in an electrochemical cell having a cation exchange membrane in intimate contact with the anode and cathode. The electrochemical conversion of cathodic depolarizers at the cathode lowers the cell potential necessary to achieve a desired electrochemical conversion, such as ozone evolution, at the anode. When gaseous cathodic depolarizers, such as oxygen, are used, a gas diffusion cathode having the cation exchange membrane bonded thereto is preferred. When liquid phase cathodic depolarizers are used, the cathode may be a flow-by electrode, flow-through electrode, packed-bed electrode or a fluidized-bed electrode in intimate contact with the cation exchange membrane.

Mechanisms and roles of muscarinic activation in guinea-pig adrenal medullary cells

PubMed Central

Harada, Keita; Matsuoka, Hidetada; Nakamura, Jun; Warashina, Akira

2012-01-01

Muscarinic receptors are expressed in the adrenal medullary (AM) cells of various mammals, but their physiological roles are controversial. Therefore, the ionic mechanism for muscarinic receptor-mediated depolarization and the role of muscarinic receptors in neuronal transmission were investigated in dissociated guinea-pig AM cells and in the perfused guinea-pig adrenal gland. Bath application of muscarine induced an inward current at −60 mV. This inward current was partially suppressed by quinine with an IC50 of 6.1 μM. The quinine-insensitive component of muscarine-induced currents changed the polarity at −78 mV and was inhibited by bupivacaine, a TWIK-related acid-sensitive K+ (TASK) channel inhibitor. Conversely, the current-voltage relationship for the bupivacaine-insensitive component of muscarine currents showed a reversal potential of −5 mV and a negative slope below −40 mV. External application of La3+ had a double action on muscarine currents of both enhancement and suppression. Immunoblotting and immunocytochemistry revealed expression of TASK1 channels and cononical transient receptor potential channels 1, 4, 5, and 7 in guinea-pig AM cells. Retrograde application of atropine reversibly suppressed transsynaptically evoked catecholamine secretion from the adrenal gland. The results indicate that muscarinic receptor stimulation in guinea-pig AM cells induces depolarization through inhibition of TASK channels and activation of nonselective cation channels and that muscarinic receptors are involved in neuronal transmission from the splanchnic nerve. PMID:22744007

N-type Ca2+ channels mediate transmitter release at the electromotoneuron-electrocyte synapses of the weakly electric fish Gymnotus carapo.

PubMed

Sierra, F; Lorenzo, D; Macadar, O; Buño, W

1995-06-19

The effects of omega-conotoxin-GVIA (omega-CgTX) on synaptic transmission were studied in the electromotoneuron-electrocyte synapses of the electric organ (EO) of the weakly electric fish Gymnotus carapo. omega-CgTX selectively and irreversibly blocked excitatory postsynaptic potentials (EPSPs) in a dose dependent-manner. The toxin had no effect on: (a) resting postsynaptic membrane potential and conductance; (b) postsynaptic action potentials elicited by depolarizing transmembrane current pulses; (c) the action potential conduction in the presynaptic fiber; (d) acetylcholine (ACh)-induced postsynaptic responses. Nifedipine - a selective dihydropyridine antagonist of the L-type voltage-dependent Ca2+ channels (VDCCs) - did not affect synaptic transmission. Transmission was also undisturbed by the peptide omega-Agatoxin (omega-Aga-IVA), the low molecular weight polyamine, funnel-web toxin (FTX) - both included in the venom of the spider Agelenopsis aperta - and its synthetic analog sFTX, all selective blockers of P-type VDCCs. Since omega-CgTX irreversibly blocks the N-type VDCCs, we conclude that presynaptic N-type VDCCs mediate transmitter release at electromotoneuron terminals. The VDCCs involved in fish peripheral electromotoneuron-electrocyte presynaptic transmitter release are therefore similar to those in amphibian, reptilian and avian peripheral synapses, but differ from mammalian and invertebrate motoneuron terminals.

Cardiac torsion and electromagnetic fields: the cardiac bioinformation hypothesis.

PubMed

Burleson, Katharine O; Schwartz, Gary E

2005-01-01

Although in physiology the heart is often referred to as a simple piston pump, there are in fact two additional features that are integral to cardiac physiology and function. First, the heart as it contracts in systole, also rotates and produces torsion due to the structure of the myocardium. Second, the heart produces a significant electromagnetic field with each contraction due to the coordinated depolarization of myocytes producing a current flow. Unlike the electrocardiogram, the magnetic field is not limited to volume conduction and extends outside the body. The therapeutic potential for interaction of this cardioelectromagnetic field both within and outside the body is largely unexplored. It is our hypothesis that the heart functions as a generator of bioinformation that is central to normative functioning of body. The source of this bioinformation is based on: (1) vortex blood flow in the left ventricle; (2) a cardiac electromagnetic field and both; (3) heart sounds; and (4) pulse pressure which produce frequency and amplitude information. Thus, there is a multidimensional role for the heart in physiology and biopsychosocial dynamics. Recognition of these cardiac properties may result in significant implications for new therapies for cardiovascular disease based on increasing cardiac energy efficiency (coherence) and bioinformation from the cardioelectromagnetic field. Research studies to test this hypothesis are suggested.

Impact induced depolarization of ferroelectric materials

NASA Astrophysics Data System (ADS)

Agrawal, Vinamra; Bhattacharya, Kaushik

2018-06-01

We study the large deformation dynamic behavior and the associated nonlinear electro-thermo-mechanical coupling exhibited by ferroelectric materials in adiabatic environments. This is motivated by a ferroelectric generator which involves pulsed power generation by loading the ferroelectric material with a shock, either by impact or a blast. Upon impact, a shock wave travels through the material inducing a ferroelectric to nonpolar phase transition giving rise to a large voltage difference in an open circuit situation or a large current in a closed circuit situation. In the first part of this paper, we provide a general continuum mechanical treatment of the situation assuming a sharp phase boundary that is possibly charged. We derive the governing laws, as well as the driving force acting on the phase boundary. In the second part, we use the derived equations and a particular constitutive relation that describes the ferroelectric to nonpolar phase transition to study a uniaxial plate impact problem. We develop a numerical method where the phase boundary is tracked but other discontinuities are captured using a finite volume method. We compare our results with experimental observations to find good agreement. Specifically, our model reproduces the observed exponential rise of charge as well as the resistance dependent Hugoniot. We conclude with a parameter study that provides detailed insight into various aspects of the problem.

Source of polarised deuterons. (JINR accelerator complex)

NASA Astrophysics Data System (ADS)

Fimushkin, V. V.; Belov, A. S.; Kovalenko, A. D.; Kutuzova, L. V.; Prokofichev, Yu. V.; Shimanskiy, S. S.; Vadeev, V. P.

2008-08-01

The proposed project assumes the development of a universal high-intensity source of polarized deuterons (protons) using a charge-exchange plasma ionizer. The design output current of the source will be up to 10mA for ↑ D+(↑ H+) and polarization will be up to 90% of the maximal vector (±1) and tensor (+1,-2) polarization. The project is based on the equipment which was supplied within the framework of an agreement between JINR and IUCF (Bloomington, USA). The project will be realized in close cooperation with INR (Moscow, Russia). The source will be installed in the linac hall (LU-20) and polarization of beams will be measured at the output of LU-20. The main purpose of the project is to increase the intensity of the accelerated polarized beams at the JINR Accelerator Complex up to 1010 d/pulse. Calculations and first accelerator runs have shown that the depolarization resonances are absent for the deuteron beam in the entire energy range of the NUCLOTRON. The source could be transformed into a source of polarized negative ions if necessary. The period of reliable operation without participation of the personnel should be within 1000 hours. The project should be implemented within two to two and a half years from the start of funding.

A depolarization and attenuation experiment using the CTS satellite. Volume 1: Experiment description

NASA Technical Reports Server (NTRS)

Bostian, C. W.; Holt, S. B., Jr.; Kauffman, S. R.; Manus, E. A.; Marshall, R. E.; Stutzman, W. L.; Wiley, P. H.

1976-01-01

An experiment for measuring precipitation attenuation and depolarization on the Communications Technology Satellite (CTS) 11.7 GHz downlink is described. Attenuation and depolarization of the signal received from the spacecraft is monitored on a 24 hour basis. Data is correlated with ground weather conditions. Theoretical models for millimeter wave propagation through rain are refined for maximum agreement with observed data. Techniques are developed for predicting and mimimizing the effects of rain scatter and depolarization on future satellite communication systems.

Depolarization measurements on the ATS-6 20 GHz downlink A description of the VPI&SU experiment and some initial results. [meteorological precipitation effects

NASA Technical Reports Server (NTRS)

Bostian, C. W.; Stutzman, W. L.; Manus, E. A.; Wiley, P. H.; Marshall, R. E.

1975-01-01

The experiment considered is mainly concerned with the depolarizing effects of precipitation at millimeter wavelengths. Excessive depolarization introduces cross talk into communication systems which employ orthogonal polarization for frequency reuse. An understanding of atmospheric depolarization phenomena is, therefore, required for the design of future earth-satellite communications systems. Attenuation and cross polarization ratio data obtained under various meteorological conditions, including rain and a snowstorm, are presented.

Results of the VPI&SU Comstar experiment. [depolarization and attenuation due to rain

NASA Technical Reports Server (NTRS)

Andrews, J. H.; Ozbay, C.; Pratt, T.; Bostian, C. W.; Manus, E. A.; Gaines, J. M.; Marshall, R. E.; Stutzman, W. L.; Wiley, P. H.

1982-01-01

This paper summarizes annual and cumulative attenuation data, depolarization data, and associated local rain rate distributions obtained with the Comstar family of 19.04- and 28.56-GHz satellite beacons during the years 1977-1981. It discusses the relationships between attenuation and rain rate and between attenuation and depolarization, compares measured data on the joint distribution of attenuation and depolarization, and examines the limitations that propagation effects will impose on future 20/30-GHz satellite communications systems.

Aerosol Classification from High Spectral Resolution Lidar Measurements

NASA Astrophysics Data System (ADS)

Burton, S. P.; Hair, J. W.; Ferrare, R. A.; Hostetler, C. A.; Kahnert, M.; Vaughan, M. A.; Cook, A. L.; Harper, D. B.; Berkoff, T.; Seaman, S. T.; Collins, J. E., Jr.; Fenn, M. A.; Rogers, R. R.

2015-12-01

The NASA Langley airborne High Spectral Resolution Lidars, HSRL-1 and HSRL-2, have acquired large datasets of vertically resolved aerosol extinction, backscatter, and depolarization during >30 airborne field missions since 2006. The lidar measurements of aerosol intensive parameters like lidar ratio and color ratio embed information about intrinsic aerosol properties, and are combined to qualitatively classify HSRL aerosol measurements into aerosol types. Knowledge of aerosol type is important for assessing aerosol radiative forcing, and can provide useful information for source attribution studies. However, atmospheric aerosol is frequently not a single pure type, but instead is a mixture, which affects the optical and radiative properties of the aerosol. We show that aerosol intensive parameters measured by lidar can be understood using mixing rules for cases of external mixing. Beyond coarse classification and mixing between classes, variations in the lidar aerosol intensive parameters provide additional insight into aerosol processes and composition. This is illustrated by depolarization measurements at three wavelengths, 355 nm, 532 nm, and 1064 nm, made by HSRL-2. Particle depolarization ratio is an indicator of non-spherical particles. Three cases each have a significantly different spectral dependence of the depolarization ratio, related to the size of the depolarizing particles. For two dust cases, large non-spherical particles account for the depolarization of the lidar light. The spectral dependence reflects the size distribution of these particles and reveals differences in the transport histories of the two plumes. For a smoke case, the depolarization is inferred to be due to the presence of small coated soot aggregates. Interestingly, the depolarization at 355 nm is similar for this smoke case compared to the dust cases, having potential implications for the upcoming EarthCARE satellite, which will measure particle depolarization ratio only at 355 nm.

Tachykininergic slow depolarization of motoneurones evoked by descending fibres in the neonatal rat spinal cord.

PubMed

Kurihara, T; Yoshioka, K; Otsuka, M

1995-06-15

1. In the isolated spinal cord of the neonatal rat, repetitive electrical stimulation of the upper cervical region elicited a prolonged depolarization of lumbar motoneurones (L3-5) lasting 1-2 min, which was recorded extracellularly from ventral roots, or intracellularly. 2. This depolarizing response was markedly depressed by the excitatory amino acid receptor antagonists D-(-)-2-amino-5-phosphonovaleric acid (D-APV, 30 microM) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM). The remaining response was further depressed by a 5-hydroxytryptamine (5-HT) receptor antagonist, ketanserin (3 microM). 3. In the presence of these antagonists, a small part of the depolarizing response of slow time course remained, and this response was partially blocked by the tachykinin NK1 receptor antagonists GR71251 (0.3-5 microM) and RP67580 (0.3-1 microM). In contrast, RP68651 (0.3-1 microM), the inactive enantiomer of RP67580, had no effect on the depolarizing response. 4. The slow depolarizing response in the presence of D-APV, CNQX and ketanserin was markedly potentiated by a peptidase inhibitor, thiorphan (1 microM). 5. This descending fibre-evoked slow depolarization became smaller after prolonged treatment (5-7 h) with 5,7-dihydroxytryptamine (10 microM), a neurotoxin for 5-HT neurones. Under such conditions, the effects of thiorphan and GR71251 on the slow depolarization were virtually absent. 6. Under the action of D-APV, CNQX and ketanserin, applications of tachykinins, substance P and neurokinin A produced depolarizing responses of lumbar motoneurones, and the responses were depressed by GR71251 and potentiated by thiorphan. 7. These results suggest that tachykinins contained in serotonergic fibres serve as neurotransmitters mediating the descending fibre-evoked slow excitatory postsynaptic potentials in motoneurones.

Technology advancement of the electrochemical CO2 concentrating process

NASA Technical Reports Server (NTRS)

Schubert, F. H.; Heppner, D. B.; Hallick, T. M.; Woods, R. R.

1979-01-01

Two multicell, liquid-cooled, advanced electrochemical depolarized carbon dioxide concentrator modules were fabricated. The cells utilized advanced, lightweight, plated anode current collectors, internal liquid cooling and lightweight cell frames. Both were designed to meet the carbon dioxide removal requirements of one-person, i.e., 1.0 kg/d (2.2 lb/d).

Low temperature dielectric relaxation of poly (L-lactic acid) (PLLA) by Thermally Stimulated Depolarization Current

NASA Astrophysics Data System (ADS)

Mishra Patidar, Manju; Jain, Deepti; Nath, R.; Ganesan, V.

2016-10-01

Poly (L-lactic acid) (PLLA) is a biodegradable and biocompatible polyester that can be produced by renewable resources, like corn. Being non-toxic to human body, PLLA is used in biomedical applications, like surgical sutures, bone fixation devices, or controlled drug delivery. Besides its application studies, very few experiments have been done to study its dielectric relaxation in the low temperature region. Keeping this in mind we have performed a low temperature thermally stimulated depolarization current (TSDC) studies over the temperature range of 80K-400K to understand the relaxation phenomena of PLLA. We could observe a multi modal broad relaxation of small but significant intensity at low temperatures while a sharp and high intense peak around glass transition temperature, Tg∼ 333K, of PLLA has appeared. The fine structure of the low temperature TSDC peak may be attributed to the spherulites formation of crystallite regions inter twinned with the polymer as seen in AFM and appear to be produced due to an isothermal crystallization process. XRD analysis also confirms the semicrystalline nature of the PLLA film.

Effects of body temperature on neural activity in the hippocampus: regulation of resting membrane potentials by transient receptor potential vanilloid 4.

PubMed

Shibasaki, Koji; Suzuki, Makoto; Mizuno, Atsuko; Tominaga, Makoto

2007-02-14

Physiological body temperature is an important determinant for neural functions, and it is well established that changes in temperature have dynamic influences on hippocampal neural activities. However, the detailed molecular mechanisms have never been clarified. Here, we show that hippocampal neurons express functional transient receptor potential vanilloid 4 (TRPV4), one of the thermosensitive TRP (transient receptor potential) channels, and that TRPV4 is constitutively active at physiological temperature. Activation of TRPV4 at 37 degrees C depolarized the resting membrane potential in hippocampal neurons by allowing cation influx, which was observed in wild-type (WT) neurons, but not in TRPV4-deficient (TRPV4KO) cells, although dendritic morphology, synaptic marker clustering, and synaptic currents were indistinguishable between the two genotypes. Furthermore, current injection studies revealed that TRPV4KO neurons required larger depolarization to evoke firing, equivalent to WT neurons, indicating that TRPV4 is a key regulator for hippocampal neural excitabilities. We conclude that TRPV4 is activated by physiological temperature in hippocampal neurons and thereby controls their excitability.

Dopamine modulates an intrinsic mGluR5-mediated depolarization underlying prefrontal persistent activity

PubMed Central

Sidiropoulou, Kyriaki; Lu, Fang-Min; Fowler, Melissa A.; Xiao, Rui; Phillips, Christopher; Ozkan, Emin D.; Zhu, Michael X.; White, Francis J.; Cooper, Donald C.

2009-01-01

Intrinsic properties of neurons that enable them to maintain depolarized, persistently activated states in the absence of sustained input are poorly understood. In short-term memory tasks, individual prefrontal cortical (PFC) neurons are capable of maintaining persistent action potential output during delay periods between informative cues and behavioral responses. Dopamine and drugs of abuse alter PFC function and working memory possibly by modulating intrinsic neuronal properties. Here we use patch-clamp recording of layer 5 PFC pyramidal neurons to identify an action potential burst-evoked intrinsic mGluR5-mediated postsynaptic depolarization that initiates an activated state. Depolarization occurs in the absence of recurrent synaptic activity and is reduced by a postsynaptic dopamine D1/5 receptor pathway. The depolarization is substantially diminished following behavioral sensitization to cocaine; moreover the D1/5 receptor modulation is lost. We propose the burst-evoked intrinsic depolarization to be a novel form of short-term cellular memory that is modulated by dopamine and cocaine experience. PMID:19169252

On remote sensing of small aerosol particles with polarized light

NASA Astrophysics Data System (ADS)

Sun, W.

2012-12-01

The CALIPSO satellite mission consistently measures volume (including molecule and particulate) light depolarization ratio of ~2% for smoke, compared to ~1% for marine aerosols and ~15% for dust. The observed ~2% smoke depolarization ratio comes primarily from the nonspherical habits of particles in the smoke at certain particle sizes. The depolarization of linearly polarized light by small sphere aggregates and irregular Gaussian-shaped particles is studied, to reveal the physics between the depolarization of linearly polarized light and aerosol shape and size. It is found that randomly oriented nonspherical particles have some common depolarization properties as functions of scattering angle and size parameter. This may be very useful information for active remote sensing of small nonspherical aerosols using polarized light. We also show that the depolarization ratio from the CALIPSO measurements could be used to derive smoke aerosol particle size. The mean particle size of South-African smoke is estimated to be about half of the 532 nm wavelength of the CALIPSO lidar.

Formalin produces depolarizations in human airway smooth muscle in vitro.

PubMed

Richards, Ira S; DeHate, Robin B

2006-03-01

Respiratory irritants may result in airway smooth muscle (ASM) depolarization and bronchoconstriction. We examined the effect of formalin on membrane potentials in human ASM in two types of in vitro preparations: strip preparations, which contain functional sensory and motor nerve endings and cultured cells, which lack these nerve endings due to the tissue dissociation process. Depolarizations occurred in atropine-treated strip preparations in response to formalin exposures, but not in similarly-treated cultured cells, suggesting a role for non-cholinergic mediators in formalin-induced depolarization. It is suggested that formalin may act as an irritant to produce bronchoconstriction that is mediated by the release of endogenous substance P (SP) from peripheral sensory nerve endings. This is supported by our observation that exogenous SP produced depolarizations of a magnitude similar to those produced by formalin in both strip preparations and cultured cells. In addition, capsaicin, which releases endogenous SP from nerve endings, produced depolarizations of a magnitude similar to formalin in strip preparations, but was without effect in cultured cells.

The Slope Imaging Multi-polarization Photon-counting Lidar: an Advanced Technology Airborne Laser Altimeter

NASA Astrophysics Data System (ADS)

Dabney, P.; Harding, D. J.; Huss, T.; Valett, S.; Yu, A. W.; Zheng, Y.

2009-12-01

The Slope Imaging Multi-polarization Photon-counting Lidar (SIMPL) is an airborne laser altimeter developed through the NASA Earth Science Technology Office Instrument Incubator Program with a focus on cryopshere remote sensing. The SIMPL instrument incorporates a variety of advanced technologies in order to demonstrate measurement approaches of potential benefit for improved airborne laser swath mapping and spaceflight laser altimeter missions. SIMPL incorporates beam splitting, single-photon ranging and polarimetry technologies at green and near-infrared wavelengths in order to achieve simultaneous sampling of surface elevation, slope, roughness and scattering properties, the latter used to differentiate surface types. The transmitter is a 1 nsec pulse width, 11 kHz, 1064 nm microchip laser, frequency doubled to 532 nm and split into four plane-polarized beams using birefringent calcite crystal in order to maintain co-alignment of the two colors. The 16 channel receiver splits the received energy for each beam into the two colors and each color is split into energy parallel and perpendicular to the transmit polarization plane thereby proving a measure of backscatter depolarization. The depolarization ratio is sensitive to the proportions of specular reflection and surface and volume scattering, and is a function of wavelength. The ratio can differentiate, for example, water, young translucent ice, older granular ice and snow. The solar background count rate is controlled by spatial filtering using a pinhole array and by spectral filtering using temperature-controlled narrow bandwidth filters. The receiver is fiber coupled to 16 Single Photon Counting Modules (SPCMs). To avoid range biases due to the long dead time of these detectors the probability of detection per laser fire on each channel is controlled to be below 30%, using mechanical irises and flight altitude. Event timers with 0.1 nsec resolution in combination the narrow transmit pulse yields single photon ranging precision of 8 cm. The high speed, high throughput data system is capable of recording 22 million time-tagged photon detection events per second. At typical aircraft flight speeds, each of the 16 channels acquires a single photon range every 5 to 15 cm along the four profiles providing a highly sampled measure of surface roughness. The nominal flight altitude is 5 km yielding 10 m spacing between the four beam profiles, providing a measure of surface slope at 10 m length scales. The altitude is currently constrained by the low signal level of the NIR cross-polarized channels. SIMPL’s measurement capabilities provide information about surface elevation, roughness, slope and type of value in characterizing ice sheet surfaces and sea ice, including their melt state. Capabilities will be illustrated using data acquired over Lake Erie ice cover in February, 2009.

Direct muscarinic and nicotinic receptor-mediated excitation of rat medial vestibular nucleus neurons in vitro

NASA Technical Reports Server (NTRS)

Phelan, K. D.; Gallagher, J. P.

1992-01-01

We have utilized intracellular recording techniques to investigate the cholinoceptivity of rat medial vestibular nucleus (MVN) neurons in a submerged brain slice preparation. Exogenous application of the mixed cholinergic agonists, acetylcholine (ACh) or carbachol (CCh), produced predominantly membrane depolarization, induction of action potential firing, and decreased input resistance. Application of the selective muscarinic receptor agonist muscarine (MUSC), or the selective nicotinic receptor agonists nicotine (NIC) or 1,1-dimethyl-4-phenylpiperazinium (DMPP) also produced membrane depolarizations. The MUSC-induced depolarization was accompanied by decreased conductance, while an increase in conductance appeared to underlie the NIC- and DMPP-induced depolarizations. The muscarinic and nicotinic receptor mediated depolarizations persisted in tetrodotoxin and/or low Ca2+/high Mg2+ containing media, suggesting direct postsynaptic receptor activation. The MUSC-induced depolarization could be reversibly blocked by the selective muscarinic-receptor antagonist, atropine, while the DMPP-induced depolarization could be reversibly suppressed by the selective ganglionic nicotinic-receptor antagonist, mecamylamine. Some neurons exhibited a transient membrane hyperpolarization during the depolarizing response to CCh or MUSC application. This transient inhibition could be reversibly blocked by the gamma-aminobutyric acid (GABA) antagonist, bicuculline, suggesting that the underlying hyperpolarization results indirectly from the endogenous release of GABA acting at GABA receptors. This study confirms the cholinoceptivity of MVN neurons and establishes that individual MVN cells possess muscarinic as well as nicotinic receptors. The data provide support for a prominent role of cholinergic mechanisms in the direct and indirect regulation of the excitability of MVN neurons.

Assessment of aerosol's mass concentrations from measured linear particle depolarization ratio (vertically resolved) and simulations

NASA Astrophysics Data System (ADS)

Nemuc, A.; Vasilescu, J.; Talianu, C.; Belegante, L.; Nicolae, D.

2013-11-01

Multi-wavelength depolarization Raman lidar measurements from Magurele, Romania are used in this study along with simulated mass-extinction efficiencies to calculate the mass concentration profiles of different atmospheric components, due to their different depolarization contribution to the 532 nm backscatter coefficient. Linear particle depolarization ratio (δpart) was computed using the relative amplification factor and the system-dependent molecular depolarization. The low depolarizing component was considered as urban/smoke, with a mean δpart of 3%, while for the high depolarizing component (mineral dust) a mean δpart of 35% was assumed. For this study 11 months of lidar measurements were analysed. Two study cases are presented in details: one for a typical Saharan dust aerosol intrusion, 10 June 2012 and one for 12 July 2012 when a lofted layer consisting of biomass burning smoke extended from 3 to 4.5 km height. Optical Properties of Aerosols and Clouds software package (OPAC) classification and conversion factors were used to calculate mass concentrations. We found that calibrated depolarization measurements are critical in distinguishing between smoke-reach aerosol during the winter and dust-reach aerosol during the summer, as well as between elevated aerosol layers having different origins. Good agreement was found between lidar retrievals and DREAM- Dust REgional Atmospheric Model forecasts in cases of Saharan dust. Our method was also compared against LIRIC (The Lidar/Radiometer Inversion Code) and very small differences were observed.

Assessment of aerosol's mass concentrations from measured linear particle depolarization ratio (vertically resolved) and simulations

NASA Astrophysics Data System (ADS)

Nemuc, A.; Vasilescu, J.; Talianu, C.; Belegante, L.; Nicolae, D.

2013-06-01

Multiwavelength depolarization Raman lidar measurements from Magurele, Romania are used in this study along with simulated mass-extinction efficiencies to calculate the mass concentrations profiles of different atmospheric components, due to their different depolarization contribution to the 532 nm backscatter coefficient. Linear particle depolarization ratio (δpart) was computed using the relative amplification factor and the system-dependent molecular depolarization. The low depolarizing component was considered as urban/smoke, with a mean δpart of 3%, while for the high depolarizing component (mineral dust) a mean δpart of 35% was assumed. For this study 11 months of lidar measurements were analyzed. Two study cases are presented in details: one for a typical Saharan dust aerosol intrusion, 10 June 2012 and one for 12 July 2012 when a lofted layer consisting of biomass burning smoke extended from 3 to 4.5 km height. Optical Properties of Aerosols and Clouds software package (OPAC) classification and conversion factors were used to calculate mass concentrations. We found that calibrated depolarization measurements are critical to distinguish between smoke-reach aerosol during the winter and dust-reach aerosol during the summer, as well as between elevated aerosol layers having different origins. Good agreement was found between lidar retrievals and DREAM- Dust REgional Atmospheric Model forecasts in cases of Saharan dust. Our method was also compared against LIRIC (The Lidar/Radiometer Inversion Code) and very small differences were observed.

Saturation of subjective reward magnitude as a function of current and pulse frequency.

PubMed

Simmons, J M; Gallistel, C R

1994-02-01

In rats with electrodes in the medial forebrain bundle, the upper portion of the function relating the experienced magnitude of the reward to pulse frequency was determined at currents ranging from 100 to 1,000 microA. The pulse frequency required to produce an asymptotic level of reward was inversely proportional to current except at the lowest currents and highest pulse frequencies. At a given current, the subjective reward magnitude functions decelerated to an asymptote over an interval in which the pulse frequency doubled or tripled. The asymptotic level of reward was approximately constant for currents between 200 and 1,000 microA but declined substantially at currents at or below 100 microA and pulse frequencies at or above 250 to 400 pulses per second. The results are consistent with the hypothesis that the magnitude of the experienced reward depends only on the number of action potentials generated by the train of pulses in the bundle of reward-relevant axons.

A bursting potassium channel in isolated cholinergic synaptosomes of Torpedo electric organ.

PubMed Central

Edry-Schiller, J; Ginsburg, S; Rahamimoff, R

1991-01-01

1. Pinched-off cholinergic nerve terminals (synaptosomes) prepared from the electric organ of Torpedo ocelata were fused into large structures (greater than 20 microns) using dimethyl sulphoxide and polyethylene glycol 1500, as previously described for synaptic vesicles from the same organ. 2. The giant fused synaptosomes were easily amenable to the patch clamp technique and 293 seals with a resistance greater than 4 G omega were obtained in the 'cell-attached' configuration. In a large fraction of the experiments, an 'inside-out' patch configuration was achieved. 3. Several types of unitary ionic currents were observed. This study describes the most frequently observed single-channel activity which was found in 247 out of the 293 membrane patches (84.3%). 4. The single-channel current-voltage relation was linear between -60 and 20 mV and showed a slope conductance of 23.8 +/- 1.3 pS when the pipette contained 350-390 mM-Na+ and the bath facing the inside of the synaptosomal membrane contained 390 mM-K+. 5. From extrapolated reversal potential measurements, it was concluded that this channel has a large selectivity for K+ over Na+ (70.4 +/- 11.5, mean +/- S.E.M.). Chloride ions are not transported significantly through this potassium channel. 6. This potassium channel has a low probability of opening. The probability of being in the open state increases upon depolarization and reaches about 1% when the inside of the patch is 20 mV positive compared to the pipette side. 7. The mean channel open time increases with depolarization; thus the product current x time (= charge) also increases upon depolarization, showing properties of an outward rectifier. 8. The potassium channel in the giant synaptosome membrane has a bursting behaviour. Open-time distribution, closed-time distribution and a Poisson analysis indicate that the minimal kinetic scheme requires one open state and three closed states. PMID:1654418

Comparison between Trichel pulse in negative corona and self-pulsing in other configurations

NASA Astrophysics Data System (ADS)

Xia, Qing; Zhang, Yu; He, Feng; Qin, Yu; Jiang, Zhaorui; Ouyang, Jiting

2018-02-01

We present here a comparison study on self-pulsing phenomena in negative corona, hollow cathode discharges (HCD) and parallel-plate discharge in air. The voltage-current (V-I) curve, the waveforms of self-pulsed currents, and the time-resolved images of the pulsed discharge are measured under various operating conditions. It is experimentally evidenced that the Trichel pulse in a negative corona and the self-pulsing in HCD and/or parallel-plate discharge have similar features as well as spatial-temporal developing process. It is suggested that they should have a similar mechanism that the pulsing reflects the mode transition of discharge between the low-current Townsend and the high-current normal glow. The pulse rising corresponds to the breakdown and formation of temporal glow discharge in a background of low-current Townsend discharge, while the decay edge relates to the transition back to Townsend discharge. The pulse interval is the re-building process of the space charge layer of high density to ensure the glow breakdown.

Computational modeling of epidural cortical stimulation

NASA Astrophysics Data System (ADS)

Wongsarnpigoon, Amorn; Grill, Warren M.

2008-12-01

Epidural cortical stimulation (ECS) is a developing therapy to treat neurological disorders. However, it is not clear how the cortical anatomy or the polarity and position of the electrode affects current flow and neural activation in the cortex. We developed a 3D computational model simulating ECS over the precentral gyrus. With the electrode placed directly above the gyrus, about half of the stimulus current flowed through the crown of the gyrus while current density was low along the banks deep in the sulci. Beneath the electrode, neurons oriented perpendicular to the cortical surface were depolarized by anodic stimulation, and neurons oriented parallel to the boundary were depolarized by cathodic stimulation. Activation was localized to the crown of the gyrus, and neurons on the banks deep in the sulci were not polarized. During regulated voltage stimulation, the magnitude of the activating function was inversely proportional to the thickness of the CSF and dura. During regulated current stimulation, the activating function was not sensitive to the thickness of the dura but was slightly more sensitive than during regulated voltage stimulation to the thickness of the CSF. Varying the width of the gyrus and the position of the electrode altered the distribution of the activating function due to changes in the orientation of the neurons beneath the electrode. Bipolar stimulation, although often used in clinical practice, reduced spatial selectivity as well as selectivity for neuron orientation.

Pacemaker rate and depolarization block in nigral dopamine neurons: a somatic sodium channel balancing act

PubMed Central

Tucker, Kristal R.; Huertas, Marco A.; Horn, John P.; Canavier, Carmen C.; Levitan, Edwin S.

2012-01-01

Midbrain dopamine (DA) neurons are slow intrinsic pacemakers that undergo depolarization (DP) block upon moderate stimulation. Understanding DP block is important because it has been correlated with the clinical efficacy of chronic antipsychotic drug treatment. Here we describe how voltage-gated sodium (NaV) channels regulate DP block and pacemaker activity in DA neurons of the substantia nigra using rat brain slices. The distribution, density and gating of NaV currents were manipulated by blocking native channels with tetrodotoxin and by creating virtual channels and anti-channels with dynamic clamp. Although action potentials initiate in the axon initial segment (AIS) and NaV channels are distributed in multiple dendrites, selective reduction of NaV channel activity in the soma was sufficient to decrease pacemaker frequency and increase susceptibility to DP block. Conversely, increasing somatic NaV current density raised pacemaker frequency and lowered susceptibility to DP block. Finally, when NaV currents were restricted to the soma, pacemaker activity occurred at abnormally high rates due to excessive local subthreshold NaV current. Together with computational simulations, these data show that both the slow pacemaker rate and the sensitivity to DP block that characterizes DA neurons result from the low density of somatic NaV channels. More generally, we conclude that the somatodendritic distribution of NaV channels is a major determinant of repetitive spiking frequency. PMID:23077037

Rivastigmine blocks voltage-activated K+ currents in dissociated rat hippocampal neurons

PubMed Central

Pan, Yaping; Xu, Xianghua; Wang, Xiaoliang

2003-01-01

Rivastigmine is an acetylcholinesterase inhibitor used in Alzheimer's disease therapy. In the present study, we investigated the effects of rivastigmine on the transient outward K+ current (IK(A)) and the delayed rectifier K+ current (IK(DR)) in acutely dissociated rat hippocampal pyramidal neurons using the whole-cell patch-clamp technique. Rivastigmine inhibited the amplitudes of IK(A) and IK(DR) in a reversible and concentration-dependent manner. At a concentration of 100 μM, rivastigmine inhibited IK(A) and IK(DR), recorded when the cells were depolarized from −50 to +40 mV, by 65.9 (P<0.01) and 67.3% (P<0.01), respectively. The IC50 values for IK(A) and IK(DR) were 3.8 and 1.7 μM, respectively. The decay time constant of IK(A), recorded following a test pulse to +40 mV, was prolonged reversibly by rivastigmine at concentrations of 10 and 100 μM (both P<0.05). Rivastigmine affected the voltage dependence of IK(A) and IK(DR). At a concentration of 10 μM, it shifted the steady-state inactivation curve of IK(A) towards more negative potentials by −11 mV (P<0.05), but had no effect on the steady-state activation curve or the recovery from inactivation. Regarding the kinetic properties of IK(DR), 10 μM rivastigmine shifted the steady-state activation and inactivation curves towards more negative potentials by −10 (P<0.05) and −27 mV (P<0.01), respectively. Our findings that rivastigmine inhibits IK(A) and IK(DR) in rat hippocampal pyramidal neurons suggest that this agent has other pharmacological actions besides its antiacetylcholinesterase activity. PMID:14504131

Electrophysiological effects of tachykinins and capsaicin on guinea-pig bronchial parasympathetic ganglion neurones.

PubMed Central

Myers, A C; Undem, B J

1993-01-01

1. We evaluated the effects of neurokinins, tachykinin analogues, or capsaicin on passive membrane properties of guinea-pig bronchial parasympathetic neurones using intracellular recording techniques. 2. Substance P (SP) and the tachykinin analogue, acetyl-[Arg6,Sar9,Met(O2)11]-SP(6-11) (ASMSP), at concentrations selective for the neurokinin (NK)-1 receptor subtype, depolarized the resting potential (3 and 5 mV, respectively) with no change in input resistance. Neurokinin A and beta Ala8NKA(4-10), at concentrations selective for the NK-2 receptor subtype (0.1 microM), were without effect. 3. Neurokinin B (NKB) and [Asp5,6,methyl-Phe8]SP(5-11) (senktide analogue), at concentrations selective for NK-3 receptor subtype, elicited maximum depolarizations of 16 +/- 2 mV for both agonists. The peak of the depolarization was associated with an decrease in membrane resistance (35 +/- 4 and 50 +/- 7%, respectively). 4. Capsaicin (1 microM) elicited a 3-24 mV depolarization of the resting potential of thirteen of eighteen bronchial ganglion neurones and decreased the input resistance of seven of thirteen of these neurones. The effects of capsaicin were reduced by desensitization with senktide analogue at a concentration selective for the NK-3 receptor subtype, whereas a non-peptide NK-1 receptor antagonist had no effect. 5. Using voltage clamp analysis, capsaicin and senktide analogue evoked an inward current and an increase in membrane conductance at the resting membrane potential. The reversal potential for senktide analogue was estimated to be + 4 mV. 6. These data support the hypothesis that neurokinin-containing nerve terminals are localized within guinea-pig bronchial parasympathetic ganglia and, when released, the predominant effect of the neurokinins is by activation of NK-3 receptors. PMID:7508508

Distribution of Electromechanical Delay in the Heart: Insights from a Three-Dimensional Electromechanical Model

PubMed Central

Gurev, V.; Constantino, J.; Rice, J.J.; Trayanova, N.A.

2010-01-01

In the intact heart, the distribution of electromechanical delay (EMD), the time interval between local depolarization and myocyte shortening onset, depends on the loading conditions. The distribution of EMD throughout the heart remains, however, unknown because current experimental techniques are unable to evaluate three-dimensional cardiac electromechanical behavior. The goal of this study was to determine the three-dimensional EMD distributions in the intact ventricles for sinus rhythm (SR) and epicardial pacing (EP) by using a new, to our knowledge, electromechanical model of the rabbit ventricles that incorporates a biophysical representation of myofilament dynamics. Furthermore, we aimed to ascertain the mechanisms that underlie the specific three-dimensional EMD distributions. The results revealed that under both conditions, the three-dimensional EMD distribution is nonuniform. During SR, EMD is longer at the epicardium than at the endocardium, and is greater near the base than at the apex. After EP, the three-dimensional EMD distribution is markedly different; it also changes with the pacing rate. For both SR and EP, late-depolarized regions were characterized with significant myofiber prestretch caused by the contraction of the early-depolarized regions. This prestretch delays myofiber-shortening onset, and results in a longer EMD, giving rise to heterogeneous three-dimensional EMD distributions. PMID:20682251

Triple-wavelength lidar observations of the linear depolarization ratio of dried marine particles

NASA Astrophysics Data System (ADS)

Haarig, Moritz; Ansmann, Albert; Baars, Holger; Engelmann, Ronny; Althausen, Dietrich; Bohlmann, Stephanie; Gasteiger, Josef; Farrell, David

2018-04-01

For aerosol typing with lidar, sea salt particles are usually assumed to be spherical with a consequently low depolarization ratio. Evidence of dried marine particles at the top of the humid marine aerosol layer with a depolarization ratio up to 0.1 has been found at predominately maritime locations on Barbados and in the Southern Atlantic. The depolarization ratio for these probably cubic sea salt particles has been measured at three wavelengths (355, 532 and 1064 nm) simultaneously for the first time and compared to model simulations.

Longitudinal polarization periodicity of unpolarized light passing through a double wedge depolarizer.

PubMed

de Sande, Juan Carlos G; Santarsiero, Massimo; Piquero, Gemma; Gori, Franco

2012-12-03

The polarization characteristics of unpolarized light passing through a double wedge depolarizer are studied. It is found that the degree of polarization of the radiation propagating after the depolarizer is uniform across transverse planes after the depolarizer, but it changes from one plane to another in a periodic way giving, at different distances, unpolarized, partially polarized, or even perfectly polarized light. An experiment is performed to confirm this result. Measured values of the Stokes parameters and of the degree of polarization are in complete agreement with the theoretical predictions.

The comprehensive electrophysiological study of curcuminoids on delayed-rectifier K+ currents in insulin-secreting cells.

PubMed

Kuo, Ping-Chung; Yang, Chia-Jung; Lee, Yu-Chi; Chen, Pei-Chun; Liu, Yen-Chin; Wu, Sheng-Nan

2018-01-15

Curcumin (CUR) has been demonstrated to induce insulin release from pancreatic β-cells; however, how curcuminoids (including demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC)) exert any possible effects on membrane ion currents inherently in insulin-secreting cells remains largely unclear. The effects of CUR and other structurally similar curcuminoids on ion currents in rat insulin-secreting (INS-1) insulinoma cells were therefore investigated in this study. The effects of these compounds on ionic currents and membrane potential were studied by patch-clamp technique. CUR suppressed the amplitude of delayed-rectifier K + current (I K(DR) ) in a time-, state- and concentration-dependent manner in these cells and the inhibition was not reversed by diazoxide, nicorandil or chlorotoxin. The value of dissociation constant for CUR-induced suppression of I K(DR) in INS-1 cells was 1.26μM. Despite the inability of CUR to alter the activation rate of I K(DR) , it accelerated current inactivation elicited by membrane depolarization. Increasing CUR concentrations shifted the inactivation curve of I K(DR) to hyperpolarized potential and slowed the recovery of I K(DR) inactivation. CUR, DMC, and BDMC all exerted depressant actions on I K(DR) amplitude to a similar magnitude, although DMC and BDMC did not increase current inactivation clearly. CUR slightly suppressed the peak amplitude of voltage-gated Na + current. CUR, DMC and BDMC depolarized the resting potential and increased firing frequency of action potentials. The CUR-mediated decrease of I K(DR) and the increase of current inactivation also occurred in βTC-6 INS-1 cells. Taken these results together, these effects may be one of the possible mechanisms contributing their insulin-releasing effect. Copyright © 2017 Elsevier B.V. All rights reserved.

Chlorovirus-mediated membrane depolarization of Chlorella alters secondary active transport of solutes.

PubMed

Agarkova, Irina; Dunigan, David; Gurnon, James; Greiner, Timo; Barres, Julia; Thiel, Gerhard; Van Etten, James L

2008-12-01

Paramecium bursaria chlorella virus 1 (PBCV-1) is the prototype of a family of large, double-stranded DNA, plaque-forming viruses that infect certain eukaryotic chlorella-like green algae from the genus Chlorovirus. PBCV-1 infection results in rapid host membrane depolarization and potassium ion release. One interesting feature of certain chloroviruses is that they code for functional potassium ion-selective channel proteins (Kcv) that are considered responsible for the host membrane depolarization and, as a consequence, the efflux of potassium ions. This report examines the relationship between cellular depolarization and solute uptake. Annotation of the virus host Chlorella strain NC64A genome revealed 482 putative transporter-encoding genes; 224 are secondary active transporters. Solute uptake experiments using seven radioactive compounds revealed that virus infection alters the transport of all the solutes. However, the degree of inhibition varied depending on the solute. Experiments with nystatin, a drug known to depolarize cell membranes, produced changes in solute uptake that are similar but not identical to those that occurred during virus infection. Therefore, these studies indicate that chlorovirus infection causes a rapid and sustained depolarization of the host plasma membrane and that this depolarization leads to the inhibition of secondary active transporters that changes solute uptake.

Chlorovirus-Mediated Membrane Depolarization of Chlorella Alters Secondary Active Transport of Solutes▿

PubMed Central

Agarkova, Irina; Dunigan, David; Gurnon, James; Greiner, Timo; Barres, Julia; Thiel, Gerhard; Van Etten, James L.

2008-01-01

Paramecium bursaria chlorella virus 1 (PBCV-1) is the prototype of a family of large, double-stranded DNA, plaque-forming viruses that infect certain eukaryotic chlorella-like green algae from the genus Chlorovirus. PBCV-1 infection results in rapid host membrane depolarization and potassium ion release. One interesting feature of certain chloroviruses is that they code for functional potassium ion-selective channel proteins (Kcv) that are considered responsible for the host membrane depolarization and, as a consequence, the efflux of potassium ions. This report examines the relationship between cellular depolarization and solute uptake. Annotation of the virus host Chlorella strain NC64A genome revealed 482 putative transporter-encoding genes; 224 are secondary active transporters. Solute uptake experiments using seven radioactive compounds revealed that virus infection alters the transport of all the solutes. However, the degree of inhibition varied depending on the solute. Experiments with nystatin, a drug known to depolarize cell membranes, produced changes in solute uptake that are similar but not identical to those that occurred during virus infection. Therefore, these studies indicate that chlorovirus infection causes a rapid and sustained depolarization of the host plasma membrane and that this depolarization leads to the inhibition of secondary active transporters that changes solute uptake. PMID:18842725

miR-1 is increased in pulmonary hypertension and downregulates Kv1.5 channels in rat pulmonary arteries.

PubMed

Mondejar-Parreño, Gema; Callejo, María; Barreira, Bianca; Morales-Cano, Daniel; Esquivel-Ruiz, Sergio; Moreno, Laura; Cogolludo, Angel; Perez-Vizcaino, Francisco

2018-05-02

■The expression of miR-1 is increased in lungs from the Hyp/Su5416 PAH rat model. ■PASMC from this animal model are more depolarised and show decreased expression and activity of Kv1.5. ■miR-1 directly targets Kv1.5 channels, reduces Kv1.5 activity and induces membrane depolarization. ■Antagomir-1 prevents Kv1.5 channel downregulation and the depolarization induced by hypoxia/Su5416 exposition. Impairment of voltage-dependent potassium channel (Kv) plays a central role in the development of cardiovascular diseases, including pulmonary arterial hypertension (PAH). MicroRNAs (miRNAs) are non-coding RNAs that regulate gene expression by binding to the 3'-UTR region of specific mRNAs. The aim of this study was to analyze the effects of miR-1 on Kv channel function in pulmonary arteries (PA). Kv channel activity was studied in PA from healthy animals transfected with miR-1 or scrambled-miR. Kv currents were studied using the whole-cell configuration of patch-clamp technique. The characterization of the Kv1.5 currents was performed with the selective inhibitor DPO-1. miR-1 expression was increased and Kv1.5 channels were decreased in lungs from a rat model of PAH induced by hypoxia and Su5416. miR-1 transfection increased cell capacitance, reduced Kv1.5 currents and induced membrane depolarization in isolated pulmonary artery smooth muscle cells (PASMCs). Luciferase reporter assay indicated that KCNA5, which encodes Kv1.5 channels, is a direct target gene of miR-1. Incubation of PA with Su5416 and hypoxia (3% O 2 ) increased miR-1 and induced a decline in Kv1.5 currents, which was prevented by antagomiR-1. In conclusion, these data indicate that miR-1 induces PASMC hypertrophy and reduces the activity and expression of Kv channels, suggesting a pathophysiological role in PAH. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

NaV1.4 mutations cause hypokalaemic periodic paralysis by disrupting IIIS4 movement during recovery

PubMed Central

Lehmann-Horn, Frank; Fan, Chunxiang; Wolf, Markus; Winston, Vern; Merlini, Luciano

2014-01-01

Hypokalaemic periodic paralysis is typically associated with mutations of voltage sensor residues in calcium or sodium channels of skeletal muscle. To date, causative sodium channel mutations have been studied only for the two outermost arginine residues in S4 voltage sensor segments of domains I to III. These mutations produce depolarization of skeletal muscle fibres in response to reduced extracellular potassium, owing to an inward cation-selective gating pore current activated by hyperpolarization. Here, we describe mutations of the third arginine, R3, in the domain III voltage sensor i.e. an R1135H mutation which was found in two patients in separate families and a novel R1135C mutation identified in a third patient in another family. Muscle fibres from a patient harbouring the R1135H mutation showed increased depolarization tendency at normal and reduced extracellular potassium compatible with the diagnosis. Additionally, amplitude and rise time of action potentials were reduced compared with controls, even for holding potentials at which all NaV1.4 are fully recovered from inactivation. These findings may be because of an outward omega current activated at positive potentials. Expression of R1135H/C in mammalian cells indicates further gating defects that include significantly enhanced entry into inactivation and prolonged recovery that may additionally contribute to action potential inhibition at the physiological resting potential. After S4 immobilization in the outward position, mutant channels produce an inward omega current that most likely depolarizes the resting potential and produces the hypokalaemia-induced weakness. Gating current recordings reveal that mutations at R3 inhibit S4 deactivation before recovery, and molecular dynamics simulations suggest that this defect is caused by disrupted interactions of domain III S2 countercharges with S4 arginines R2 to R4 during repolarization of the membrane. This work reveals a novel mechanism of disrupted S4 translocation for hypokalaemic periodic paralysis mutations at arginine residues located below the gating pore constriction of the voltage sensor module. PMID:24549961

Ionic currents in the guinea-pig taenia coli.

PubMed Central

Inomata, H; Kao, C Y

1976-01-01

Short segments of portions of taenia coli of the guinea-pig averaging 54 mum X 219 mum X ca. 200 mum have been studied by a double sucrose-gap voltage-clamp technique. 2. The average total capacitance was 0-4 muF, corresponding to approximately 10(4) cells, if a specific membrane capacitance of 3 muF/cm2 were assumed. 3. A significant resistance, averaging 11-4omega, was in series with the membrane, and seriously limited the accuracy of the voltage control possible. 4. On depolarization, an early transient inward current was followed by a late maintained outwary current. 5. The late current was carried mainly by K+, because its direction could be reversed if the preparation were first depolarized in isotonic K2SO4 and held back to the original resting potential. 6. After appropriate corrections for residual capacitative and leakage currents, a reversal potential for the late current (Eb) was determined to be 15-20 mV more negative than the natural resting potential. It was not affected by the amplitude or the duration of the activating voltage step, but could be changed by prolonged applications of holding current. 7. At rest, the ratio of PNa:PK was 0-16:1; for Eb it was 0-05:1. 8. The reversal potential for the transient early inward current (Ea) averaged 22 mV in Krebs-bicarbonate solution, but was shifted to about 35 mV when the late current was first suppressed with tetraethylammonium ion. The shift suggested that there was some overlap of the early and late currents. 9. Reduction of [Na+]o to 50% of normal, or replacement of all Na+ with dimethyldiethanol ammonium ion and choline ion, failed to cause any significant shifts in the reversal potential of the early current or reduce the magnitude of the early current. 10. Reduction of [Ca2+]o to 0-25 or 0-1 of the normal caused shifts of the Ea toward the negative and reductions in the early current. These changes can occur without changes in the maximum chord conductance of the early current, such as might happen in ordinary Krebs-bicarbonate solution, or in preparations which had been depolarized by prior treatment with isotonic K2SO4 and then held back to the original membrane voltage. 11. Increase of [Ca2+]o to 5 times normal increased the early inward current, and the maximum chord conductances of the early and late currents, but did not shift the Ea. 12. In preparations pretreated with TEA, increasing [Ca2+]o to 5 times normal shifted Ea toward 45 mV. 13. The various observations are interpreted to mean that the early current in the taenia coli is carried principally by influx of Ca2+, and not by Na+. PMID:1255524

Biophysically based mathematical modeling of interstitial cells of Cajal slow wave activity generated from a discrete unitary potential basis.

PubMed

Faville, R A; Pullan, A J; Sanders, K M; Koh, S D; Lloyd, C M; Smith, N P

2009-06-17

Spontaneously rhythmic pacemaker activity produced by interstitial cells of Cajal (ICC) is the result of the entrainment of unitary potential depolarizations generated at intracellular sites termed pacemaker units. In this study, we present a mathematical modeling framework that quantitatively represents the transmembrane ion flows and intracellular Ca2+ dynamics from a single ICC operating over the physiological membrane potential range. The mathematical model presented here extends our recently developed biophysically based pacemaker unit modeling framework by including mechanisms necessary for coordinating unitary potential events, such as a T-Type Ca2+ current, Vm-dependent K+ currents, and global Ca2+ diffusion. Model simulations produce spontaneously rhythmic slow wave depolarizations with an amplitude of 65 mV at a frequency of 17.4 cpm. Our model predicts that activity at the spatial scale of the pacemaker unit is fundamental for ICC slow wave generation, and Ca2+ influx from activation of the T-Type Ca2+ current is required for unitary potential entrainment. These results suggest that intracellular Ca2+ levels, particularly in the region local to the mitochondria and endoplasmic reticulum, significantly influence pacing frequency and synchronization of pacemaker unit discharge. Moreover, numerical investigations show that our ICC model is capable of qualitatively replicating a wide range of experimental observations.

The Electrophysiology of Electric Organs of Marine Electric Fishes

PubMed Central

Bennett, M. V. L.; Wurzel, M.; Grundfest, H.

1961-01-01

Single electroplaques of Torpedo nobiliana have been studied with microelectrode recording. Direct evidence is presented that the only electrogenically reactive membrane of the cells is on the innervated surface and that this membrane is electrically inexcitable. Responses are not evoked by depolarizing currents applied to this membrane, but only by stimulating the innervating nerve fibers. The responses arise after a latency of 1 to 3 msec. This latency is not affected by large depolarizing or hyperpolarizing changes in membrane potential. Various properties that have been theoretically associated with electrically inexcitable responses have been also demonstrated to occur in the electroplaques. The neurally evoked response is not propagated actively in the membrane and may have different amplitudes and forms in closely adjacent regions. The maximal responses frequently are slightly larger than the recorded resting potential but the apparent small overshoot may be due to difficulty in recording the full resting potential. The responses are subject to electrochemical gradation and appear inverted in sign on applying strong outward currents across the innervated membrane. This membrane is cholinoceptive and shows marked desensitization. The membrane of the uninnervated surface has a very low resistance, a factor that aids maximum output of current during the discharge of the electric organ. PMID:19873534

Mechanism of H2 histamine receptor dependent modulation of body temperature and neuronal activity in the medial preoptic nucleus

PubMed Central

Tabarean, Iustin V.; Sanchez-Alavez, Manuel; Sethi, Jasmine

2012-01-01

Histamine is involved in the central control of arousal, circadian rhythms and metabolism. The preoptic area, a region that contains thermoregulatory neurons is the main locus of histamine modulation of body temperature. Here we report that in mice histamine activates H2 subtype receptors in the medial preoptic nucleus (MPON) and induces hyperthermia. We also found that a population of glutamatergic MPON neurons express H2 receptors and are excited by histamine or H2 specific agonists. The agonists decreased the input resistance of the neuron and increased the depolarizing “sag” observed during hyperpolarizing current injections. Furthermore, at −60 mV holding potential activation of H2 receptors induced an inward current that was blocked by ZD7288, a specific blocker of the hyperpolarization activated cationic current (Ih). Indeed, activation of H2 receptors resulted in increased Ih amplitude in response to hyperpolarizing voltage steps and a depolarizing shift in its voltage-dependent activation. The neurons excited by H2 specific agonism expressed the HCN1 and HCN2 channel subunits. Our data indicate that at the level of the MPON histamine influences thermoregulation by increasing the firing rate of glutamatergic neurons that express H2 receptors. PMID:22366077

Mechanism of H₂ histamine receptor dependent modulation of body temperature and neuronal activity in the medial preoptic nucleus.

PubMed

Tabarean, Iustin V; Sanchez-Alavez, Manuel; Sethi, Jasmine

2012-08-01

Histamine is involved in the central control of arousal, circadian rhythms and metabolism. The preoptic area, a region that contains thermoregulatory neurons is the main locus of histamine modulation of body temperature. Here we report that in mice, histamine activates H(2) subtype receptors in the medial preoptic nucleus (MPON) and induces hyperthermia. We also found that a population of glutamatergic MPON neurons express H(2) receptors and are excited by histamine or H(2) specific agonists. The agonists decreased the input resistance of the neuron and increased the depolarizing "sag" observed during hyperpolarizing current injections. Furthermore, at -60 mV holding potential, activation of H(2) receptors induced an inward current that was blocked by ZD7288, a specific blocker of the hyperpolarization activated cationic current (I(h)). Indeed, activation of H(2) receptors resulted in increased I(h) amplitude in response to hyperpolarizing voltage steps and a depolarizing shift in its voltage-dependent activation. The neurons excited by H(2) specific agonism expressed the HCN1 and HCN2 channel subunits. Our data indicate that at the level of the MPON histamine influences thermoregulation by increasing the firing rate of glutamatergic neurons that express H(2) receptors. Copyright © 2012 Elsevier Ltd. All rights reserved.

The voltage dependence of NADPH oxidase reveals why phagocytes need proton channels

NASA Astrophysics Data System (ADS)

DeCoursey, Thomas E.; Morgan, Deri; Cherny, Vladimir V.

2003-04-01

The enzyme NADPH oxidase in phagocytes is important in the body's defence against microbes: it produces superoxide anions (O2-, precursors to bactericidal reactive oxygen species). Electrons move from intracellular NADPH, across a chain comprising FAD (flavin adenine dinucleotide) and two haems, to reduce extracellular O2 to O2-. NADPH oxidase is electrogenic, generating electron current (Ie) that is measurable under voltage-clamp conditions. Here we report the complete current-voltage relationship of NADPH oxidase, the first such measurement of a plasma membrane electron transporter. We find that Ie is voltage-independent from -100mV to >0mV, but is steeply inhibited by further depolarization, and is abolished at about +190mV. It was proposed that H+ efflux mediated by voltage-gated proton channels compensates Ie, because Zn2+ and Cd2+ inhibit both H+ currents and O2- production. Here we show that COS-7 cells transfected with four NADPH oxidase components, but lacking H+ channels, produce O2- in the presence of Zn2+ concentrations that inhibit O2- production in neutrophils and eosinophils. Zn2+ does not inhibit NADPH oxidase directly, but through effects on H+ channels. H+ channels optimize NADPH oxidase function by preventing membrane depolarization to inhibitory voltages.

Role of an inward rectifier K+ current and of hyperpolarization in human myoblast fusion

PubMed Central

Liu, J-H; Bijlenga, P; Fischer-Lougheed, J; Occhiodoro, T; Kaelin, A; Bader, C R; Bernheim, L

1998-01-01

The role of K+ channels and membrane potential in myoblast fusion was evaluated by examining resting membrane potential and timing of expression of K+ currents at three stages of differentiation of human myogenic cells: undifferentiated myoblasts, fusion-competent myoblasts (FCMBs), and freshly formed myotubes. Two K+ currents contribute to a hyperpolarization of myoblasts prior to fusion: IK(NI), a non-inactivating delayed rectifier, and IK(IR), an inward rectifier. IK(NI) density is low in undifferentiated myoblasts, increases in FCMBs and declines in myotubes. On the other hand, IK(IR) is expressed in 28 % of the FCMBs and in all myotubes. IK(IR) is reversibly blocked by Ba2+ or Cs+. Cells expressing IK(IR) have resting membrane potentials of −65 mV. A block by Ba2+ or Cs+ induces a depolarization to a voltage determined by IK(NI) (−32 mV). Cs+ and Ba2+ ions reduce myoblast fusion. It is hypothesized that the IK(IR)-mediated hyperpolarization allows FCMBs to recruit Na+, K+ and T-type Ca2+ channels which are present in these cells and would otherwise be inactivated. FCMBs, rendered thereby capable of firing action potentials, could amplify depolarizing signals and may accelerate fusion. PMID:9705997

Neutron depolarization effects in a high-Tc superconductor (abstract)

NASA Astrophysics Data System (ADS)

Nunes, A. C.; Pickart, S. J.; Crow, L.; Goyette, R.; McGuire, T. R.; Shinde, S.; Shaw, T. M.

1988-11-01

Using the polarized beam small-angle neutron scattering spectrometer at the Rhode Island Nuclear Science Center Reactor, we have observed significant depolarization of a neutron beam by passage through polycrystalline high-Tc superconductors, specifically 123 Y-Ba-Cu-O prepared and characterized at the IBM Watson Research Center. We believe that this technique will prove useful in studying aspects of these materials, such as the penetration depth of shielding currents, the presence and structure of trapped flux vortices, and grain size effects on the supercurrent distribution in polycrystalline samples. The two samples showed sharp transitions at 87 and 89 K, and have been studied at temperatures of 77 K; the second sample has also been studied at 4 K. The transition to the superconducting state was monitored by the shift in resonant frequency of a coil surrounding the sample. No measurable depolarization was observed in either sample at 77 K in both the field-cooled and zero-field-cooled states, using applied fields of 0 (nominal), 54, and 1400 Oe. This negative result may be connected with the fact that the material is still in the reversible region as indicated by susceptibility measurements, but it allows an estimate of the upper bound of possible inhomogeneous internal fields, assuming a distance scale for the superconducting regions. For the 10-μm grain size suggested by photomicrographs, this upper bound for the field turns out to be 1.2 kOe, which seems reasonable. At 4 K a significant depolarization was observed when the sample was cooled in low fields and a field of 1400 Oe was subsequently applied. This result suggests that flux lines are penetrating the sample. Further investigations are being carried out to determine the field and temperature dependence of the depolarization, and attempts will be made to model it quantitatively in terms of possible internal field distributions. We are also searching for possible diffraction effects from ordered vortex arrays and plan to extend the measurements to Bi and Tl compositions. These results will be reported in detail elsewhere.

Calcium permeable AMPA receptors and autoreceptors in external tufted cells of rat olfactory bulb

PubMed Central

Ma, Jie; Lowe, Graeme

2007-01-01

Glomeruli are functional units of the olfactory bulb responsible for early processing of odor information encoded by single olfactory receptor genes. Glomerular neural circuitry includes numerous external tufted (ET) cells whose rhythmic burst firing may mediate synchronization of bulbar activity with the inhalation cycle. Bursting is entrained by glutamatergic input from olfactory nerve terminals, so specific properties of ionotropic glutamate receptors on ET cells are likely to be important determinants of olfactory processing. Particularly intriguing is recent evidence that α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors of juxta-glomerular neurons may permeate calcium. This could provide a novel pathway for regulating ET cell signaling. We tested the hypothesis that ET cells express functional calcium-permeable AMPA receptors. In rat olfactory bulb slices, excitatory postsynaptic currents (EPSCs) in ET cells were evoked by olfactory nerve shock, and by uncaging glutamate. We found attenuation of AMPA/kainate EPSCs by 1-naphthyl acetyl-spermine (NAS), an open-channel blocker specific for calcium permeable AMPA receptors. Cyclothiazide strongly potentiated EPSCs, indicating a major contribution from AMPA receptors. The current-voltage (I-V) relation of uncaging EPSCs showed weak inward rectification which was lost after > ~ 10 min of whole-cell dialysis, and was absent in NAS. In kainate-stimulated slices, Co2+ ions permeated cells of the glomerular layer. Large AMPA EPSCs were accompanied by fluorescence signals in fluo-4 loaded cells, suggesting calcium permeation. Depolarizing pulses evoked slow tail currents with pharmacology consistent with involvement of calcium permeable AMPA autoreceptors. Tail currents were abolished by Cd2+ and NBQX, and were sensitive to NAS block. Glutamate autoreceptors were confirmed by uncaging intracellular calcium to evoke a large inward current. Our results provide evidence that calcium permeable AMPA receptors reside on ET cells, and are divided into at least two functionally distinct pools – postsynaptic receptors at olfactory nerve synaptic terminals, and autoreceptors sensitive to glutamate released from dendrodendritic synapses. PMID:17156930

Sequential pictorial presentation of neural interaction in the retina. 2. The depolarizing and hyperpolarizing bipolar cells at rod terminals.

PubMed

Sjöstrand, F S

2002-01-01

Each rod is connected to one depolarizing and one hyperpolarizing bipolar cell. The synaptic connections of cone processes to each bipolar cell and presynaptically to the two rod-bipolar cell synapses establishes conditions for lateral interaction at this level. Thus, the cones raise the threshold for bipolar cell depolarization which is the basis for spatial brightness contrast enhancement and consequently for high visual acuity (Sjöstrand, 2001a). The cones facilitate ganglion cell depolarization by the bipolar cells and cone input prevents horizontal cell blocking of depolarization of the depolarizing bipolar cell, extending rod vision to low illumination. The combination of reduced cone input and transient hyperpolarization of the hyperpolarizing bipolar cell at onset of a light stimulus facilitates ganglion cell depolarization extensively at onset of the stimulus while no corresponding enhancement applies to the ganglion cell response at cessation of the stimulus, possibly establishing conditions for discrimination between on- vs. off-signals in the visual centre. Reduced cone input and hyperpolarization of the hyperpolarizing bipolar cell at onset of a light stimulus accounts for Granit's (1941) 'preexcitatory inhibition'. Presynaptic inhibition maintains transmitter concentration low in the synaptic gap at rod-bipolar cell and bipolar cell-ganglion cell synapses, securing proportional and amplified postsynaptic responses at these synapses. Perfect timing of variations in facilitatory and inhibitory input to the ganglion cell confines the duration of ganglion cell depolarization at onset and at cessation of a light stimulus to that of a single synaptic transmission.

Oxytocin Depolarizes Fast-Spiking Hilar Interneurons and Induces GABA Release onto Mossy Cells of the Rat Dentate Gyrus

PubMed Central

Harden, Scott W.; Frazier, Charles J.

2016-01-01

Delivery of exogenous oxytocin (OXT) to central oxytocin receptors (OXT-Rs) is currently being investigated as a potential treatment for conditions such as post-traumatic stress disorder (PTSD), depression, social anxiety, and autism spectrum disorder (ASD). Despite significant research implicating central OXT signaling in modulation of mood, affect, social behavior, and stress response, relatively little is known about the cellular and synaptic mechanisms underlying these complex actions, particularly in brain regions which express the OXT-R but lie outside of the hypothalamus (where OXT-synthesizing neurons reside). We report that bath application of low concentrations of the selective OXT-R agonist Thr4,Gly7-OXT (TGOT) reliably and robustly drives GABA release in the dentate gyrus in an action potential dependent manner. Additional experiments led to identification of a small subset of small hilar interneurons that are directly depolarized by acute application of TGOT. From a physiological perspective, TGOT-responsive hilar interneurons have high input resistance, rapid repolarization velocity during an action potential, and a robust afterhyperpolarization. Further, they fire irregularly (or stutter) in response to moderate depolarization, and fire quickly with minimal spike frequency accommodation in response to large current injections. From an anatomical perspective, TGOT responsive hilar interneurons have dense axonal arborizations in the hilus that were found close proximity with mossy cell somata and/or proximal dendrites, and also invade the granule cell layer. Further, they have primary dendrites that always extend into the granule cell layer, and sometimes have clear arborizations in the molecular layer. Overall, these data reveal a novel site of action for OXT in an important limbic circuit, and represent a significant step towards better understanding how endogenous OXT may modulate flow of information in hippocampal networks. PMID:27068005

Native pyroglutamation of huwentoxin-IV: a post-translational modification that increases the trapping ability to the sodium channel.

PubMed

Rong, Mingqiang; Duan, Zhigui; Chen, Juliang; Li, Jianglin; Xiao, Yuchen; Liang, Songping

2013-01-01

Huwentoxin-IV (HWTX-IV), a tetrodotoxin-sensitive (TTX-s) sodium channel antagonist, is found in the venom of the Chinese spider Ornithoctonus huwena. A naturally modified HWTX-IV (mHWTX-IV), having a molecular mass 18 Da lower than HWTX-IV, has also been isolated from the venom of the same spider. By a combination of enzymatic fragmentation and MS/MS de novo sequencing, mHWTX-IV has been shown to have the same amino acid sequence as that of HWTX-IV, except that the N-terminal glutamic acid replaced by pyroglutamic acid. mHWTX-IV inhibited tetrodotoxin-sensitive voltage-gated sodium channels of dorsal root ganglion neurons with an IC50 nearly equal to native HWTX-IV. mHWTX-IV showed the same activation and inactivation kinetics seen for native HWTX-IV. In contrast with HWTX-IV, which dissociates at moderate voltage depolarization voltages (+50 mV, 180000 ms), mHWTX-IV inhibition of TTX-sensitive sodium channels is not reversed by strong depolarization voltages (+200 mV, 500 ms). Recovery of Nav1.7current was voltage-dependent and was induced by extreme depolarization in the presence of HWTX-IV, but no obvious current was elicited after application of mHWTX-IV. Our data indicate that the N-terminal modification of HWTX-IV gives the peptide toxin a greater ability to trap the voltage sensor in the sodium channel. Loss of a negative charge, caused by cyclization at the N-terminus, is a possible reason why the modified toxin binds much stronger. To our knowledge, this is the first report of a pyroglutamic acid residue in a spider toxin; this modification seems to increase the trapping ability of the voltage sensor in the sodium channel.

Mechanism-based facilitated maturation of human pluripotent stem cell-derived cardiomyocytes

PubMed Central

Lieu, Deborah K.; Fu, Ji-Dong; Chiamvimonvat, Nipavan; Chan Tung, Kelvin W.; McNerney, Gregory P.; Huser, Thomas; Keller, Gordon; Kong, Chi-Wing

2013-01-01

Background Human embryonic stem cells (hESCs) can be efficiently and reproducibly directed into cardiomyocytes (CMs) using stage-specific induction protocols. However, their functional properties and suitability for clinical and other applications have not been evaluated. Methods and Results Here we showed that CMs derived from multiple pluripotent human stem cell lines (hESC: H1, HES2) and types (induced pluripotent stem cell or iPSC) using different in vitro differentiation protocols (embryoid body formation, endodermal induction, directed differentiation) commonly displayed immature, pro-arrhythmic action potential (AP) properties such as high-degree of automaticity, depolarized resting membrane potential (RMP), Phase 4- depolarization and delayed after-depolarization (DAD). Among the panoply of sarcolemmal ionic currents investigated (INa+/ICaL2+/IKr+/INCX+/If+/Ito+/IK1-/IKs-), we pinpointed the lack of the Kir2.1-encoded inwardly rectifying K+ current (IK1) as the single mechanistic contributor to the observed immature electrophysiological properties in hESC-CMs. Forced expression of Kir2.1 in hESC-CMs led to robust expression of Ba2+-sensitive IK1 and more importantly, completely ablated all the pro-arrhythmic AP traits, rendering the electrophysiological phenotype indistinguishable from the adult counterparts. These results provided the first link of a complex developmentally arrested phenotype to a major effector gene, and importantly, further led us to develop a biomimetic culturing strategy for enhancing maturation. Conclusions By providing the environmental cues that are missing in conventional culturing method, this approach did not require any genetic or pharmacological interventions. Our findings can facilitate clinical applications, drug discovery and cardiotoxicity screening by improving the yield, safety and efficacy of derived CMs. PMID:23392582

The elementary events of Ca2+ release elicited by membrane depolarization in mammalian muscle.

PubMed

Csernoch, L; Zhou, J; Stern, M D; Brum, G; Ríos, E

2004-05-15

Cytosolic [Ca(2+)] transients elicited by voltage clamp depolarization were examined by confocal line scanning of rat skeletal muscle fibres. Ca(2+) sparks were observed in the fibres' membrane-permeabilized ends, but not in responses to voltage in the membrane-intact area. Elementary events of the depolarization-evoked response could be separated either at low voltages (near -50 mV) or at -20 mV in partially inactivated cells. These were of lower amplitude, narrower and of much longer duration than sparks, similar to 'lone embers' observed in the permeabilized segments. Their average amplitude was 0.19 and spatial half-width 1.3 microm. Other parameters depended on voltage. At -50 mV average duration was 111 ms and latency 185 ms. At -20 mV duration was 203 ms and latency 24 ms. Ca(2+) release current, calculated on an average of events, was nearly steady at 0.5-0.6 pA. Accordingly, simulations of the fluorescence event elicited by a subresolution source of 0.5 pA open for 100 ms had morphology similar to the experimental average. Because 0.5 pA is approximately the current measured for single RyR channels in physiological conditions, the elementary fluorescence events in rat muscle probably reflect opening of a single RyR channel. A reconstruction of cell-averaged release flux at -20 mV based on the observed distribution of latencies and calculated elementary release had qualitatively correct but slower kinetics than the release flux in prior whole-cell measurements. The qualitative agreement indicates that global Ca(2+) release flux results from summation of these discrete events. The quantitative discrepancies suggest that the partial inactivation strategy may lead to events of greater duration than those occurring physiologically in fully polarized cells.

Native Pyroglutamation of Huwentoxin-IV: A Post-Translational Modification that Increases the Trapping Ability to the Sodium Channel

PubMed Central

Rong, Mingqiang; Duan, Zhigui; Chen, Juliang; Li, Jianglin; Xiao, Yuchen; Liang, Songping

2013-01-01

Huwentoxin-IV (HWTX-IV), a tetrodotoxin-sensitive (TTX-s) sodium channel antagonist, is found in the venom of the Chinese spider Ornithoctonus huwena. A naturally modified HWTX-IV (mHWTX-IV), having a molecular mass 18 Da lower than HWTX-IV, has also been isolated from the venom of the same spider. By a combination of enzymatic fragmentation and MS/MS de novo sequencing, mHWTX-IV has been shown to have the same amino acid sequence as that of HWTX-IV, except that the N-terminal glutamic acid replaced by pyroglutamic acid. mHWTX-IV inhibited tetrodotoxin-sensitive voltage-gated sodium channels of dorsal root ganglion neurons with an IC50 nearly equal to native HWTX-IV. mHWTX-IV showed the same activation and inactivation kinetics seen for native HWTX-IV. In contrast with HWTX-IV, which dissociates at moderate voltage depolarization voltages (+50 mV, 180000 ms), mHWTX-IV inhibition of TTX-sensitive sodium channels is not reversed by strong depolarization voltages (+200 mV, 500 ms). Recovery of Nav1.7current was voltage-dependent and was induced by extreme depolarization in the presence of HWTX-IV, but no obvious current was elicited after application of mHWTX-IV. Our data indicate that the N-terminal modification of HWTX-IV gives the peptide toxin a greater ability to trap the voltage sensor in the sodium channel. Loss of a negative charge, caused by cyclization at the N-terminus, is a possible reason why the modified toxin binds much stronger. To our knowledge, this is the first report of a pyroglutamic acid residue in a spider toxin; this modification seems to increase the trapping ability of the voltage sensor in the sodium channel. PMID:23826086

Contribution for Iron Vapor and Radiation Distribution Affected by Current Frequency of Pulsed Arc

NASA Astrophysics Data System (ADS)

Shimokura, Takuya; Mori, Yusuke; Iwao, Toru; Yumoto, Motoshige

Pulsed GTA welding has been used for improvement of stability, weld speed, and heat input control. However, the temperature and radiation power of the pulsed arc have not been elucidated. Furthermore, arc contamination by metal vapor changes the arc characteristics, e.g. by increasing radiation power. In this case, the metal vapor in pulsed GTA welding changes the distribution of temperature and radiation power as a function of time. This paper presents the relation between metal vapor and radiation power at different pulse frequencies. We calculate the Fe vapor distribution of the pulsed current. Results show that the Fe vapor is transported at fast arc velocity during the peak current period. During the base current period, the Fe vapor concentration is low and distribution is diffuse. The transition of Fe vapor distribution does not follow the pulsed current; the radiation power density distribution differs for high frequencies and low frequencies. In addition, the Fe vapor and radiation distribution are affected by the pulsed arc current frequency.

Factors that reverse the persistent depolarization produced by deprivation of oxygen and glucose in rat hippocampal CA1 neurons in vitro.

PubMed

Yamamoto, S; Tanaka, E; Shoji, Y; Kudo, Y; Inokuchi, H; Higashi, H

1997-08-01

In CA1 pyramidal neurons in rat hippocampal tissue slices, superfusion with ischemia-simulating medium produced a rapid depolarization after 6 min of exposure. The membrane potential eventually reached 0 after 5 min (a persistent depolarization), even when oxygen and glucose were reintroduced. The role of various ions in the reversal of this persistent depolarization after reintroduction of oxygen and glucose was investigated. The peak of the persistent depolarization was decreased in solutions containing reduced Na+ or Ca2+ and in solutions containing Co2+ or Ni2+. In contrast, the depolarization was not affected by reduction of external K+ or Cl- or by addition of tetrodotoxin (TTX), flunarizine, or nifedipine. These results suggest that sustained Na+ and Ca2+ influxes produce the persistent depolarization. The membrane potential recovered after reintroduction of oxygen and glucose in low Ca2+, low Cl-, or K+-rich medium and in TTX- or tetraethylammonium-containing medium, but not in low Na+ or low K+ medium and in flunarizine- or nifedipine-containing medium. Either reduction in extracellular Ca2+ or addition of Co2+ was the most effective in promoting recovery from the persistent depolarization, suggesting that Ca2+ influx has a key role in causing the membrane dysfunction. The peak of the persistent depolarization was reduced by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), DL-2-amino-5-phosphonopentanoic acid (AP5), DL-amino-3-phosphonopropionic acid (AP3), or DL-amino-4-phosphonobutyric acid, suggesting that activation of non-N-methyl-D-aspartate (non-NMDA), NMDA, and metabotropic glutamate (Glu) receptors is involved in the generation and maintenance of the persistent depolarization. Among these Glu receptor antagonists, only CNQX or AP5 was able to reduce dose dependently the level of depolarization, suggesting that Ca2+ influx via both alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate type II receptors and NMDA receptors contributes to the membrane dysfunction. trans-1-aminocyclopentane-1,3-dicarboxylic acid (t-ACPD) did not affect the peak potential of the persistent depolarization, but it dose-dependently restored the membrane potential. AP3 antagonized the protective action of t-ACPD. The membrane potential also recovered after reintroduction when the slice was pretreated by 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetraacetoxymethyl ester, ryanodol 3-(1H-pyrrole-2-carboxylate), 8-(diethylamino)octyl-3,4,5-trimethoxybenzoate hydrochloride, and procaine, suggesting that raised [Ca2+]i from Ca2+-induced Ca2+ release pool contributes to the membrane dysfunction. It, therefore, is concluded that raised [Ca2+]i has a dominant role in causing irreversible changes. The increase in [Ca2+]i during the persistent depolarization may be the result of Ca2+ entry via both a leaky membrane and Glu-activated receptor channels as well as Ca2+ released from internal stores.

Microstructures of Ni-AlN composite coatings prepared by pulse electrodeposition technology

NASA Astrophysics Data System (ADS)

Xia, Fafeng; Xu, Huibin; Liu, Chao; Wang, Jinwu; Ding, Junjie; Ma, Chunhua

2013-04-01

Ni-AlN composite coating was fabricated onto the surface of steel substrates by using pulse electrodeposition (PED) technique in this work. The effect of pulse current on the nucleation and growth of grains was investigated using transmission electronic microscopy (TEM), X-ray diffraction (XRD), scanning electronic microscopy (SEM) and atomic force microscopy (AFM), respectively. The results show that the contents of AlN nanoparticles increase with density of pulse current and on-duty ratio of pulse current increasing. Whereas the size of nickel grains decreases with density of pulse current increasing and on-duty ratio of pulse current decreasing. Ni-AlN composite coating consists of crystalline nickel (˜68 nm) and AlN particles (˜38 nm). SEM and AFM observations show that the composite coatings obtained by PED showed more compact surfaces and less grain sizes, whereas those obtained by direct current electrodepositing have rougher surfaces and bigger grain sizes.

Antagonism of Lidocaine Inhibition by Open-Channel Blockers That Generate Resurgent Na Current

PubMed Central

Bant, Jason S.; Aman, Teresa K.; Raman, Indira M.

2013-01-01

Na channels that generate resurgent current express an intracellular endogenous open-channel blocking protein, whose rapid binding upon depolarization and unbinding upon repolarization minimizes fast and slow inactivation. Na channels also bind exogenous compounds, such as lidocaine, which functionally stabilize inactivation. Like the endogenous blocking protein, these use-dependent inhibitors bind most effectively at depolarized potentials, raising the question of how lidocaine-like compounds affect neurons with resurgent Na current. We therefore recorded lidocaine inhibition of voltage-clamped, tetrodotoxin-sensitive Na currents in mouse Purkinje neurons, which express a native blocking protein, and in mouse hippocampal CA3 pyramidal neurons with and without a peptide from the cytoplasmic tail of NaVβ4 (the β4 peptide), which mimics endogenous open-channel block. To control channel states during drug exposure, lidocaine was applied with rapid-solution exchange techniques during steps to specific voltages. Inhibition of Na currents by lidocaine was diminished by either the β4 peptide or the native blocking protein. In peptide-free CA3 cells, prolonging channel opening with a site-3 toxin, anemone toxin II, reduced lidocaine inhibition; this effect was largely occluded by open-channel blockers, suggesting that lidocaine binding is favored by inactivation but prevented by open-channel block. In constant 100 μM lidocaine, current-clamped Purkinje cells continued to fire spontaneously. Similarly, the β4 peptide reduced lidocaine-dependent suppression of spiking in CA3 neurons in slices. Thus, the open-channel blocking protein responsible for resurgent current acts as a natural antagonist of lidocaine. Neurons with resurgent current may therefore be less susceptible to use-dependent Na channel inhibitors used as local anesthetic, antiarrhythmic, and anticonvulsant drugs. PMID:23486968

PKC-dependent regulation of Kv7.5 channels by the bronchoconstrictor histamine in human airway smooth muscle cells.

PubMed

Haick, Jennifer M; Brueggemann, Lioubov I; Cribbs, Leanne L; Denning, Mitchell F; Schwartz, Jeffrey; Byron, Kenneth L

2017-06-01

Kv7 potassium channels have recently been found to be expressed and functionally important for relaxation of airway smooth muscle. Previous research suggests that native Kv7 currents are inhibited following treatment of freshly isolated airway smooth muscle cells with bronchoconstrictor agonists, and in intact airways inhibition of Kv7 channels is sufficient to induce bronchiolar constriction. However, the mechanism by which Kv7 currents are inhibited by bronchoconstrictor agonists has yet to be elucidated. In the present study, native Kv7 currents in cultured human trachealis smooth muscle cells (HTSMCs) were observed to be inhibited upon treatment with histamine; inhibition of Kv7 currents was associated with membrane depolarization and an increase in cytosolic Ca 2+ ([Ca 2+ ] cyt ). The latter response was inhibited by verapamil, a blocker of L-type voltage-sensitive Ca 2+ channels (VSCCs). Protein kinase C (PKC) has been implicated as a mediator of bronchoconstrictor actions, although the targets of PKC are not clearly established. We found that histamine treatment significantly and dose-dependently suppressed currents through overexpressed wild-type human Kv7.5 (hKv7.5) channels in cultured HTSMCs, and this effect was inhibited by the PKC inhibitor Ro-31-8220 (3 µM). The PKC-dependent suppression of hKv7.5 currents corresponded with a PKC-dependent increase in hKv7.5 channel phosphorylation. Knocking down or inhibiting PKCα, or mutating hKv7.5 serine 441 to alanine, abolished the inhibitory effects of histamine on hKv7.5 currents. These findings provide the first evidence linking PKC activation to suppression of Kv7 currents, membrane depolarization, and Ca 2+ influx via L-type VSCCs as a mechanism for histamine-induced bronchoconstriction. Copyright © 2017 the American Physiological Society.

[Decreased A-type potassium current mediates the hyperexcitability of nociceptive neurons in the chronically compressed dorsal root ganglia].

PubMed

Yan, Ni; Li, Xiao-Han; Cheng, Qi; Yan, Jin; Ni, Xin; Sun, Ji-Hu

2007-04-25

The excitability of nociceptive neurons increases in the intact dorsal root ganglion (DRG) after a chronic compression, but the underlying mechanisms are still unclear. The aim of this study was to investigate the ionic mechanisms underlying the hyperexcitability of nociceptive neurons in the compressed ganglion. Chronic compression of DRG (CCD) was produced in adult rats by inserting two rods through the intervertebral foramina to compress the L4 DRG and the ipsilateral L5 DRG. After 5-7 d, DRG somata were dissociated and placed in culture for 12-18 h. In sharp electrode recording model, the lower current threshold and the depolarized membrane potential in the acutely dissociated CCD neurons were detected, indicating that hyperexcitability is intrinsic to the soma. Since voltage-gated K(+) (Kv) channels in the primary sensory neurons are important for the regulation of excitability, we hypothesized that CCD would alter K(+) current properties in the primary sensory neurons. We examined the effects of 4-aminopyridine (4-AP), a specific antagonist of A-type potassium channel, on the excitability of the control DRG neurons. With 4-AP in the external solution, the control DRG neurons depolarized (with discharges in some cells) and their current threshold decreased as the CCD neurons demonstrated, indicating the involvement of decreased A-type potassium current in the hyperexcitability of the injured neurons. Furthermore, the alteration of A-type potassium current in nociceptive neurons in the compressed ganglion was investigated with the whole-cell patch-clamp recording model. CCD significantly decreased A-type potassium current density in nociceptive DRG neurons. These data suggest that a reduction in A-type potassium current contributes, at least in part, to the increase in neuron excitability that may lead to the development of pain and hyperalgesia associated with CCD.

Tachykininergic slow depolarization of motoneurones evoked by descending fibres in the neonatal rat spinal cord.

PubMed Central

Kurihara, T; Yoshioka, K; Otsuka, M

1995-01-01

1. In the isolated spinal cord of the neonatal rat, repetitive electrical stimulation of the upper cervical region elicited a prolonged depolarization of lumbar motoneurones (L3-5) lasting 1-2 min, which was recorded extracellularly from ventral roots, or intracellularly. 2. This depolarizing response was markedly depressed by the excitatory amino acid receptor antagonists D-(-)-2-amino-5-phosphonovaleric acid (D-APV, 30 microM) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM). The remaining response was further depressed by a 5-hydroxytryptamine (5-HT) receptor antagonist, ketanserin (3 microM). 3. In the presence of these antagonists, a small part of the depolarizing response of slow time course remained, and this response was partially blocked by the tachykinin NK1 receptor antagonists GR71251 (0.3-5 microM) and RP67580 (0.3-1 microM). In contrast, RP68651 (0.3-1 microM), the inactive enantiomer of RP67580, had no effect on the depolarizing response. 4. The slow depolarizing response in the presence of D-APV, CNQX and ketanserin was markedly potentiated by a peptidase inhibitor, thiorphan (1 microM). 5. This descending fibre-evoked slow depolarization became smaller after prolonged treatment (5-7 h) with 5,7-dihydroxytryptamine (10 microM), a neurotoxin for 5-HT neurones. Under such conditions, the effects of thiorphan and GR71251 on the slow depolarization were virtually absent. 6. Under the action of D-APV, CNQX and ketanserin, applications of tachykinins, substance P and neurokinin A produced depolarizing responses of lumbar motoneurones, and the responses were depressed by GR71251 and potentiated by thiorphan. 7. These results suggest that tachykinins contained in serotonergic fibres serve as neurotransmitters mediating the descending fibre-evoked slow excitatory postsynaptic potentials in motoneurones. PMID:7562617

Activation of K+ channels by lanthanum contributes to the block of transmitter release in chick and rat sympathetic neurons.

PubMed

Przywara, D A; Bhave, S V; Bhave, A; Chowdhury, P S; Wakade, T D; Wakade, A R

1992-01-01

We studied the effects of lanthanum (La3+) on the release of 3H-norepinephrine (3H-NE), intracellular Ca2+ concentration, and voltage clamped Ca2+ and K+ currents in cultured sympathetic neurons. La3+ (0.1 to 10 microM) produced concentration-dependent inhibition of depolarization induced Ca2+ influx and 3H-NE release. La3+ was more potent and more efficacious in blocking 3H-NE release than the Ca(2+)-channel blockers cadmium and verapamil, which never blocked more than 70% of the release. At 3 microM, La3+ produced a complete block of the electrically stimulated rise in intracellular free Ca2+ ([Ca2+]i) in the cell body and the growth cone. The stimulation-evoked release of 3H-NE was also completely blocked by 3 microM La3+. However, 3 microM La3+ produced only a partial block of voltage clamped Ca2+ current (ICa). Following La3+ (10 microM) treatment 3H-NE release could be evoked by high K+ stimulation of neurons which were refractory to electrical stimulation. La3+ (1 microM) increased the hyperpolarization activated, 4-aminopyridine (4-AP) sensitive, transient K+ current (IA) with little effect on the late outward current elicited from depolarized holding potentials. We conclude that the effective block of electrically stimulated 3H-NE release is a result of the unique ability of La3+ to activate a stabilizing, outward K+ current at the same concentration that it blocks inward Ca2+ current.

High speed, high current pulsed driver circuit

DOEpatents

Carlen, Christopher R.

2017-03-21

Various technologies presented herein relate to driving a LED such that the LED emits short duration pulses of light. This is accomplished by driving the LED with short duration, high amplitude current pulses. When the LED is driven by short duration, high amplitude current pulses, the LED emits light at a greater amplitude compared to when the LED is driven by continuous wave current.

Selective depolarization of the muscle membrane in frog nerve-muscle preparations by a chromatographically purified extract of the dinoflagellate Ostreopsis lenticularis

PubMed Central

Meunier, Frédéric A; Mercado, José A; Molgó, Jordi; Tosteson, Thomas R; Escalona de Motta, Gladys

1997-01-01

The actions of a chromatographically identified extract of the marine dinoflagellate Ostreopsis lenticularis, named ostreotoxin-3 (OTX-3), were studied on frog isolated neuromuscular preparations. OTX-3 (1–10 μg ml−1) applied to cutaneous pectoris nerve-muscle preparations depolarized skeletal muscle fibres and caused spontaneous contractions. The depolarization was neither reversed by prolonged washing nor by (+)-tubocurarine. OTX-3 decreased the amplitude of miniature end plate potentials (m.e.p.ps) but did not affect their frequency. Extracellular recording of compound action potentials revealed that OTX-3 affected neither excitability nor conduction along intramuscular nerve branches. End-plate potentials (e.p.ps) elicited by nerve stimulation were reduced in amplitude by OTX-3 and even showed reversed polarity in junctions deeply depolarized by the toxin. Membrane depolarization induced by OTX-3 was decreased about 70% in muscles pretreated for 30 min with 10 μM tetrodotoxin. In contrast, muscles pretreated with 5 μM μ-conotoxin GIIIA were completely insensitive to OTX-3-induced depolarization. OTX-3 did not affect e.p.p. amplitude and the quantal content of e.p.ps in junctions in which muscle depolarization was abolished by μ-conotoxin GIIIA. OTX-3 is a novel type of sodium-channel activating toxin that discriminates between nerve and skeletal muscle membranes. PMID:9249261

Process for applying control variables having fractal structures

DOEpatents

Bullock, IV, Jonathan S.; Lawson, Roger L.

1996-01-01

A process and apparatus for the application of a control variable having a fractal structure to a body or process. The process of the present invention comprises the steps of generating a control variable having a fractal structure and applying the control variable to a body or process reacting in accordance with the control variable. The process is applicable to electroforming where first, second and successive pulsed-currents are applied to cause the deposition of material onto a substrate, such that the first pulsed-current, the second pulsed-current, and successive pulsed currents form a fractal pulsed-current waveform.

Process for applying control variables having fractal structures

DOEpatents

Bullock, J.S. IV; Lawson, R.L.

1996-01-23

A process and apparatus are disclosed for the application of a control variable having a fractal structure to a body or process. The process of the present invention comprises the steps of generating a control variable having a fractal structure and applying the control variable to a body or process reacting in accordance with the control variable. The process is applicable to electroforming where first, second and successive pulsed-currents are applied to cause the deposition of material onto a substrate, such that the first pulsed-current, the second pulsed-current, and successive pulsed currents form a fractal pulsed-current waveform. 3 figs.

Featuring of transient tunneling current by voltage pulse and application to an electrochemical biosensor

NASA Astrophysics Data System (ADS)

Yun, Jun Yeon; Lee, Won Cheol; Choi, Seong Wook; Park, Young June

2018-03-01

We suggest a voltage pulse method for detecting the transient tunneling current component (faradaic current component) in a metal/redox-active monolayer/electrolyte system. After applying the pulse to the metal electrode, the capacitive current prevails; therefore, it is difficult to extract the tunneling current, which carries information on the biochemical reactions occurring between the biomarkers in the electrolyte and the self-assembled monolayer (SAM) as the probe peptide system. Instead of waiting until the capacitive current diminishes, and thereby, the tunneling current also decreases, we try to extract the tunneling current in an early stage of the pulse. The method is based on the observation that the capacitive current becomes symmetrized in the positive and negative pulses after introducing the SAM on the metal electrode. When the energy level of the redox molecule is higher than the Fermi level of the metal under zero-bias condition, the tunneling current in the negative pulse can be extracted by subtracting the capacitive current obtained from the positive pulse, where the tunneling current is neglected. The experiment conducted for detecting trypsin as a biomarker shows that the method enhances the sensitivity and the specific-to-nonspecific ratio of the sensor device in the case of the nonspecific protein-abundant electrolyte solution, as evinced by cyclic voltammetry measurements in comparison.

Light-controlled inhibition of malignant glioma by opsin gene transfer

PubMed Central

Yang, F; Tu, J; Pan, J-Q; Luo, H-L; Liu, Y-H; Wan, J; Zhang, J; Wei, P-F; Jiang, T; Chen, Y-H; Wang, L-P

2013-01-01

Glioblastomas are aggressive cancers with low survival rates and poor prognosis because of their highly proliferative and invasive capacity. In the current study, we describe a new optogenetic strategy that selectively inhibits glioma cells through light-controlled membrane depolarization and cell death. Transfer of the engineered opsin ChETA (engineered Channelrhodopsin-2 variant) gene into primary human glioma cells or cell lines, but not normal astrocytes, unexpectedly decreased cell proliferation and increased mitochondria-dependent apoptosis, upon light stimulation. These optogenetic effects were mediated by membrane depolarization-induced reductions in cyclin expression and mitochondrial transmembrane potential. Importantly, the ChETA gene transfer and light illumination in mice significantly inhibited subcutaneous and intracranial glioma growth and increased the survival of the animals bearing the glioma. These results uncover an unexpected effect of opsin ion channels on glioma cells and offer the opportunity for the first time to treat glioma using a light-controllable optogenetic approach. PMID:24176851

Light-controlled inhibition of malignant glioma by opsin gene transfer.

PubMed

Yang, F; Tu, J; Pan, J-Q; Luo, H-L; Liu, Y-H; Wan, J; Zhang, J; Wei, P-F; Jiang, T; Chen, Y-H; Wang, L-P

2013-10-31

Glioblastomas are aggressive cancers with low survival rates and poor prognosis because of their highly proliferative and invasive capacity. In the current study, we describe a new optogenetic strategy that selectively inhibits glioma cells through light-controlled membrane depolarization and cell death. Transfer of the engineered opsin ChETA (engineered Channelrhodopsin-2 variant) gene into primary human glioma cells or cell lines, but not normal astrocytes, unexpectedly decreased cell proliferation and increased mitochondria-dependent apoptosis, upon light stimulation. These optogenetic effects were mediated by membrane depolarization-induced reductions in cyclin expression and mitochondrial transmembrane potential. Importantly, the ChETA gene transfer and light illumination in mice significantly inhibited subcutaneous and intracranial glioma growth and increased the survival of the animals bearing the glioma. These results uncover an unexpected effect of opsin ion channels on glioma cells and offer the opportunity for the first time to treat glioma using a light-controllable optogenetic approach.

MULTIPLY: Development of a European HSRL Airborne Facility

NASA Astrophysics Data System (ADS)

Binietoglou, Ioannis; Serikov, Ilya; Nicolae, Doina; Amiridis, Vassillis; Belegante, Livio; Boscornea, Andrea; Brugmann, Bjorn; Costa Suros, Montserrat; Hellmann, David; Kokkalis, Panagiotis; Linne, Holger; Stachlewska, Iwona; Vajaiac, Sorin-Nicolae

2016-08-01

MULTIPLY is a novel airborne high spectral resolution lidar (HSRL) currently under development by a consortium of European institutions from Romania, Germany, Greece, and Poland. Its aim is to contribute to calibration and validations activities of the upcoming ESA aerosol sensing missions like ADM-Aeolus, EarthCARE and the Sentinel-3/-4/-5/-5p which include products related to atmospheric aerosols. The effectiveness of these missions depends on independent airborne measurements to develop and test the retrieval methods, and validate mission products following launch. The aim of ESA's MULTIPLY project is to design, develop, and test a multi-wavelength depolarization HSRL for airborne applications. The MULTIPLY lidar will deliver the aerosol extinction and backscatter coefficient profiles at three wavelengths (355nm, 532nm, 1064nm), as well as profiles of aerosol intensive parameters (Ångström exponents, extinction- to-backscatter ratios, and linear particle depolarization ratios).

Current density imaging sequence for monitoring current distribution during delivery of electric pulses in irreversible electroporation.

PubMed

Serša, Igor; Kranjc, Matej; Miklavčič, Damijan

2015-01-01

Electroporation is gaining its importance in everyday clinical practice of cancer treatment. For its success it is extremely important that coverage of the target tissue, i.e. treated tumor, with electric field is within the specified range. Therefore, an efficient tool for the electric field monitoring in the tumor during delivery of electroporation pulses is needed. The electric field can be reconstructed by the magnetic resonance electric impedance tomography method from current density distribution data. In this study, the use of current density imaging with MRI for monitoring current density distribution during delivery of irreversible electroporation pulses was demonstrated. Using a modified single-shot RARE sequence, where four 3000 V and 100 μs long pulses were included at the start, current distribution between a pair of electrodes inserted in a liver tissue sample was imaged. Two repetitions of the sequence with phases of refocusing radiofrequency pulses 90° apart were needed to acquire one current density image. For each sample in total 45 current density images were acquired to follow a standard protocol for irreversible electroporation where 90 electric pulses are delivered at 1 Hz. Acquired current density images showed that the current density in the middle of the sample increased from first to last electric pulses by 60%, i.e. from 8 kA/m2 to 13 kA/m2 and that direction of the current path did not change with repeated electric pulses significantly. The presented single-shot RARE-based current density imaging sequence was used successfully to image current distribution during delivery of short high-voltage electric pulses. The method has a potential to enable monitoring of tumor coverage by electric field during irreversible electroporation tissue ablation.

Micro-pulse polarization lidar at 1.5  μm using a single superconducting nanowire single-photon detector.

PubMed

Qiu, Jiawei; Xia, Haiyun; Shangguan, Mingjia; Dou, Xiankang; Li, Manyi; Wang, Chong; Shang, Xiang; Lin, Shengfu; Liu, Jianjiang

2017-11-01

An all-fiber, eye-safe and micro-pulse polarization lidar is demonstrated with a polarization-maintaining structure, incorporating a single superconducting nanowire single-photon detector (SNSPD) at 1.5 μm. The time-division multiplexing technique is used to achieve a calibration-free optical layout. A single piece of detector is used to detect the backscatter signals at two orthogonal states in an alternative sequence. Thus, regular calibration of the two detectors in traditional polarization lidars is avoided. The signal-to-noise ratio of the lidar is guaranteed by using an SNSPD, providing high detection efficiency and low dark count noise. The linear depolarization ratio (LDR) of the urban aerosol is observed horizontally over 48 h in Hefei [N31°50'37'', E117°15'54''], when a heavy air pollution is spreading from the north to the central east of China. Phenomena of LDR bursts are detected at a location where a building is under construction. The lidar results show good agreement with the data detected from a sun photometer, a 532 nm visibility lidar, and the weather forecast information.

Short- and long-term functional plasticity of white matter induced by oligodendrocyte depolarization in the hippocampus.

PubMed

Yamazaki, Yoshihiko; Fujiwara, Hiroki; Kaneko, Kenya; Hozumi, Yasukazu; Xu, Ming; Ikenaka, Kazuhiro; Fujii, Satoshi; Tanaka, Kenji F

2014-08-01

Plastic changes in white matter have received considerable attention in relation to normal cognitive function and learning. Oligodendrocytes and myelin, which constitute the white matter in the central nervous system, can respond to neuronal activity with prolonged depolarization of membrane potential and/or an increase in the intracellular Ca(2+) concentration. Depolarization of oligodendrocytes increases the conduction velocity of an action potential along axons myelinated by the depolarized oligodendrocytes, indicating that white matter shows functional plasticity, as well as structural plasticity. However, the properties and mechanism of oligodendrocyte depolarization-induced functional plastic changes in white matter are largely unknown. Here, we investigated the functional plasticity of white matter in the hippocampus using mice with oligodendrocytes expressing channelrhodopsin-2. Using extracellular recordings of compound action potentials at the alveus of the hippocampus, we demonstrated that light-evoked depolarization of oligodendrocytes induced early- and late-onset facilitation of axonal conduction that was dependent on the magnitude of oligodendrocyte depolarization; the former lasted for approximately 10 min, whereas the latter continued for up to 3 h. Using whole-cell recordings from CA1 pyramidal cells and recordings of antidromic action potentials, we found that the early-onset short-lasting component included the synchronization of action potentials. Moreover, pharmacological analysis demonstrated that the activation of Ba(2+) -sensitive K(+) channels was involved in early- and late-onset facilitation, whereas 4-aminopyridine-sensitive K(+) channels were only involved in the early-onset component. These results demonstrate that oligodendrocyte depolarization induces short- and long-term functional plastic changes in the white matter of the hippocampus and plays active roles in brain functions. © 2014 Wiley Periodicals, Inc.

Self-pulsing in a low-current hollow cathode discharge: From Townsend to glow discharge

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qin, Yu; School of Aerospace Engineering, Beijing Institute of Technology, Beijing 100081; Xie, Kan, E-mail: xiekan@bit.edu.cn

We investigate the self-pulsing phenomenon of a low current cavity discharge in a cylindrical hollow cathode in pure argon. The waveforms of pulsed current and voltage are measured, and the time-averaged and time-resolved images of hollow cathode discharge are recorded by using high-speed intensified charge coupled device camera. The results show that the self-pulsing is a mode transition between low-current stage of Townsend discharge and high-current stage of glow discharge. During the self-pulsing, the current rising time relates to the dissipation of space charges, and the decay time relates to the reconstruction of the virtual anode by the accumulation ofmore » positive ions. Whether or not space charges can form and keep the virtual anode is responsible for the discharge mode and hence plays an important role in the self-pulsing phenomenon in low current hollow cathode discharge.« less

Neuronal Depolarization Drives Increased Dopamine Synaptic Vesicle Loading via VGLUT.

PubMed

Aguilar, Jenny I; Dunn, Matthew; Mingote, Susana; Karam, Caline S; Farino, Zachary J; Sonders, Mark S; Choi, Se Joon; Grygoruk, Anna; Zhang, Yuchao; Cela, Carolina; Choi, Ben Jiwon; Flores, Jorge; Freyberg, Robin J; McCabe, Brian D; Mosharov, Eugene V; Krantz, David E; Javitch, Jonathan A; Sulzer, David; Sames, Dalibor; Rayport, Stephen; Freyberg, Zachary

2017-08-30

The ability of presynaptic dopamine terminals to tune neurotransmitter release to meet the demands of neuronal activity is critical to neurotransmission. Although vesicle content has been assumed to be static, in vitro data increasingly suggest that cell activity modulates vesicle content. Here, we use a coordinated genetic, pharmacological, and imaging approach in Drosophila to study the presynaptic machinery responsible for these vesicular processes in vivo. We show that cell depolarization increases synaptic vesicle dopamine content prior to release via vesicular hyperacidification. This depolarization-induced hyperacidification is mediated by the vesicular glutamate transporter (VGLUT). Remarkably, both depolarization-induced dopamine vesicle hyperacidification and its dependence on VGLUT2 are seen in ventral midbrain dopamine neurons in the mouse. Together, these data suggest that in response to depolarization, dopamine vesicles utilize a cascade of vesicular transporters to dynamically increase the vesicular pH gradient, thereby increasing dopamine vesicle content. Copyright © 2017 Elsevier Inc. All rights reserved.

Neuronal Depolarization Drives Increased Dopamine Synaptic Vesicle Loading via VGLUT

PubMed Central

Aguilar, Jenny I.; Dunn, Matthew; Mingote, Susana; Karam, Caline S.; Farino, Zachary J.; Sonders, Mark S.; Choi, Se Joon; Grygoruk, Anna; Zhang, Yuchao; Cela, Carolina; Choi, Ben Jiwon; Flores, Jorge; Freyberg, Robin J.; McCabe, Brian D.; Mosharov, Eugene V.; Krantz, David E.; Javitch, Jonathan A.; Sulzer, David; Sames, Dalibor; Rayport, Stephen; Freyberg, Zachary

2017-01-01

SUMMARY The ability of presynaptic dopamine terminals to tune neurotransmitter release to meet the demands of neuronal activity is critical to neurotransmission. Although vesicle content has been assumed to be static, in vitro data increasingly suggest that cell activity modulates vesicle content. Here, we use a coordinated genetic, pharmacological, and imaging approach in Drosophila to study the presynaptic machinery responsible for these vesicular processes in vivo. We show that cell depolarization increases synaptic vesicle dopamine content prior to release via vesicular hyperacidification. This depolarization-induced hyperacidification is mediated by the vesicular glutamate transporter (VGLUT). Remarkably, both depolarization-induced dopamine vesicle hyperacidification and its dependence on VGLUT2 are seen in ventral midbrain dopamine neurons in the mouse. Together, these data suggest that in response to depolarization, dopamine vesicles utilize a cascade of vesicular transporters to dynamically increase the vesicular pH gradient, thereby increasing dopamine vesicle content. PMID:28823729

Transient outwardly rectifying A currents are involved in the firing rate response to altered CO2 in chemosensitive locus coeruleus neurons from neonatal rats

PubMed Central

Li, Ke-Yong

2013-01-01

The effect of hypercapnia on outwardly rectifying currents was examined in locus coeruleus (LC) neurons in slices from neonatal rats [postnatal day 3 (P3)–P15]. Two outwardly rectifying currents [4-aminopyridine (4-AP)-sensitive transient current and tetraethyl ammonium (TEA)-sensitive sustained current] were found in LC neurons. 4-AP induced a membrane depolarization of 3.6 ± 0.6 mV (n = 4), while TEA induced a smaller membrane depolarization of 1.2 ± 0.3 mV (n = 4). Hypercapnic acidosis (HA) inhibited both currents. The maximal amplitude of the TEA-sensitive current was reduced by 52.1 ± 4.5% (n = 5) in 15% CO2 [extracellular pH (pHo) 7.00, intracellular pH (pHi) 6.96]. The maximal amplitude of the 4-AP-sensitive current was reduced by 34.5 ± 3.0% (n = 6) in 15% CO2 (pHo 7.00, pHi 6.96), by 29.4 ± 6.8% (n = 6) in 10% CO2 (pHo 7.15, pHi 7.14), and increased by 29.0 ± 6.4% (n = 6) in 2.5% CO2 (pHo 7.75, pHi 7.35). 4-AP completely blocked hypercapnia-induced increased firing rate, but TEA did not affect it. When LC neurons were exposed to HA with either pHo or pHi constant, the 4-AP-sensitive current was inhibited. The data show that the 4-AP-sensitive current (likely an A current) is inhibited by decreases in either pHo or pHi. The change of the A current by various levels of CO2 is correlated with the change in firing rate induced by CO2, implicating the 4-AP-sensitive current in chemosensitive signaling in LC neurons. PMID:23948777

Use-dependent activation of neuronal Kv1.2 channel complexes.

PubMed

Baronas, Victoria A; McGuinness, Brandon R; Brigidi, G Stefano; Gomm Kolisko, Rachel N; Vilin, Yury Y; Kim, Robin Y; Lynn, Francis C; Bamji, Shernaz X; Yang, Runying; Kurata, Harley T

2015-02-25

In excitable cells, ion channels are frequently challenged by repetitive stimuli, and their responses shape cellular behavior by regulating the duration and termination of bursts of action potentials. We have investigated the behavior of Shaker family voltage-gated potassium (Kv) channels subjected to repetitive stimuli, with a particular focus on Kv1.2. Genetic deletion of this subunit results in complete mortality within 2 weeks of birth in mice, highlighting a critical physiological role for Kv1.2. Kv1.2 channels exhibit a unique property described previously as "prepulse potentiation," in which activation by a depolarizing step facilitates activation in a subsequent pulse. In this study, we demonstrate that this property enables Kv1.2 channels to exhibit use-dependent activation during trains of very brief depolarizations. Also, Kv subunits usually assemble into heteromeric channels in the central nervous system, generating diversity of function and sensitivity to signaling mechanisms. We demonstrate that other Kv1 channel types do not exhibit use-dependent activation, but this property is conferred in heteromeric channel complexes containing even a single Kv1.2 subunit. This regulatory mechanism is observed in mammalian cell lines as well as primary cultures of hippocampal neurons. Our findings illustrate that use-dependent activation is a unique property of Kv1.2 that persists in heteromeric channel complexes and may influence function of hippocampal neurons. Copyright © 2015 the authors 0270-6474/15/353515-10$15.00/0.

Ground-based lidar measurements from Ny-Ålesund during ASTAR 2007: a statistical overview

NASA Astrophysics Data System (ADS)

Hoffmann, A.; Ritter, C.; Stock, M.; Shiobara, M.; Lampert, A.; Maturilli, M.; Orgis, T.; Neuber, R.; Herber, A.

2009-07-01

During the Arctic Study of Tropospheric Aerosol, Clouds and Radiation (ASTAR) in March and April 2007, measurements obtained at the AWIPEV Research station in Ny-Ålesund, Spitsbergen (operated by the Alfred-Wegener-Institute for Polar and Marine Research and the Institut polaire français Paul-Emile Victor), supported the airborne campaign. This included Lidar data from the Koldewey Aerosol Raman Lidar (KARL) and the Micro Pulse Lidar (MPL), located in the atmospheric observatory as well as photometer data and the daily launched radiosonde. The MPL features nearly continuous measurements; the KARL was switched on whenever weather conditions allowed observations (145 h in 61 days). From 1 March to 30 April, 71 meteorological balloon soundings were performed and compared with the corresponding MPL measurements; photometer measurements are available from 18 March. For the KARL data, a statistical overview based on the optical properties backscatter ratio and volume depolarization can be given. The altitudes of the occurrence of the named features (subvisible and visible ice and water as well as mixed-phase clouds, aerosol layers) as well as their dependence on different air mass origins are analyzed. Although the spring 2007 was characterized by rather clean conditions, diverse case studies of cloud and aerosol occurrence during March and April 2007 are presented in more detail, including temporal development and main optical properties as backscatter, depolarization and extinction coefficients. Links between air mass origins and optical properties can be presumed but need further evidence.

Multiple scattering effects on the Linear Depolarization Ratio (LDR) measured during CaPE by a Ka-band air-borne radar

NASA Technical Reports Server (NTRS)

Iguchi, Toshio; Meneghini, Robert

1993-01-01

Air-borne radar measurements of thunderstorms were made as part of the CaPE (Convection and Precipitation/Electrification) experiment in Florida in July 1991. The radar has two channels, X-band (10 GHz) and Ka-band (34.5 GHz), and is capable of measuring cross-polarized returns as well as co-polarized returns. In stratiform rain, the cross-polarized components can be observed only at the bright band region and from the surface reflection. The linear depolarization ratios (LDR's) measured at X-band and Ka-band at the bright band are nearly equal. In convective rain, however, the LDR in Ka-band often exceeds the X-band LDR by several dB, and sometimes by more than 10 dB, reaching LDR values of up to -5 dB over heavy convective rain. For randomly oriented hydrometeors, such high LDR values cannot be explained by single scattering from non-spherical scattering particles alone. Because the LDR by single backscatter depends weakly on the wavelength, the difference between the Ka-band and X-band LDR's suggests that multiple scattering effects prevail in the Ka-band LDR. In order to test this inference, the magnitude of the cross-polarized component created by double scattering was calculated using the parameters of the airborne radar, which for both frequencies has beamwidths of 5.1 degrees and pulse widths of 0.5 microsecond. Uniform rain beyond the range of 3 km is assumed.

Multiple current peaks in room-temperature atmospheric pressure homogenous dielectric barrier discharge plasma excited by high-voltage tunable nanosecond pulse in air

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, De-Zheng; Wang, Wen-Chun; Zhang, Shuai

2013-05-13

Room temperature homogenous dielectric barrier discharge plasma with high instantaneous energy efficiency is acquired by using nanosecond pulse voltage with 20-200 ns tunable pulse width. Increasing the voltage pulse width can lead to the generation of regular and stable multiple current peaks in each discharge sequence. When the voltage pulse width is 200 ns, more than 5 organized current peaks can be observed under 26 kV peak voltage. Investigation also shows that the organized multiple current peaks only appear in homogenous discharge mode. When the discharge is filament mode, organized multiple current peaks are replaced by chaotic filament current peaks.

Reduced motor neuron excitability is an important contributor to weakness in a rat model of sepsis.

PubMed

Nardelli, Paul; Vincent, Jacob A; Powers, Randall; Cope, Tim C; Rich, Mark M

2016-08-01

The mechanisms by which sepsis triggers intensive care unit acquired weakness (ICUAW) remain unclear. We previously identified difficulty with motor unit recruitment in patients as a novel contributor to ICUAW. To study the mechanism underlying poor recruitment of motor units we used the rat cecal ligation and puncture model of sepsis. We identified striking dysfunction of alpha motor neurons during repetitive firing. Firing was more erratic, and often intermittent. Our data raised the possibility that reduced excitability of motor neurons was a significant contributor to weakness induced by sepsis. In this study we quantified the contribution of reduced motor neuron excitability and compared its magnitude to the contributions of myopathy, neuropathy and failure of neuromuscular transmission. We injected constant depolarizing current pulses (5s) into the soma of alpha motor neurons in the lumbosacral spinal cord of anesthetized rats to trigger repetitive firing. In response to constant depolarization, motor neurons in untreated control rats fired at steady and continuous firing rates and generated smooth and sustained tetanic motor unit force as expected. In contrast, following induction of sepsis, motor neurons were often unable to sustain firing throughout the 5s current injection such that force production was reduced. Even when firing, motor neurons from septic rats fired erratically and discontinuously, leading to irregular production of motor unit force. Both fast and slow type motor neurons had similar disruption of excitability. We followed rats after recovery from sepsis to determine the time course of resolution of the defect in motor neuron excitability. By one week, rats appeared to have recovered from sepsis as they had no piloerection and appeared to be in no distress. The defects in motor neuron repetitive firing were still striking at 2weeks and, although improved, were present at one month. We infer that rats suffered from weakness due to reduced motor neuron excitability for weeks after resolution of sepsis. To assess whether additional contributions from myopathy, neuropathy and defects in neuromuscular transmission contributed to the reduction in force generation, we measured whole-muscle force production in response to electrical stimulation of the muscle nerve. We found no abnormality in force generation that would suggest the presence of myopathy, neuropathy or defective neuromuscular transmission. These data suggest disruption of repetitive firing of motor neurons is an important contributor to weakness induced by sepsis in rats and raise the possibility that reduced motor neuron excitability contributes to disability that persists after resolution of sepsis. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of acidic pH on voltage-gated ion channels in rat trigeminal mesencephalic nucleus neurons.

PubMed

Han, Jin-Eon; Cho, Jin-Hwa; Choi, In-Sun; Kim, Do-Yeon; Jang, Il-Sung

2017-03-01

The effects of acidic pH on several voltage-dependent ion channels, such as voltage-dependent K + and Ca 2+ channels, and hyperpolarization-gated and cyclic nucleotide-activated cation (HCN) channels, were examined using a whole-cell patch clamp technique on mechanically isolated rat mesencephalic trigeminal nucleus neurons. The application of a pH 6.5 solution had no effect on the peak amplitude of voltage-dependent K + currents. A pH 6.0 solution slightly, but significantly inhibited the peak amplitude of voltage-dependent K + currents. The pH 6.0 also shifted both the current-voltage and conductance-voltage relationships to the depolarization range. The application of a pH 6.5 solution scarcely affected the peak amplitude of membrane currents mediated by HCN channels, which were profoundly inhibited by the general HCN channel blocker Cs + (1 mM). However, the pH 6.0 solution slightly, but significantly inhibited the peak amplitude of HCN-mediated currents. Although the pH 6.0 solution showed complex modulation of the current-voltage and conductance-voltage relationships, the midpoint voltages for the activation of HCN channels were not changed by acidic pH. On the other hand, voltage-dependent Ca 2+ channels were significantly inhibited by an acidic pH. The application of an acidic pH solution significantly shifted the current-voltage and conductance-voltage relationships to the depolarization range. The modulation of several voltage-dependent ion channels by an acidic pH might affect the excitability of mesencephalic trigeminal nucleus neurons, and thus physiological functions mediated by the mesencephalic trigeminal nucleus could be affected in acidic pH conditions.

First wall for polarized fusion reactors

DOEpatents

Greenside, Henry S.; Budny, Robert V.; Post, Jr., Douglass E.

1988-01-01

Depolarization mechanisms arising from the recycling of the polarized fuel at the limiter and the first-wall of a fusion reactor are greater than those mechanisms in the plasma. Rapid depolarization of the plasma is prevented by providing a first-wall or first-wall coating formed of a low-Z, non-metallic material having a depolarization rate greater than 1 sec.sup.-1.

B cell activation. III. B cell plasma membrane depolarization and hyper- Ia antigen expression induced by receptor immunoglobulin cross-linking are coupled

PubMed Central

1983-01-01

We report investigation of the relationship between ligand-induced B cell plasma membrane depolarization and increased expression of membrane-associated, I-A subregion encoded (mI-A) antigens. Results demonstrate that equal frequencies of B cells are stimulated to undergo membrane depolarization and to increase mI-A expression in response to mitogen, anti-Ig, and thymus-independent (TI) or thymus-dependent (TD) antigens. Further, a cause-and-effect relationship between these two events is suggested by results that demonstrate that inhibition of anti- Fab--induced depolarization by valinomycin also inhibits the subsequent increase in mI-A antigen expression and "passive" (non-ligand-mediated) depolarization of murine B cells by K+ results in hyper-mI-A antigen expression. Based upon these results we hypothesize that antigen- mediated receptor cross-linking results in signal transduction via membrane depolarization, which is resultant in increased mI-A antigen synthesis and cell surface expression. This increase in mI-A antigen density may render the B cell more receptive to subsequent interaction with I-region-restricted helper T cells. PMID:6415207

Bi0.5Na0.5TiO3:ZnO lead-free piezoelectric composites with deferred thermal depolarization

NASA Astrophysics Data System (ADS)

Zhang, Ji; Pan, Zhao; Nie, Peng-Xiao; Cui, Yu-Shuang; Yang, Bin; Chen, Jun; Zhang, Shan-Tao

2015-06-01

Bi0.5Na0.5TiO3 (BNT) is among the most promising lead-free piezoelectric candidates. However, depolarization of BNT is a longstanding obstacle for practical applications. Here, we report that piezoelectric composites of Bi0.5Na0.5TiO3:xZnO (BNT:xZnO, where x is the mole ratio of ZnO to BNT) have deferred thermal depolarization. With increasing x from 0 to 0.4, the observed depolarization temperature (Td) tends to be deferred near x = 0.3, as confirmed by temperature dependent dielectric, ferroelectric, and piezoelectric measurements. As the result, the piezoelectric properties of the composites can be well maintained even after the poled composites are annealed at 125 °C. It is proposed that the charges stemming from ZnO can be orderly distributed to form a local field, which can keep the poling state of BNT, thus suppress the depolarization, even after the external poling filed is removed. These results may pave the way for applications of BNT-based piezoceramics and significantly improve our understanding of the depolarization mechanism by optimizing the performance of lead-free piezoelectrics.

Effect of positive pulse charge waveforms on the energy efficiency of lead-acid traction cells

NASA Technical Reports Server (NTRS)

Smithrick, J. J.

1981-01-01

The effects of four different charge methods on the energy conversion efficiency of 300 ampere hour lead acid traction cells were investigated. Three of the methods were positive pulse charge waveforms; the fourth, a constant current method, was used as a baseline of comparison. The positive pulse charge waveforms were: 120 Hz full wave rectified sinusoidal; 120 Hz silicon controlled rectified; and 1 kHz square wave. The constant current charger was set at the time average pulse current of each pulse waveform, which was 150 amps. The energy efficiency does not include charger losses. The lead acid traction cells were charged to 70 percent of rated ampere hour capacity in each case. The results of charging the cells using the three different pulse charge waveforms indicate there was no significant difference in energy conversion efficiency when compared to constant current charging at the time average pulse current value.

Investigation on Microstructure and Mechanical Properties of Continuous and Pulsed Current Gas Tungsten Arc Welded alloy 600

NASA Astrophysics Data System (ADS)

Srikanth, A.; Manikandan, M.

2018-02-01

The present study investigates the microstructure and mechanical properties of joints fabricated by Continuous and pulsed current gas tungsten arc welded alloy 600. Welding was done by autogenous mode. The macro examination was carried out to evaluate the welding defects in the weld joints. Optical and Scanning Electron Microscope (SEM) were performed to assess the microstructural changes in the fusion zone. Energy Dispersive Spectroscopy (EDS) analysis was carried to evaluate the microsegregation of alloying elements in the fusion zone. The tensile test was conducted to assess the strength of the weld joints. The results show that no welding defects were observed in the fusion zones of Continuous and Pulsed current Gas Tungsten Arc Welding. The refined microstructure was found in the pulsed current compared to continuous current mode. Microsegregation was not noticed in the weld grain boundary of continuous and pulsed current mode. The pulsed current shows improved mechanical properties compared to the continuous current mode.

Sodium leak channel, non-selective contributes to the leak current in human myometrial smooth muscle cells from pregnant women.

PubMed

Reinl, Erin L; Cabeza, Rafael; Gregory, Ismail A; Cahill, Alison G; England, Sarah K

2015-10-01

Uterine contractions are tightly regulated by the electrical activity of myometrial smooth muscle cells (MSMCs). These cells require a depolarizing current to initiate Ca(2+) influx and induce contraction. Cationic leak channels, which permit a steady flow of cations into a cell, are known to cause membrane depolarization in many tissue types. Previously, a Gd(3+)-sensitive, Na(+)-dependent leak current was identified in the rat myometrium, but the presence of such a current in human MSMCs and the specific ion channel conducting this current was unknown. Here, we report the presence of a Na(+)-dependent leak current in human myometrium and demonstrate that the Na(+)-leak channel, NALCN, contributes to this current. We performed whole-cell voltage-clamp on fresh and cultured MSMCs from uterine biopsies of term, non-laboring women and isolated the leak currents by using Ca(2+) and K(+) channel blockers in the bath solution. Ohmic leak currents were identified in freshly isolated and cultured MSMCs with normalized conductances of 14.6 pS/pF and 10.0 pS/pF, respectively. The myometrial leak current was significantly reduced (P < 0.01) by treating cells with 10 μM Gd(3+) or by superfusing the cells with a Na(+)-free extracellular solution. Reverse transcriptase PCR and immunoblot analysis of uterine biopsies from term, non-laboring women revealed NALCN messenger RNA and protein expression in the myometrium. Notably, ∼90% knockdown of NALCN protein expression with lentivirus-delivered shRNA reduced the Gd(3+)-sensitive leak current density by 42% (P < 0.05). Our results reveal that NALCN, in part, generates the leak current in MSMCs and provide the basis for future research assessing NALCN as a potential molecular target for modulating uterine excitability. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The Schizophrenia-Associated Kv11.1-3.1 Isoform Results in Reduced Current Accumulation during Repetitive Brief Depolarizations

PubMed Central

Heide, Juliane; Mann, Stefan A.; Vandenberg, Jamie I.

2012-01-01

Recent genome wide association studies identified a brain and primate specific isoform of a voltage-gated potassium channel, referred to as Kv11.1-3.1, which is significantly associated with schizophrenia. The 3.1 isoform replaces the first 102 amino acids of the most abundant isoform (referred to as Kv11.1-1A) with six unique amino acids. Here we show that the Kv11.1-3.1 isoform has faster rates of channel deactivation but a slowing of the rates of inactivation compared to the Kv11.1-1A isoform. The Kv11.1-3.1 isoform also has a significant depolarizing shift in the voltage-dependence of steady-state inactivation. The consequence of the altered gating kinetics is that there is lower current accumulation for Kv11.1-3.1 expressing cells during repetitive action potential firing compared to Kv11.1-1A expressing cells, which in turn will result in longer lasting trains of action potentials. Increased expression of Kv11.1-3.1 channels in the brain of schizophrenia patients might therefore contribute to disorganized neuronal firing. PMID:23029143

Isoflurane modulates neuronal excitability of the nucleus reticularis thalami in vitro.

PubMed

Joksovic, Pavle M; Todorovic, Slobodan M

2010-06-01

The thalamus has a key function in processing sensory information, sleep, and cognition. We examined the effects of a common volatile anesthetic, isoflurane, on modulation of neuronal excitability in reticular thalamic nucleus (nRT) in intact brain slices from immature rats. In current-clamp recordings, isoflurane (300-600 micromol/L) consistently depolarized membrane potential, decreased input resistance, and inhibited both rebound burst firing and tonic spike firing modes of nRT neurons. The isoflurane-induced depolarization persisted not only in the presence of tetrodotoxin, but after replacement of Ca(2+) with Ba(2+) ions in external solution; it was abolished by partial replacement of extracellular Na(+) ions with N-methyl-D-glucamine. In voltage-clamp recordings, we found that isoflurane slowed recovery from inactivation of T-type Ca(2+) current. Thus, at clinically relevant concentrations, isoflurane inhibits neuronal excitability of nRT neurons in developing brain via multiple ion channels. Inhibition of the neuronal excitability of thalamic cells may contribute to impairment of sensory information transfer in the thalamocortical network by general anesthetics. The findings may be important for understanding cellular mechanisms of anesthesia, such as loss of consciousness and potentially damaging consequences of general anesthetics on developing mammalian brains.

Influence of waveform and current direction on short-interval intracortical facilitation: a paired-pulse TMS study.

PubMed

Delvendahl, Igor; Lindemann, Hannes; Jung, Nikolai H; Pechmann, Astrid; Siebner, Hartwig R; Mall, Volker

2014-01-01

Transcranial magnetic stimulation (TMS) of the human primary motor hand area (M1-HAND) can produce multiple descending volleys in fast-conducting corticospinal neurons, especially so-called indirect waves (I-waves) resulting from trans-synaptic excitation. Facilitatory interaction between these I-waves can be studied non-invasively using a paired-pulse paradigm referred to as short-interval intracortical facilitation (SICF). We examined whether SICF depends on waveform and current direction of the TMS pulses. In young healthy volunteers, we applied single- and paired-pulse TMS to M1-HAND. We probed SICF by pairs of monophasic or half-sine pulses at suprathreshold stimulation intensity and inter-stimulus intervals (ISIs) between 1.0 and 5.0 ms. For monophasic paired-pulse stimulation, both pulses had either a posterior-anterior (PA) or anterior-posterior (AP) current direction (AP-AP or PA-PA), whereas current direction was reversed between first and second pulse for half-sine paired-pulse stimulation (PA-AP and AP-PA). Monophasic AP-AP stimulation resulted in stronger early SICF at 1.4 ms relative to late SICF at 2.8 and 4.4 ms, whereas monophasic PA-PA stimulation produced SICF of comparable size at all three peaks. With half-sine stimulation the third SICF peak was reduced for PA-AP current orientation compared with AP-PA. SICF elicited using monophasic as well as half-sine pulses is affected by current direction at clearly suprathreshold intensities. The impact of current orientation is stronger for monophasic compared with half-sine pulses. The direction-specific effect of paired-pulse TMS on the strength of early versus late SICF shows that different cortical circuits mediate early and late SICF. Copyright © 2014 Elsevier Inc. All rights reserved.

Possible effects of depolarizing GABAA conductance on the neuronal input-output relationship: a modeling study.

PubMed

Morita, Kenji; Tsumoto, Kunichika; Aihara, Kazuyuki

2005-06-01

Recent in vitro experiments revealed that the GABAA reversal potential is about 10 mV higher than the resting potential in mature mammalian neocortical pyramidal cells; thus GABAergic inputs could have facilitatory, rather than inhibitory, effects on action potential generation under certain conditions. However, how the relationship between excitatory input conductances and the output firing rate is modulated by such depolarizing GABAergic inputs under in vivo circumstances has not yet been understood. We examine herewith the input-output relationship in a simple conductance-based model of cortical neurons with the depolarized GABAA reversal potential, and show that a tonic depolarizing GABAergic conductance up to a certain amount does not change the relationship between a tonic glutamatergic driving conductance and the output firing rate, whereas a higher GABAergic conductance prevents spike generation. When the tonic glutamatergic and GABAergic conductances are replaced by in vivo-like highly fluctuating inputs, on the other hand, the effect of depolarizing GABAergic inputs on the input-output relationship critically depends on the degree of coincidence between glutamatergic input events and GABAergic ones. Although a wide range of depolarizing GABAergic inputs hardly changes the firing rate of a neuron driven by noncoincident glutamatergic inputs, a certain range of these inputs considerably decreases the firing rate if a large number of driving glutamatergic inputs are coincident with them. These results raise the possibility that the depolarized GABAA reversal potential is not a paradoxical mystery, but is instead a sophisticated device for discriminative firing rate modulation.

The role of entropic potential in voltage activation and K+ transport through Kv 1.2 channels

NASA Astrophysics Data System (ADS)

Wawrzkiewicz-Jałowiecka, Agata; Grzywna, Zbigniew J.

2018-03-01

We analyze the entropic effects of inner pore geometry changes of Kv 1.2 channel during membrane depolarization and their implications for the rate of transmembrane transport of potassium ions. We base this on the idea that spatial confinements within the channel pore give rise to entropic barriers which can both effectively affect the stability of open macroconformation and influence channel's ability to conduct the potassium ions through the membrane. First, we calculate the differences in entropy between voltage-activated and resting states of the channel. As a template, we take a set of structures of channel pore in an open state at different membrane potentials generated in our previous research. The obtained results indicate that tendency to occupy open states at membrane depolarization is entropy facilitated. Second, we describe the differences in rates of K+ transport through the channel pore at different voltages based on the results of appropriate random walk simulations in entropic and electric potentials. The simulated single channel currents (I) suggest that the geometry changes during membrane depolarization are an important factor contributing to the observed flow of potassium ions through the channel. Nevertheless, the charge distribution within the channel pore (especially at the extracellular entrance) seems most prominent for the observed I/Imax relation at a qualitative level at analyzed voltages.

The Potassium Channel, Kir3.4 Participates in Angiotensin II-Stimulated Aldosterone Production by a Human Adrenocortical Cell Line

PubMed Central

Oki, Kenji; Plonczynski, Maria W.; Lam, Milay Luis; Gomez-Sanchez, Elise P.

2012-01-01

Angiotensin II (A-II) regulation of aldosterone secretion is initiated by inducing cell membrane depolarization, thereby increasing intracellular calcium and activating the calcium calmodulin/calmodulin kinase cascade. Mutations in the selectivity filter of the KCNJ5 gene coding for inward rectifying potassium channel (Kir)3.4 has been found in about one third of aldosterone-producing adenomas. These mutations result in loss of selectivity of the inward rectifying current for potassium, which causes membrane depolarization and opening of calcium channels and activation of the calcium calmodulin/calmodulin kinase cascade and results in an increase in aldosterone secretion. In this study we show that A-II and a calcium ionophore down-regulate the expression of KCNJ5 mRNA and protein. Activation of Kir3.4 by naringin inhibits A-II-stimulated membrane voltage and aldosterone secretion. Overexpression of KCNJ5 in the HAC15 cells using a lentivirus resulted in a decrease in membrane voltage, intracellular calcium, expression of steroidogenic acute regulatory protein, 3-β-hydroxysteroid dehydrogenase 3B2, cytochrome P450 11B1 and cytochrome P450 11B2 mRNA, and aldosterone synthesis. In conclusion, A-II appears to stimulate aldosterone secretion by depolarizing the membrane acting in part through the regulation of the expression and activity of Kir3.4. PMID:22798349

Inward rectifier K+ channel and T-type Ca2+ channel contribute to enhancement of GABAergic transmission induced by β1-adrenoceptor in the prefrontal cortex.

PubMed

Luo, Fei; Zheng, Jian; Sun, Xuan; Tang, Hua

2017-02-01

The functions of prefrontal cortex (PFC) are sensitive to norepinephrine (NE). Endogenously released NE influences synaptic transmission through activation of different subtypes of adrenergic receptors in PFC including α 1 , α 2 , β 1 or β 2 -adrenoceptor. Our recent study has revealed that β 1 -adrenoceptor (β 1 -AR) activation modulates glutamatergic transmission in the PFC, whereas the roles of β 1 -AR in GABAergic transmission are elusive. In the current study, we probed the effects of the β 1 -AR agonist dobutamine (Dobu) on GABAergic transmission onto pyramidal neurons in the PFC of juvenile rats. Dobu increased both the frequency and amplitude of miniature IPSCs (mIPSCs). Ca 2+ influx through T-type voltage-gated Ca 2+ channel was required for Dobu-enhanced mIPSC frequency. We also found that Dobu facilitated GABA release probability and the number of releasable vesicles through regulating T-type Ca 2+ channel. Dobu depolarized GABAergic fast-spiking (FS) interneurons with no effects on the firing rate of action potentials (APs) of interneurons. Dobu-induced depolarization of FS interneurons required inward rectifier K + channel (Kir). Our results suggest that Dobu increase GABA release via inhibition of Kir, which further depolarizes FS interneurons resulting in Ca 2+ influx via T-type Ca 2+ channel. Copyright © 2016 Elsevier Inc. All rights reserved.

Contribution For Arc Temperature Affected By Current Increment Ratio At Peak Current In Pulsed Arc

NASA Astrophysics Data System (ADS)

Kano, Ryota; Mitubori, Hironori; Iwao, Toru

2015-11-01

Tungsten Inert Gas (TIG) Welding is one of the high quality welding. However, parameters of the pulsed arc welding are many and complicated. if the welding parameters are not appropriate, the welding pool shape becomes wide and shallow.the convection of driving force contributes to the welding pool shape. However, in the case of changing current waveform as the pulse high frequency TIG welding, the arc temperature does not follow the change of the current. Other result of the calculation, in particular, the arc temperature at the reaching time of peak current is based on these considerations. Thus, the accurate measurement of the temperature at the time is required. Therefore, the objective of this research is the elucidation of contribution for arc temperature affected by current increment ratio at peak current in pulsed arc. It should obtain a detail knowledge of the welding model in pulsed arc. The temperature in the case of increment of the peak current from the base current is measured by using spectroscopy. As a result, when the arc current increases from 100 A to 150 A at 120 ms, the transient response of the temperature didn't occur during increasing current. Thus, during the current rise, it has been verified by measuring. Therefore, the contribution for arc temperature affected by current increment ratio at peak current in pulsed arc was elucidated in order to obtain more knowledge of welding model of pulsed arc.

Comment on ``Quasiperiodic spin-orbit motion and spin tunes in storage rings''

NASA Astrophysics Data System (ADS)

Lee, S. Y.; Mane, S. R.

2005-08-01

Contrary to the claim of the recent publication by Barber, Ellison, and Heinemann [Phys. Rev. ST Accel. Beams, PRABFM, 1098-4402 7, 124002 (2004)., 10.1103/PhysRevSTAB.7.124002], we explain in this Comment that (1) the snake resonances are spin depolarizing resonances just like other spin depolarizing resonances and (2) the perturbed spin tune is useful to understand depolarization phenomena.

Sarcoplasmic reticulum Ca2+ permeation explored from the lumen side in mdx muscle fibers under voltage control

PubMed Central

Robin, Gaëlle; Berthier, Christine

2012-01-01

Under resting conditions, external Ca2+ is known to enter skeletal muscle cells, whereas Ca2+ stored in the sarcoplasmic reticulum (SR) leaks into the cytosol. The nature of the pathways involved in the sarcolemmal Ca2+ entry and in the SR Ca2+ leak is still a matter of debate, but several lines of evidence suggest that these Ca2+ fluxes are up-regulated in Duchenne muscular dystrophy. We investigated here SR calcium permeation at resting potential and in response to depolarization in voltage-controlled skeletal muscle fibers from control and mdx mice, the mouse model of Duchenne muscular dystrophy. Using the cytosolic Ca2+ dye Fura2, we first demonstrated that the rate of Ca2+ increase in response to cyclopiazonic acid (CPA)–induced inhibition of SR Ca2+-ATPases at resting potential was significantly higher in mdx fibers, which suggests an elevated SR Ca2+ leak. However, removal of external Ca2+ reduced the rate of CPA-induced Ca2+ increase in mdx and increased it in control fibers, which indicates an up-regulation of sarcolemmal Ca2+ influx in mdx fibers. Fibers were then loaded with the low-affinity Ca2+ dye Fluo5N-AM to measure intraluminal SR Ca2+ changes. Trains of action potentials, chloro-m-cresol, and depolarization pulses evoked transient Fluo5N fluorescence decreases, and recovery of voltage-induced Fluo5N fluorescence changes were inhibited by CPA, demonstrating that Fluo5N actually reports intraluminal SR Ca2+ changes. Voltage dependence and magnitude of depolarization-induced SR Ca2+ depletion were found to be unchanged in mdx fibers, but the rate of the recovery phase that followed depletion was found to be faster, indicating a higher SR Ca2+ reuptake activity in mdx fibers. Overall, CPA-induced SR Ca2+ leak at −80 mV was found to be significantly higher in mdx fibers and was potentiated by removal of external Ca2+ in control fibers. The elevated passive SR Ca2+ leak may contribute to alteration of Ca2+ homeostasis in mdx muscle. PMID:22371362

Depolarization Alters Phenotype, Maintains Plasticity of Predifferentiated Mesenchymal Stem Cells

PubMed Central

Sundelacruz, Sarah; Levin, Michael

2013-01-01

Although adult stem cell transplantation has been implemented as a therapy for tissue repair, it is limited by the availability of functional adult stem cells. A potential approach to generate stem and progenitor cells may be to modulate the differentiated status of somatic cells. Therefore, there is a need for a better understanding of how the differentiated phenotype of mature cells is regulated. We hypothesize that bioelectric signaling plays an important role in the maintenance of the differentiated state, as it is a functional regulator of the differentiation process in various cells and tissues. In this study, we asked whether the mature phenotype of osteoblasts and adipocytes derived from human mesenchymal stem cells (hMSCs) could be altered by modulation of their membrane potential. hMSC-derived osteoblasts and adipocytes were depolarized by treatment with ouabain, a Na+/K+ ATPase inhibitor, or by treatment with high concentrations of extracellular K+. To characterize the effect of voltage modulation on the differentiated state, the depolarized cells were evaluated for (1) the loss of differentiation markers; (2) the up-regulation of stemness markers and stem properties; and (3) differences in gene expression profiles in response to voltage modulation. hMSC-derived osteoblasts and adipocytes exhibited significant down-regulation of bone and fat tissue markers in response to depolarization, despite the presence of differentiation-inducing soluble factors, suggesting that bioelectric signaling overrides biochemical signaling in the maintenance of cell state. Suppression of the osteoblast or adipocyte phenotype was not accompanied by up-regulation of genes associated with the stem state. Thus, depolarization does not activate the stem cell genetic signature and, therefore, does not induce a full reprogramming event. However, after transdifferentiating the depolarized cells to evaluate for multi-lineage potential, depolarized osteoblasts demonstrated improved ability to achieve correct adipocyte morphology compared with nondepolarized osteoblasts. The present study thus demonstrates that depolarization reduces the differentiated phenotype of hMSC-derived cells and improves their transdifferentiation capacity, but does not restore a stem-like genetic profile. Through global transcript profiling of depolarized osteoblasts, we identified pathways that may mediate the effects of voltage signaling on cell state, which will require a detailed mechanistic inquiry in future studies. PMID:23738690

Novel high-frequency energy-efficient pulsed-dc generator for capacitively coupled plasma discharge

NASA Astrophysics Data System (ADS)

Mamun, Md Abdullah Al; Furuta, Hiroshi; Hatta, Akimitsu

2018-03-01

The circuit design, assembly, and operating tests of a high-frequency and high-voltage (HV) pulsed dc generator (PDG) for capacitively coupled plasma (CCP) discharge inside a vacuum chamber are reported. For capacitive loads, it is challenging to obtain sharp rectangular pulses with fast rising and falling edges, requiring intense current for quick charging and discharging. The requirement of intense current generally limits the pulse operation frequency. In this study, we present a new type of PDG consisting of a pair of half-resonant converters and a constant current-controller circuit connected with HV solid-state power switches that can deliver almost rectangular high voltage pulses with fast rising and falling edges for CCP discharge. A prototype of the PDG is assembled to modulate from a high-voltage direct current (HVdc) input into a pulsed HVdc output, while following an input pulse signal and a set current level. The pulse rise time and fall time are less than 500 ns and 800 ns, respectively, and the minimum pulse width is 1 µs. The maximum voltage for a negative pulse is 1000 V, and the maximum repetition frequency is 500 kHz. During the pulse on time, the plasma discharge current is controlled steadily at the set value. The half-resonant converters in the PDG perform recovery of the remaining energy from the capacitive load at every termination of pulse discharge. The PDG performed with a high energy efficiency of 85% from the HVdc input to the pulsed dc output at a repetition rate of 1 kHz and with stable plasma operation in various discharge conditions. The results suggest that the developed PDG can be considered to be more efficient for plasma processing by CCP.

Novel high-frequency energy-efficient pulsed-dc generator for capacitively coupled plasma discharge.

PubMed

Mamun, Md Abdullah Al; Furuta, Hiroshi; Hatta, Akimitsu

2018-03-01

The circuit design, assembly, and operating tests of a high-frequency and high-voltage (HV) pulsed dc generator (PDG) for capacitively coupled plasma (CCP) discharge inside a vacuum chamber are reported. For capacitive loads, it is challenging to obtain sharp rectangular pulses with fast rising and falling edges, requiring intense current for quick charging and discharging. The requirement of intense current generally limits the pulse operation frequency. In this study, we present a new type of PDG consisting of a pair of half-resonant converters and a constant current-controller circuit connected with HV solid-state power switches that can deliver almost rectangular high voltage pulses with fast rising and falling edges for CCP discharge. A prototype of the PDG is assembled to modulate from a high-voltage direct current (HVdc) input into a pulsed HVdc output, while following an input pulse signal and a set current level. The pulse rise time and fall time are less than 500 ns and 800 ns, respectively, and the minimum pulse width is 1 µs. The maximum voltage for a negative pulse is 1000 V, and the maximum repetition frequency is 500 kHz. During the pulse on time, the plasma discharge current is controlled steadily at the set value. The half-resonant converters in the PDG perform recovery of the remaining energy from the capacitive load at every termination of pulse discharge. The PDG performed with a high energy efficiency of 85% from the HVdc input to the pulsed dc output at a repetition rate of 1 kHz and with stable plasma operation in various discharge conditions. The results suggest that the developed PDG can be considered to be more efficient for plasma processing by CCP.

Eye Safe, Visible Wavelength Lidar Systems: Design and Operational Advances, Results and Potential

NASA Technical Reports Server (NTRS)

Spinhirne, James; Welton, Ellsworth J.; Berkoff, Timothy; Campbell, James

2007-01-01

In the early nineties the first of the eye safe visible wavelength lidar systems known now as Micro Pulse Lidar (MPL) became operational. The important advance of the design was a system that, unlike most existing lidar, operated at eye safe energy densities and could thus operate unattended for full time monitoring. Since that time there have been many dozens of these systems produced and applied for full time profiling of atmospheric cloud and aerosol structure. There is currently an observational network of MPL sites to support global climate research. In thc course of application of these instruments there have been significant improvements in the, design and performance of the systems. In the last half decade particularly there has been significant application and technical development of MPL systems. In this paper we review progress. The current MPL systems in use are all single wavelength systems designed for cloud and aerosol applications. For the cloud and aerosol applications, both lidar depolarization and multi wavelength measurements have significant applications. These can be accomplished with the MPL, approach. The main current challenge for the lidar network activity are in the area of the reliability, repeatability and efficiency of data processing. The network makes use of internet data downloads and automated processing. The heights of all cloud and aerosol layers are needed. The recent emphasis has been in operationally deriving aerosol extinction cross section. Future emphasis will include adding cirrus optical parameters. For operational effectiveness, improvements to simplify routine data signal calibration are being researched. Overall the MPL systems have proven very effective. A large data base of results from globally distributed sites can be easily accessed through the internet. Applications have included atmospheric model development. Validation of current global satellite observations of aerosol and clouds, including now orbital lidar observations, was a primary goal for NASA. Although sampling issues require careful consideration, results have proven useful.

Transformer miniaturization for transcutaneous current/voltage pulse applications.

PubMed

Kolen, P T

1999-05-01

A general procedure for the design of a miniaturized step up transformer to be used in the context of surface electrode based current/voltage pulse generation is presented. It has been shown that the optimum secondary current pulse width is 4.5 tau, where tau is the time constant associated with the pulse forming network associated with the transformer/electrode interaction. This criteria has been shown to produce the highest peak to average current ratio for the secondary current pulse. The design procedure allows for the calculation of the optimum turns ratio, primary turns, and secondary turns for a given electrode load/tissue and magnetic core parameters. Two design examples for transformer optimization are presented.

Effect of Mg2+ on the control of Ca2+ release in skeletal muscle fibres of the toad.

PubMed Central

Lamb, G D; Stephenson, D G

1991-01-01

1. The effect of myoplasmic Mg2+ on Ca2+ release was examined in mechanically skinned skeletal muscle fibres, in which the normal voltage-sensor control of Ca2+ release is preserved. The voltage sensors could be activated by depolarizing the transverse tubular (T-) system by lowering the [K+] in the bathing solution. 2. Fibres spontaneously contracted when the free [Mg2+] was decreased from 1 to 0.05 mM, with no depolarization or change of total ATP, [Ca2+] or pH (pCa 6.7, 50 microM-EGTA). After such a 'low-Mg2+ response' the sarcoplasmic reticulum (SR) was depleted of Ca2+ and neither depolarization nor caffeine (2 mM) could induce a response, unless the [Mg2+] was raised and the SR reloaded with Ca2+. Exposure to 0.05 mM-Mg2+ at low [Ca2+] (2 mM-free EGTA, pCa greater than 8.7) also induced Ca2+ release and depleted the SR. 3. The response to low [Mg2+] was unaffected by inactivation of the voltage sensors, but was completely blocked by 2 microM-Ruthenium Red indicating that it involved Ca2+ efflux through the normal Ca2+ release channels. 4. In the absence of ATP (and creatine phosphate), complete removal of Mg2+ (i.e. no added Mg2+ with 1 mM-EDTA) did not induce Ca2+ release. Depolarization in the absence of Mg2+ and ATP also did not induce Ca2+ release. 5. Depolarization in 10 mM-Mg2+ (pCa 6.7, 50 microM-EGTA, 8 mM-total ATP) did not produce any response. In the presence of 1 mM-EGTA to chelate most of the released Ca2+, depolarizations in 10 mM-Mg2+ did not noticeably deplete the SR of Ca2+, whereas a single depolarization in 1 mM-Mg2+ (and 1 mM-EGTA) resulted in marked depletion. Depolarization in the presence of D600 and 10 mM-Mg2+ produced use-dependent 'paralysis', indicating that depolarization in 10 mM-Mg2+ did indeed activate the voltage sensors. 6. Depolarization in the presence of 10 mM-Mg2+ and 25 microM-ryanodine neither interfered with the normal voltage control of Ca2+ release nor caused depletion of the Ca2+ in the SR even after returning to 1 mM-Mg2+ for 1 min, indicating that few if any of the release channels had been opened by the depolarization.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:1708823

Optimization of Experimental Conditions of the Pulsed Current GTAW Parameters for Mechanical Properties of SDSS UNS S32760 Welds Based on the Taguchi Design Method

NASA Astrophysics Data System (ADS)

Yousefieh, M.; Shamanian, M.; Saatchi, A.

2012-09-01

Taguchi design method with L9 orthogonal array was implemented to optimize the pulsed current gas tungsten arc welding parameters for the hardness and the toughness of super duplex stainless steel (SDSS, UNS S32760) welds. In this regard, the hardness and the toughness were considered as performance characteristics. Pulse current, background current, % on time, and pulse frequency were chosen as main parameters. Each parameter was varied at three different levels. As a result of pooled analysis of variance, the pulse current is found to be the most significant factor for both the hardness and the toughness of SDSS welds by percentage contribution of 71.81 for hardness and 78.18 for toughness. The % on time (21.99%) and the background current (17.81%) had also the next most significant effect on the hardness and the toughness, respectively. The optimum conditions within the selected parameter values for hardness were found as the first level of pulse current (100 A), third level of background current (70 A), first level of % on time (40%), and first level of pulse frequency (1 Hz), while they were found as the second level of pulse current (120 A), second level of background current (60 A), second level of % on time (60%), and third level of pulse frequency (5 Hz) for toughness. The Taguchi method was found to be a promising tool to obtain the optimum conditions for such studies. Finally, in order to verify experimental results, confirmation tests were carried out at optimum working conditions. Under these conditions, there were good agreements between the predicted and the experimental results for the both hardness and toughness.

Permethrin enhances the agonist activity of dinotefuran on insect cholinergic synaptic transmission and isolated neurons.

PubMed

Cartereau, Alison; Houchat, Jean-Noël; Mannai, Safa; Varloud, Marie; Karembé, Hamadi; Graton, Jérôme; Le Questel, Jean-Yves; Thany, Steeve H

2018-06-08

Insect resistance mechanisms against pesticides lead to the development and the search of new pesticide combinations in order to delay the resistance. The combination of neonicotinoids with pyrethroids was currently proposed but the mode of action of these compounds at synaptic and extrasynaptic levels needs to be further explored. In the present study, we evaluated the effect of the combination of two insecticides, permethrin and dinotefuran, on cockroach cholinergic synaptic transmission and on isolated cell bodies. We first found that combination of 5 μM permethrin and dinotefuran enhances depolarization of the sixth abdominal ganglion compared to dinotefuran alone, without an inhibition of the spontaneous activity. However, a pretreatment with 1 μM dinotefuran or permethrin before bath application of the mixture inhibits the ganglionic depolarization. Compared to permethrin, 1 μM dinotefuran induces a persistent enhancement of spontaneous activity. Interestingly, at extrasynaptic level, using dorsal unpaired median neurons and Kenyon cells, we found that combination of both 1 μM dinotefuran and permethrin resulted in an increase of the mixture-induced current amplitudes. Pretreatment with 1 μM dinotefuran strongly decreases the currents whereas permethrin induces a time-dependent inhibition. These data demonstrate that the combination of dinotefuran and permethrin enhances the effect of dinotefuran. Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.

Chloride equilibrium potential in salamander cones

PubMed Central

Thoreson, Wallace B; Bryson, Eric J

2004-01-01

Background GABAergic inhibition and effects of intracellular chloride ions on calcium channel activity have been proposed to regulate neurotransmission from photoreceptors. To assess the impact of these and other chloride-dependent mechanisms on release from cones, the chloride equilibrium potential (ECl) was determined in red-sensitive, large single cones from the tiger salamander retinal slice. Results Whole cell recordings were done using gramicidin perforated patch techniques to maintain endogenous Cl- levels. Membrane potentials were corrected for liquid junction potentials. Cone resting potentials were found to average -46 mV. To measure ECl, we applied long depolarizing steps to activate the calcium-activated chloride current (ICl(Ca)) and then determined the reversal potential for the current component that was inhibited by the Cl- channel blocker, niflumic acid. With this method, ECl was found to average -46 mV. In a complementary approach, we used a Cl-sensitive dye, MEQ, to measure the Cl- flux produced by depolarization with elevated concentrations of K+. The membrane potentials produced by the various high K+ solutions were measured in separate current clamp experiments. Consistent with electrophysiological experiments, MEQ fluorescence measurements indicated that ECl was below -36 mV. Conclusions The results of this study indicate that ECl is close to the dark resting potential. This will minimize the impact of chloride-dependent presynaptic mechanisms in cone terminals involving GABAa receptors, glutamate transporters and ICl(Ca). PMID:15579212

Biophysically Based Mathematical Modeling of Interstitial Cells of Cajal Slow Wave Activity Generated from a Discrete Unitary Potential Basis

PubMed Central

Faville, R.A.; Pullan, A.J.; Sanders, K.M.; Koh, S.D.; Lloyd, C.M.; Smith, N.P.

2009-01-01

Abstract Spontaneously rhythmic pacemaker activity produced by interstitial cells of Cajal (ICC) is the result of the entrainment of unitary potential depolarizations generated at intracellular sites termed pacemaker units. In this study, we present a mathematical modeling framework that quantitatively represents the transmembrane ion flows and intracellular Ca2+ dynamics from a single ICC operating over the physiological membrane potential range. The mathematical model presented here extends our recently developed biophysically based pacemaker unit modeling framework by including mechanisms necessary for coordinating unitary potential events, such as a T-Type Ca2+ current, Vm-dependent K+ currents, and global Ca2+ diffusion. Model simulations produce spontaneously rhythmic slow wave depolarizations with an amplitude of 65 mV at a frequency of 17.4 cpm. Our model predicts that activity at the spatial scale of the pacemaker unit is fundamental for ICC slow wave generation, and Ca2+ influx from activation of the T-Type Ca2+ current is required for unitary potential entrainment. These results suggest that intracellular Ca2+ levels, particularly in the region local to the mitochondria and endoplasmic reticulum, significantly influence pacing frequency and synchronization of pacemaker unit discharge. Moreover, numerical investigations show that our ICC model is capable of qualitatively replicating a wide range of experimental observations. PMID:19527643

Connexin43 contributes to electrotonic conduction across scar tissue in the intact heart

NASA Astrophysics Data System (ADS)

Mahoney, Vanessa M.; Mezzano, Valeria; Mirams, Gary R.; Maass, Karen; Li, Zhen; Cerrone, Marina; Vasquez, Carolina; Bapat, Aneesh; Delmar, Mario; Morley, Gregory E.

2016-05-01

Studies have demonstrated non-myocytes, including fibroblasts, can electrically couple to myocytes in culture. However, evidence demonstrating current can passively spread across scar tissue in the intact heart remains elusive. We hypothesize electrotonic conduction occurs across non-myocyte gaps in the heart and is partly mediated by Connexin43 (Cx43). We investigated whether non-myocytes in ventricular scar tissue are electrically connected to surrounding myocardial tissue in wild type and fibroblast-specific protein-1 driven conditional Cx43 knock-out mice (Cx43fsp1KO). Electrical coupling between the scar and uninjured myocardium was demonstrated by injecting current into the myocardium and recording depolarization in the scar through optical mapping. Coupling was significantly reduced in Cx43fsp1KO hearts. Voltage signals were recorded using microelectrodes from control scars but no signals were obtained from Cx43fsp1KO hearts. Recordings showed significantly decreased amplitude, depolarized resting membrane potential, increased duration and reduced upstroke velocity compared to surrounding myocytes, suggesting that the non-excitable cells in the scar closely follow myocyte action potentials. These results were further validated by mathematical simulations. Optical mapping demonstrated that current delivered within the scar could induce activation of the surrounding myocardium. These data demonstrate non-myocytes in the scar are electrically coupled to myocytes, and coupling depends on Cx43 expression.

Interaction between depolarization effects, interface layer, and fatigue behavior in PZT thin film capacitors

NASA Astrophysics Data System (ADS)

Böttger, U.; Waser, R.

2017-07-01

The existence of non-ferroelectric regions in ferroelectric thin films evokes depolarization effects leading to a tilt of the P(E) hysteresis loop. The analysis of measured hysteresis of lead zirconate titanate (PZT) thin films is used to determine a depolarization factor which contains quantitative information about interfacial layers as well as ferroelectrically passive zones in the bulk. The derived interfacial capacitance is smaller than that estimated from conventional extrapolation techniques. In addition, the concept of depolarization is used for the investigation of fatigue behavior of PZT thin films indicating that the mechanism of seed inhibition, which is responsible for the effect, occurs in the entire film.

Diagnosis and Treatment of Fetal Arrhythmia

PubMed Central

Wacker-Gussmann, Annette; Strasburger, Janette F.; Cuneo, Bettina F.; Wakai, Ronald T.

2014-01-01

Detection and careful stratification of fetal heart rate (FHR) is extremely important in all pregnancies. The most lethal cardiac rhythm disturbances occur during apparently normal pregnancies where FHR and rhythmare regular and within normal or low-normal ranges. These hidden depolarization and repolarization abnormalities, associated with genetic ion channelopathies cannot be detected by echocardiography, and may be responsible for up to 10% of unexplained fetal demise, prompting a need for newer and better fetal diagnostic techniques. Other manifest fetal arrhythmias such as premature beats, tachycardia, and bradycardia are commonly recognized. Heart rhythm diagnosis in obstetrical practice is usually made by M-mode and pulsed Doppler fetal echocardiography, but not all fetal cardiac time intervals are captured by echocardiographic methods. This article reviews different types of fetal arrhythmias, their presentation and treatment strategies, and gives an overview of the present and future diagnostic techniques. PMID:24858320

Time-resolved stimulated emission depletion and energy transfer dynamics in two-photon excited EGFP.

PubMed

Masters, T A; Robinson, N A; Marsh, R J; Blacker, T S; Armoogum, D A; Larijani, B; Bain, A J

2018-04-07

Time and polarization-resolved stimulated emission depletion (STED) measurements are used to investigate excited state evolution following the two-photon excitation of enhanced green fluorescent protein (EGFP). We employ a new approach for the accurate STED measurement of the hitherto unmeasured degree of hexadecapolar transition dipole moment alignment α 40 present at a given excitation-depletion (pump-dump) pulse separation. Time-resolved polarized fluorescence measurements as a function of pump-dump delay reveal the time evolution of α 40 to be considerably more rapid than predicted for isotropic rotational diffusion in EGFP. Additional depolarization by homo-Förster resonance energy transfer is investigated for both α 20 (quadrupolar) and α 40 transition dipole alignments. These results point to the utility of higher order dipole correlation measurements in the investigation of resonance energy transfer processes.

Auditory thresholds in the American cockroach (Orthoptera: Blattidae): estimates using single-unit and compound-action potential recordings.

PubMed

Decker, T N; Jones, T A; Gold, R E

1989-06-01

Recent commercial suggestions that insect populations can be controlled through the use of ultrasound raises the question of whether or not certain insects have receptors that are sensitive to high-frequency sound. Single neural unit discharges and compound-action potentials were recorded from the ventral nerve cord in the American cockroach, Periplaneta americana L., to constant rise time tone pulses from 100 to 40,000 hertz (Hz). Unit responses and compound-action potentials show that the cockroach is insensitive to sound above approximately 3,000 Hz. Data relating latency of the response to intensity of the stimulus suggest that the cockroach cercal system operates on the principle of energy envelope detection. Decreases in latency likely occur primarily as a result of increases in the rate of membrane depolarization in cercal dendrites.

Spontaneous sarcoplasmic reticulum calcium release and extrusion from bovine, not porcine, coronary artery smooth muscle.

PubMed Central

Stehno-Bittel, L; Sturek, M

1992-01-01

1. We tested the hypothesis that the Ca(2+)-loaded sarcoplasmic reticulum (SR) of coronary artery smooth muscle spontaneously releases Ca2+ preferentially toward the sarcolemma to be extruded from the cell without increasing the average free myoplasmic [Ca2+] (Ca(im)) concentration. 2. The SR of bovine cells was Ca(2+)-loaded by depolarization-induced Ca2+ influx. Release (unloading) of Ca2+ from the SR during recovery from depolarization was determined by Fura-2 microfluorometry of Ca(im). The SR Ca2+ unloading was maximal following a long (14 min) recovery from depolarization, as shown by the 66% decrease in the peak caffeine-induced Ca(im) transient compared to the Ca(im) transient after a short (2 min) recovery. No increase in Ca(im) occurred during the long recovery. No unloading of the SR Ca2+ store was noted in porcine cells. 3. Approximately 80% of the outward K+ current in bovine and porcine cells was sensitive to subsarcolemmal Ca2+ (Ca(is)) concentrations. Whole-cell voltage clamp using pipette solutions with Ca2+ concentrations clamped between 0 and 1000 nM with Ca(2+)-EGTA or Ca(2+)-BAPTA buffers showed increasing K+ currents (normalized for cell membrane surface area) as a function of both membrane potential and Ca(is). Clamping of Ca(im) and Ca(is) was verified by the lack of changes in K+ current and Fura-2 ratio in response to Ca2+ influx, Ca(2+)-free external solution, or caffeine-induced Ca2+ release. At +30 to +50 mV the K+ current amplitude showed a similar sensitivity to Ca2+ as Fura-2. These data indicate that in this experimental preparation Ca(2+)-activated K+ current is a valid estimate of Ca(is). 4. Simultaneous Ca(im) and Ca(is) measurements in bovine cells which were not Ca(2+)-clamped (2 x 10(-4) M-EGTA pipette solution) showed that during the long recovery period the K+ current (reflecting Ca(is)) increased 55%, while Ca(im) did not change. 5. In quiescent bovine cells the Ca(is) was higher than Ca(im), while the higher resting Ca(is) gradient was not apparent in porcine cells. 6. The Ca(is) concentration was directly related to the amount of Ca2+ in the SR in bovine, but not porcine cells. Depletion of the SR in bovine cells by caffeine resulted in a 58% decrease in K+ current compared to the resting K+ current. 7. Caffeine-induced Ca2+ release caused an increase in Ca(is) which preceded the increase in Ca(im) by approximately 2 s.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:1403820

Direct block of inward rectifier potassium channels by nicotine.

PubMed

Wang, H; Yang, B; Zhang, L; Xu, D; Wang, Z

2000-04-01

Nicotine has been shown to depolarize membrane potential and to lengthen action potential duration in isolated cardiac preparations. To investigate whether this is a consequence of direct interaction of nicotine with inward rectifier K(+) channels which are a key determinant of membrane potentials, we assessed the effects of nicotine on two cloned human inward rectifier K(+) channels, Kir2.1 and Kir2.2, expressed in Xenopus oocytes and the native inward rectifier K(+) current I(K1) in canine ventricular myocytes. Nicotine suppressed Kir2.1-expressed currents at varying potentials negative to -20 mV, with more pronounced effects on the outward current between -70 and -20 mV relative to the inward current at hyperpolarized potentials (below -70 mV). The inhibition was concentration dependent. For the outward currents recorded at -50 mV, the IC50 was 165 +/- 18 microM. Similar effects of nicotine were observed for Kir2.2. A more potent effect was seen with I(K1) in canine myocytes. Significant blockade ( approximately 60%) was found at a concentration as low as 0.5 microM and the IC50 was 4.0 +/- 0.4 microM. The effects in both oocytes and myocytes were partially reversible upon washout of nicotine. Antagonists of nicotinic receptors (mecamylamine, 100 microM), muscarinic receptors (atropine, 1 microM), and beta-adrenergic receptors (propranolol, 1 microM) all failed to restore the depressed currents, suggesting that nicotine acted directly on Kir channels, independent of catecholamine release. This property of nicotine may explain its membrane-depolarizing and action potential duration-prolonging effects in cardiac cells and may contribute in part to its ability to promote propensity for cardiac arrhythmias. Copyright 2000 Academic Press.

Serotonin regulates voltage-dependent currents in type Ie(A) and Ii interneurons of Hermissenda

PubMed Central

Jin, Nan Ge

2011-01-01

Serotonin (5-HT) has both direct and modulatory actions on central neurons contributing to behavioral arousal and cellular-synaptic plasticity in diverse species. In Hermissenda, 5-HT produces changes in intrinsic excitability of different types of identified interneurons in the circumesophageal nervous system. Using whole cell patch-clamp techniques we have examined membrane conductance changes produced by 5-HT that contribute to intrinsic excitability in two identified classes of interneurons, types Ii and IeA. Whole cell currents were examined before and after 5-HT application to the isolated nervous system. A 4-aminopyridine-sensitive transient outward K+ current [IK(A)], a tetraethylammonium-sensitive delayed rectifier K+ current [IK(V)], an inward rectifier K+ current [IK(IR)], and a hyperpolarization-activated current (Ih) were characterized. 5-HT decreased the amplitude of IK(A) and IK(V) in both type Ii and IeA interneurons. However, differences in 5-HT's effects on the activation-inactivation kinetics were observed in different types of interneurons. 5-HT produced a depolarizing shift in the activation curve of IK(V) and a hyperpolarizing shift in the inactivation curve of IK(A) in type Ii interneurons. In contrast, 5-HT produced a depolarizing shift in the activation curve and a hyperpolarizing shift in the inactivation curve of both IK(V) and IK(A) in type IeA interneurons. In addition, 5-HT decreased the amplitude of IK(IR) in type Ii interneurons and increased the amplitude of Ih in type IeA interneurons. These results indicate that 5-HT-dependent changes in IK(A), IK(V), IK(IR), and Ih contribute to multiple mechanisms that synergistically support modulation of increased intrinsic excitability associated with different functional classes of identified type I interneurons. PMID:21813747

Cellular and synaptic effect of substance P on neonatal phrenic motoneurons.

PubMed

Ptak, K; Konrad, M; Di Pasquale, E; Tell, F; Hilaire, G; Monteau, R

2000-01-01

Experiments were carried out on the in vitro brainstem-spinal cord preparation of the newborn rat to analyse the effects of substance P (SP) on phrenic motoneuron (PMN) activity. In current-clamp mode, SP significantly depolarized PMNs, increased their input resistance, decreased the rheobase current and shifted the firing frequency-intensity relationships leftwards, but did not affect spike frequency adaptation or single spike configuration. The neurokinin receptor agonist NK1 had SP-mimetic effects, whereas the NK3 and NK2 receptor agonists were less effective and ineffective, respectively. In a tetrodotoxin-containing aCSF, only SP or the NK1 receptor agonist were still active. No depolarization was observed when the NK1 receptor agonist was applied in the presence of muscarine. In voltage-clamp mode, SP or the NK1 receptor agonist produced an inward current (ISP) which was not significantly reduced by extracellular application of tetraethylammonium, Co2+, 4-aminopyridine or Cs+. In aCSF containing tetrodotoxin, Co2+ and Cs+, ISP was blocked by muscarine. No PMN displayed any M-type potassium current but only a current showing no voltage sensitivity over the range -100 to 0 mV, reversing near the expected EK +, hence consistent with a leak current. SP application to the spinal cord only (using a partitioned chamber) significantly increased the phrenic activity. Pretreatment with the NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid (AP5) decreased the C4 discharge duration and blocked the effect of SP, thus exhibiting an NMDA potentiation by SP. In conclusion, SP modulates postsynaptically the response of phrenic motoneurons to the inspiratory drive through the reduction of a leak conductance and the potentiation of the NMDA component of the synaptic input.

Augmented sodium currents contribute to the enhanced excitability of small diameter capsaicin-sensitive sensory neurons isolated from Nf1+/⁻ mice.

PubMed

Wang, Yue; Duan, J-H; Hingtgen, C M; Nicol, G D

2010-04-01

Neurofibromin, the product of the Nf1 gene, is a guanosine triphosphatase activating protein (GAP) for p21ras (Ras) that accelerates conversion of active Ras-GTP to inactive Ras-GDP. Sensory neurons with reduced levels of neurofibromin likely have augmented Ras-GTP activity. We reported previously that sensory neurons isolated from a mouse model with a heterozygous mutation of the Nf1 gene (Nf1+/⁻) exhibited greater excitability compared with wild-type mice. To determine the mechanism giving rise to the augmented excitability, differences in specific membrane currents were examined. Consistent with the enhanced excitability of Nf1+/⁻ neurons, peak current densities of both tetrodotoxin-resistant sodium current (TTX-R I(Na)) and TTX-sensitive (TTX-S) I(Na) were significantly larger in Nf1+/⁻ than in wild-type neurons. Although the voltages for half-maximal activation (V(0.5)) were not different, there was a significant depolarizing shift in the V(0.5) for steady-state inactivation of both TTX-R and TTX-S I(Na) in Nf1+/⁻ neurons. In addition, levels of persistent I(Na) were significantly larger in Nf1+/⁻ neurons. Neither delayed rectifier nor A-type potassium currents were altered in Nf1+/⁻ neurons. These results demonstrate that enhanced production of action potentials in Nf1+/⁻ neurons results, in part, from larger current densities and a depolarized voltage dependence of steady-state inactivation for I(Na) that potentially leads to a greater availability of sodium channels at voltages near the firing threshold for the action potential.

Experimental study of atmospheric-pressure micro-plasmas for the ambient sampling of conductive materials

NASA Astrophysics Data System (ADS)

Duan, Zhengchao; He, Feng; Si, Xinlu; Bradley, James W.; Ouyang, Jiting

2018-02-01

Conductive solid material sampling by micro-plasma under ambient atmosphere was studied experimentally. A high-voltage pulse generator was utilized to drive discharge between a tungsten needle and metal samples. The effects of pulse width on discharge, micro-plasma and sampling were investigated. The electrical results show that two discharge current pulses can be formed in one voltage pulse. The duration of the first current pulse is of the order of 100 ns. The duration of the second current pulse depends on the width of the voltage pulse. The electrical results also show that arc micro-plasma was generated during both current pulses. The results of the emission spectra of different sampled materials indicate that the relative emission intensity of elemental metal ions will increase with pulse width. The excitation temperature and electron density of the arc micro-plasmas increase with the voltage pulse width, which contributes to the increase of relative emission intensity of metal ions. The optical images and energy dispersive spectroscopy results of the sampling spots on metal surfaces indicate that discharge with a short voltage pulse can generate a small sputtering crater.

Depolarizing collisions with hydrogen: Neutral and singly ionized alkaline earths

DOE Office of Scientific and Technical Information (OSTI.GOV)

Manso Sainz, Rafael; Ramos, Andrés Asensio; Bueno, Javier Trujillo

2014-06-20

Depolarizing collisions are elastic or quasielastic collisions that equalize the populations and destroy the coherence between the magnetic sublevels of atomic levels. In astrophysical plasmas, the main depolarizing collider is neutral hydrogen. We consider depolarizing rates on the lowest levels of neutral and singly ionized alkali earths Mg I, Sr I, Ba I, Mg II, Ca II, and Ba II, due to collisions with H°. We compute ab initio potential curves of the atom-H° system and solve the quantum mechanical dynamics. From the scattering amplitudes, we calculate the depolarizing rates for Maxwellian distributions of colliders at temperatures T ≤ 10,000more » K. A comparative analysis of our results and previous calculations in the literature is completed. We discuss the effect of these rates on the formation of scattering polarization patterns of resonant lines of alkali earths in the solar atmosphere, and their effect on Hanle effect diagnostics of solar magnetic fields.« less

Pulse-Width-Modulating Driver for Brushless dc Motor

NASA Technical Reports Server (NTRS)

Salomon, Phil M.

1991-01-01

High-current pulse-width-modulating driver for brushless dc motor features optical coupling of timing signals from low-current control circuitry to high-current motor-driving circuitry. Provides high electrical isolation of motor-power supply, helping to prevent fast, high-current motor-driving pulses from being coupled through power supplies into control circuitry, where they interfere with low-current control signals.

Mechanism of blue-light-induced plasma-membrane depolarization in etiolated cucumber hypocotyls

NASA Technical Reports Server (NTRS)

Spalding, E. P.; Cosgrove, D. J.

1992-01-01

A large, transient depolarization of the plasma membrane precedes the rapid blue-light (BL)-induced growth suppression in etiolated seedlings of Cucumis sativus L. The mechanism of this voltage transient was investigated by applying inhibitors of ion channels and the plasma-membrane H(+)-ATPase, by manipulating extracellular ion concentrations, and by measuring cell input resistance and ATP levels. The depolarizing phase was not affected by Ca(2+)-channel blockers (verapamil, La3+) or by reducing extracellular free Ca2+ by treatment with ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA). However, these treatments did reduce the rate of repolarization, indicating an inward movement of Ca2+ is involved. No effects of the K(+)-channel blocker tetraethylammonium (TEA+) were detected. Vanadate and KCN, used to inhibit the H(+)-ATPase, reduced or completely inhibited the BL-induced depolarization. Levels of ATP increased by 11-26% after 1-2 min of BL. Input resistance of trichrome cells, measured with double-barreled microelectrodes, remained constant during the onset of the depolarization but decreased as the membrane voltage became more positive than -90 mV. The results indicate that the depolarization mechanism initially involves inactivation of the H(+)-ATPase with subsequent transient activation of one or more types of ion channels.

Gas metal arc welding fume generation using pulsed current

DOE Office of Scientific and Technical Information (OSTI.GOV)

Castner, H.R.

1994-12-31

This paper describes a study of the effects of pulsed welding current on the amount of welding fume and ozone produced during gas metal arc welding (GMAW) using a range of welding procedures and pulse parameters. The results reported in this paper show that pulsed current can reduce GMAW fumes compared to steady current. This research also shows that welding parameters need to be properly controlled if pulsed current is to be used to reduce welding fumes. Fume and ozone generation rates were measured during this study for GMAW of mild steel using copper-coated ER70S-3 electrode wire and 95%Ar-5%CO{sub 2}more » and 85%Ar-15%CO{sub 2} shielding gases. Welds were made with both steady current and pulsed current over a wide range of welding parameters. Fume generation rates for steady current were found to be typically between 0.2 g/min and 0.8 g/min which agrees with other researchers. No significant difference was found in the chemical composition of welding fumes from pulsed current compared to the composition of fumes generated by steady current. New technology that can reduce arc welding fumes is of significant interest to a wide range of companies that use arc welding processes and this research should assist these users in evaluating the potential for the application of this technology to their own operations.« less

Parkin elimination of mitochondria is important for maintenance of lens epithelial cell ROS levels and survival upon oxidative stress exposure.

PubMed

Brennan, Lisa; Khoury, Josef; Kantorow, Marc

2017-01-01

Age-related cataract is associated with oxidative stress and death of lens epithelial cells (LECs) whose survival is dependent on functional mitochondrial populations. Oxidative stress-induced depolarization/damage of LEC mitochondria results in increased reactive oxygen species (ROS) levels and cell death suggesting the need for a LEC mechanism to remove mitochondria depolarized/damaged upon oxidative stress exposure to prevent ROS release and LEC death. To date, a mechanism(s) for removal of depolarized/damaged LEC mitochondria has yet to be identified and the importance of eliminating oxidative stress-damaged mitochondria to prevent LEC ROS release and death has not been established. Here, we demonstrate that Parkin levels increase in LECs exposed to H 2 O 2 -oxidative stress. We establish that Parkin translocates to LEC mitochondria depolarized upon oxidative stress exposure and that Parkin recruits p62/SQSTM1 to depolarized LEC mitochondria. We demonstrate that translocation of Parkin results in the elimination of depolarized/damaged mitochondria and that Parkin clearance of LEC mitochondria is dependent on its ubiquitin ligase activity. Importantly, we demonstrate that Parkin elimination of damaged LEC mitochondria results in reduced ROS levels and increased survival upon oxidative stress exposure. These results establish that Parkin functions to eliminate LEC mitochondria depolarized/damaged upon oxidative stress exposure and that elimination of damaged mitochondria by Parkin is important for LEC homeostasis and survival. The data also suggest that mitochondrial quality control by Parkin could play a role in lens transparency. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Development of a Specific Impulse Balance for a Pulsed Capillary Discharge (Preprint)

DTIC Science & Technology

2008-06-13

thrust stand [rad/s] I. Introduction A capillary discharge based coaxial , electrothermal pulsed plasma thruster (PPT) is currently under...20-23 July 2008. 14. ABSTRACT A capillary discharge based pulsed plasma thruster is currently under development at the Air Force Research...Edwards AFB, CA 93524 A capillary discharge based pulsed plasma thruster is currently under development at the Air Force Research Laboratory. A

Effect of Pulse Rate on Loudness Discrimination in Cochlear Implant Users.

PubMed

Azadpour, Mahan; McKay, Colette M; Svirsky, Mario A

2018-03-12

Stimulation pulse rate affects current amplitude discrimination by cochlear implant (CI) users, indicated by the evidence that the JND (just noticeable difference) in current amplitude delivered by a CI electrode becomes larger at higher pulse rates. However, it is not clearly understood whether pulse rate would affect discrimination of speech intensities presented acoustically to CI processors, or what the size of this effect might be. Intensity discrimination depends on two factors: the growth of loudness with increasing sound intensity and the loudness JND (or the just noticeable loudness increment). This study evaluated the hypothesis that stimulation pulse rate affects loudness JND. This was done by measuring current amplitude JNDs in an experiment design based on signal detection theory according to which loudness discrimination is related to internal noise (which is manifested by variability in loudness percept in response to repetitions of the same physical stimulus). Current amplitude JNDs were measured for equally loud pulse trains of 500 and 3000 pps (pulses per second) by increasing the current amplitude of the target pulse train until it was perceived just louder than a same-rate or different-rate reference pulse train. The JND measures were obtained at two presentation levels. At the louder level, the current amplitude JNDs were affected by the rate of the reference pulse train in a way that was consistent with greater noise or variability in loudness perception for the higher pulse rate. The results suggest that increasing pulse rate from 500 to 3000 pps can increase loudness JND by 60 % at the upper portion of the dynamic range. This is equivalent to a 38 % reduction in the number of discriminable steps for acoustic and speech intensities.

Study of observed broad dielectric relaxation and compatibility of polysulfone - Polyvinylidenefluoride blends

NASA Astrophysics Data System (ADS)

Patel, Swarnim; Shrivas, Sandhya; Dubey, R. K.; Keller, J. M.

2018-05-01

Short circuit thermally stimulated depolarization current measurement techniques has been employed to investigate the dielectric relaxation behavior of PSF: PVDF blends. The samples taken were blends of composition PSF: PVDF:: 80:20; 85:15; 90:10 and 95:05 percent by weight. The thermograms were characterized by a high value of initial current, a low temperature peak around 75-80°C and a prominent broad peak in the temperature interval 130 to 160°C. The two polymers are found to form compatible blend in the studied composition range.

Current Pulses Momentarily Enhance Thermoelectric Cooling

NASA Technical Reports Server (NTRS)

Snyder, G. Jeffrey; Fleurial, Jean-Pierre; Caillat, Thierry; Chen, Gang; Yang, Rong Gui

2004-01-01

The rates of cooling afforded by thermoelectric (Peltier) devices can be increased for short times by applying pulses of electric current greater than the currents that yield maximum steady-state cooling. It has been proposed to utilize such momentary enhancements of cooling in applications in which diode lasers and other semiconductor devices are required to operate for times of the order of milliseconds at temperatures too low to be easily obtainable in the steady state. In a typical contemplated application, a semiconductor device would be in contact with the final (coldest) somewhat taller stage of a multistage thermoelectric cooler. Steady current would be applied to the stages to produce steady cooling. Pulsed current would then be applied, enhancing the cooling of the top stage momentarily. The principles of operation are straightforward: In a thermoelectric device, the cooling occurs only at a junction at one end of the thermoelectric legs, at a rate proportional to the applied current. However, Joule heating occurs throughout the device at a rate proportional to the current squared. Hence, in the steady state, the steady temperature difference that the device can sustain increases with current only to the point beyond which the Joule heating dominates. If a pulse of current greater than the optimum current (the current for maximum steady cooling) is applied, then the junction becomes momentarily cooled below its lowest steady temperature until thermal conduction brings the resulting pulse of Joule heat to the junction and thereby heats the junction above its lowest steady temperature. A theoretical and experimental study of such transient thermoelectric cooling followed by transient Joule heating in response to current pulses has been performed. The figure presents results from one of the experiments. The study established the essential parameters that characterize the pulse cooling effect, including the minimum temperature achieved, the maximum temperature overshoot, the time to reach minimum temperature, the time while cooled, and the time between pulses. It was found that at large pulse amplitude, the amount of pulse supercooling is about a fourth of the maximum steady-state temperature difference. For the particular thermoelectric device used in one set of the experiments, the practical optimum pulse amplitude was found to be about 3 times the optimum steady-state current. In a further experiment, a pulse cooler was integrated into a small commercial thermoelectric threestage cooler and found to provide several degrees of additional cooling for a time long enough to operate a semiconductor laser in a gas sensor.

Preferential expression and function of voltage-gated, O2-sensitive K+ channels in resistance pulmonary arteries explains regional heterogeneity in hypoxic pulmonary vasoconstriction: ionic diversity in smooth muscle cells.

PubMed

Archer, Stephen L; Wu, Xi-Chen; Thébaud, Bernard; Nsair, Ali; Bonnet, Sebastien; Tyrrell, Ben; McMurtry, M Sean; Hashimoto, Kyoko; Harry, Gwyneth; Michelakis, Evangelos D

2004-08-06

Hypoxic pulmonary vasoconstriction (HPV) is initiated by inhibition of O2-sensitive, voltage-gated (Kv) channels in pulmonary arterial smooth muscle cells (PASMCs). Kv inhibition depolarizes membrane potential (E(M)), thereby activating Ca2+ influx via voltage-gated Ca2+ channels. HPV is weak in extrapulmonary, conduit pulmonary arteries (PA) and strong in precapillary resistance arteries. We hypothesized that regional heterogeneity in HPV reflects a longitudinal gradient in the function/expression of PASMC O2-sensitive Kv channels. In adult male Sprague Dawley rats, constrictions to hypoxia, the Kv blocker 4-aminopyridine (4-AP), and correolide, a Kv1.x channel inhibitor, were endothelium-independent and greater in resistance versus conduit PAs. Moreover, HPV was dependent on Kv-inhibition, being completely inhibited by pretreatment with 4-AP. Kv1.2, 1.5, Kv2.1, Kv3.1b, Kv4.3, and Kv9.3. mRNA increased as arterial caliber decreased; however, only Kv1.5 protein expression was greater in resistance PAs. Resistance PASMCs had greater K+ current (I(K)) and a more hyperpolarized E(M) and were uniquely O2- and correolide-sensitive. The O2-sensitive current (active at -65 mV) was resistant to iberiotoxin, with minimal tityustoxin sensitivity. In resistance PASMCs, 4-AP and hypoxia inhibited I(K) 57% and 49%, respectively, versus 34% for correolide. Intracellular administration of anti-Kv1.5 antibodies inhibited correolide's effects. The hypoxia-sensitive, correolide-insensitive I(K) (15%) was conducted by Kv2.1. Anti-Kv1.5 and anti-Kv2.1 caused additive depolarization in resistance PASMCs (Kv1.5>Kv2.1) and inhibited hypoxic depolarization. Heterologously expressed human PASMC Kv1.5 generated an O2- and correolide-sensitive I(K) like that in resistance PASMCs. In conclusion, Kv1.5 and Kv2.1 account for virtually all the O2-sensitive current. HPV occurs in a Kv-enriched resistance zone because resistance PASMCs preferentially express O2-sensitive Kv-channels.

The IK1/Kir2.1 channel agonist zacopride prevents and cures acute ischemic arrhythmias in the rat

PubMed Central

Zhai, Xu-Wen; Zhang, Li; Guo, Yun-Fei; Yang, Ying; Wang, Dong-Ming; Zhang, Yan; Li, Pan; Niu, Yi-Fan; Feng, Qi-Long; Wu, Bo-Wei; Cao, Ji-Min; Liu, Qing-Hua

2017-01-01

Arrhythmogenesis in acute myocardial infarction (MI) is associated with depolarization of resting membraine potential (RMP) and decrease of inward rectifier potassium current (IK1) in cardiomyocytes. However, clinical anti-arrhythmic agents that primarily act on RMP by enhancing the IK1 channel are not currently available. We hypothesized that zacopride, a selective and moderate agonist of the IK1/Kir2.1 channels, prevents and cures acute ischemic arrhythmias. To test this viewpoint, adult Sprague-Dawley (SD) rats were subjected to MI by ligating the left main coronary artery. The antiarrhythmic effects of zacopride (i.v. infusion) were observed in the settings of pre-treatment (zacopride given 3 min prior to coronary occlusion), post-treatment (zacopride given 3 min after coronary occlusion) and therapeutic treatment (zacopride given 30 s after the onset of the first sustained ventricular tachycardia (VT)/ventricular fibrillation (VF) post MI). In all the three treatment modes, zacopride (15 μg/kg) inhibited MI-induced ventricular tachyarrhythmias, as shown by significant decreases in the premature ventricular contraction (PVC) and the duration and incidence of VT or VF. In Langendorff perfused rat hearts, the antiarrhythmic effect of 1 μmol/L zacopride were reversed by 1 μmol/L BaCl2, a blocker of IK1 channel. Patch clamp results in freshly isolated rat ventricular myocytes indicated that zacopride activated the IK1 channel and thereby reversed hypoxia-induced RMP depolarization and action potential duration (APD) prolongation. In addition, zacopride (1 μmol/L) suppressed hypoxia- or isoproterenol- induced delayed afterdepolarizations (DADs). In Kir2.x transfected Chinese hamster ovary (CHO) cells, zacopride activated the Kir2.1 homomeric channel but not the Kir2.2 or Kir2.3 channels. These results support our hypothesis that moderately enhancing IK1/Kir2.1 currents as by zacopride rescues ischemia- and hypoxia- induced RMP depolarization, and thereby prevents and cures acute ischemic arrhythmias. This study brings a new viewpoint to antiarrhythmic theories and provides a promising target for the treatment of acute ischemic arrhythmias. PMID:28542320

Evidence of negative leaders which precede fast rise ICC pulses of upward

NASA Astrophysics Data System (ADS)

Yoshida, S.; Akita, M.; Morimoto, T.; Ushio, T.; Kawasaki, Z.; Wang, D.; Takagi, N.

2008-12-01

During winter thunderstorm season in Japan, a lightning observation campaign was conducted with using a VHF broadband digital interferometer (DITF), a capacitive antenna, and Rogowski coils to study the charge transfer mechanism associated with ICC pulses of upward lightning. All the detection systems recorded one upward negative lightning stroke hitting a lightning protection tower. The upward lightning consists of only the Initial Stage (IS) with one upward positive leader and six ICC pulses. The six ICC pulses are sub-classified clearly into two types according to current pulse shapes. The type 1 ICC pulses have a higher geometric mean (GM) current peak of 17 kA and a shorter GM 10-90% risetime of 8.9 μs, while the type 2 ICC pulses have a lower GM current peak of 0.34 kA and longer GM 10-90% risetime of 55 μs. The type 1 ICC pulses have the preceding negative leaders connecting to the channel of the continuing current, while the type 2 ICC pulses have no clear preceding negative leader. These negative leaders prior to the type 1 ICC pulses probably caused the current increases of the ICC pulses, which means that the negative leaders created the channels for the ICC pulses. The height of the space charge transferred by one of the type 1 ICC pulses was estimated about 700 m above sea level at most. This observation result is the first evidence to show explicitly the existence of the negative leaders prior to the fast rise ICC pulse. Furthermore, the result shows that space charge could exist at a low attitude such as 700 m above sea level. This fact is one of the reasons why upward lightning occurs even from rather low structures during winter thunderstorm season in Japan.

Progress of long pulse operation with high performance plasma in KSTAR

NASA Astrophysics Data System (ADS)

Bae, Young; Kstar Team

2015-11-01

Recent KSTAR experiments showed the sustained H-mode operation up to the pulse duration of 46 s at the plasma current of 600 kA. The long-pulse H-mode operation has been supported by long-pulse capable neutral beam injection (NBI) system with high NB current drive efficiency attributed by highly tangential injections of three beam sources. In next phase, aiming to demonstrate the long pulse stationary high performance plasma operation, we are attempting the long pulse inductive operation at the higher performance (MA plasma current, high normalized beta, and low q95) for the final goal of demonstration of ITER-like baseline scenario in KSTAR with progressive improvement of the plasma shape control and higher neutral beam injection power. This paper presents the progress of long pulse operation and the analysis of energy confinement time and non-inductive current drive in KSTAR.

LINEAR COUNT-RATE METER

DOEpatents

Henry, J.J.

1961-09-01

A linear count-rate meter is designed to provide a highly linear output while receiving counting rates from one cycle per second to 100,000 cycles per second. Input pulses enter a linear discriminator and then are fed to a trigger circuit which produces positive pulses of uniform width and amplitude. The trigger circuit is connected to a one-shot multivibrator. The multivibrator output pulses have a selected width. Feedback means are provided for preventing transistor saturation in the multivibrator which improves the rise and decay times of the output pulses. The multivibrator is connected to a diode-switched, constant current metering circuit. A selected constant current is switched to an averaging circuit for each pulse received, and for a time determined by the received pulse width. The average output meter current is proportional to the product of the counting rate, the constant current, and the multivibrator output pulse width.

Nonlinear effects of hyperpolarizing shifts in activation of mutant Nav1.7 channels on resting membrane potential

PubMed Central

Estacion, Mark

2017-01-01

The Nav1.7 sodium channel is preferentially expressed within dorsal root ganglion (DRG) and sympathetic ganglion neurons. Gain-of-function mutations that cause the painful disorder inherited erythromelalgia (IEM) shift channel activation in a hyperpolarizing direction. When expressed within DRG neurons, these mutations produce a depolarization of resting membrane potential (RMP). The biophysical basis for the depolarized RMP has to date not been established. To explore the effect on RMP of the shift in activation associated with a prototypical IEM mutation (L858H), we used dynamic-clamp models that represent graded shifts that fractionate the effect of the mutation on activation voltage dependence. Dynamic-clamp recording from DRG neurons using a before-and-after protocol for each cell made it possible, even in the presence of cell-to-cell variation in starting RMP, to assess the effects of these graded mutant models. Our results demonstrate a nonlinear, progressively larger effect on RMP as the shift in activation voltage dependence becomes more hyperpolarized. The observed differences in RMP were predicted by the “late” current of each mutant model. Since the depolarization of RMP imposed by IEM mutant channels is known, in itself, to produce hyperexcitability of DRG neurons, the development of pharmacological agents that normalize or partially normalize activation voltage dependence of IEM mutant channels merits further study. NEW & NOTEWORTHY Inherited erythromelalgia (IEM), the first human pain disorder linked to a sodium channel, is widely regarded as a genetic model of neuropathic pain. IEM is produced by Nav1.7 mutations that hyperpolarize activation. These mutations produce a depolarization of resting membrane potential (RMP) in dorsal root ganglion neurons. Using dynamic clamp to explore the effect on RMP of the shift in activation, we demonstrate a nonlinear effect on RMP as the shift in activation voltage dependence becomes more hyperpolarized. PMID:28148645

Voltage-gated sodium channels in taste bud cells.

PubMed

Gao, Na; Lu, Min; Echeverri, Fernando; Laita, Bianca; Kalabat, Dalia; Williams, Mark E; Hevezi, Peter; Zlotnik, Albert; Moyer, Bryan D

2009-03-12

Taste bud cells transmit information regarding the contents of food from taste receptors embedded in apical microvilli to gustatory nerve fibers innervating basolateral membranes. In particular, taste cells depolarize, activate voltage-gated sodium channels, and fire action potentials in response to tastants. Initial cell depolarization is attributable to sodium influx through TRPM5 in sweet, bitter, and umami cells and an undetermined cation influx through an ion channel in sour cells expressing PKD2L1, a candidate sour taste receptor. The molecular identity of the voltage-gated sodium channels that sense depolarizing signals and subsequently initiate action potentials coding taste information to gustatory nerve fibers is unknown. We describe the molecular and histological expression profiles of cation channels involved in electrical signal transmission from apical to basolateral membrane domains. TRPM5 was positioned immediately beneath tight junctions to receive calcium signals originating from sweet, bitter, and umami receptor activation, while PKD2L1 was positioned at the taste pore. Using mouse taste bud and lingual epithelial cells collected by laser capture microdissection, SCN2A, SCN3A, and SCN9A voltage-gated sodium channel transcripts were expressed in taste tissue. SCN2A, SCN3A, and SCN9A were expressed beneath tight junctions in subsets of taste cells. SCN3A and SCN9A were expressed in TRPM5 cells, while SCN2A was expressed in TRPM5 and PKD2L1 cells. HCN4, a gene previously implicated in sour taste, was expressed in PKD2L1 cells and localized to cell processes beneath the taste pore. SCN2A, SCN3A and SCN9A voltage-gated sodium channels are positioned to sense initial depolarizing signals stemming from taste receptor activation and initiate taste cell action potentials. SCN2A, SCN3A and SCN9A gene products likely account for the tetrodotoxin-sensitive sodium currents in taste receptor cells.

Real-Time Optical Diagnosis of the Rat Brain Exposed to a Laser-Induced Shock Wave: Observation of Spreading Depolarization, Vasoconstriction and Hypoxemia-Oligemia

PubMed Central

Sato, Shunichi; Kawauchi, Satoko; Okuda, Wataru; Nishidate, Izumi; Nawashiro, Hiroshi; Tsumatori, Gentaro

2014-01-01

Despite many efforts, the pathophysiology and mechanism of blast-induced traumatic brain injury (bTBI) have not yet been elucidated, partially due to the difficulty of real-time diagnosis and extremely complex factors determining the outcome. In this study, we topically applied a laser-induced shock wave (LISW) to the rat brain through the skull, for which real-time measurements of optical diffuse reflectance and electroencephalogram (EEG) were performed. Even under conditions showing no clear changes in systemic physiological parameters, the brain showed a drastic light scattering change accompanied by EEG suppression, which indicated the occurrence of spreading depression, long-lasting hypoxemia and signal change indicating mitochondrial energy impairment. Under the standard LISW conditions examined, hemorrhage and contusion were not apparent in the cortex. To investigate events associated with spreading depression, measurement of direct current (DC) potential, light scattering imaging and stereomicroscopic observation of blood vessels were also conducted for the brain. After LISW application, we observed a distinct negative shift in the DC potential, which temporally coincided with the transit of a light scattering wave, showing the occurrence of spreading depolarization and concomitant change in light scattering. Blood vessels in the brain surface initially showed vasodilatation for 3–4 min, which was followed by long-lasting vasoconstriction, corresponding to hypoxemia. Computer simulation based on the inverse Monte Carlo method showed that hemoglobin oxygen saturation declined to as low as ∼35% in the long-term hypoxemic phase. Overall, we found that topical application of a shock wave to the brain caused spreading depolarization/depression and prolonged severe hypoxemia-oligemia, which might lead to pathological conditions in the brain. Although further study is needed, our findings suggest that spreading depolarization/depression is one of the key events determining the outcome in bTBI. Furthermore, a rat exposed to an LISW(s) can be a reliable laboratory animal model for blast injury research. PMID:24416150

Fast and efficient STT switching in MTJ using additional transient pulse current

NASA Astrophysics Data System (ADS)

Pathak, Sachin; Cha, Jongin; Jo, Kangwook; Yoon, Hongil; Hong, Jongill

2017-06-01

We propose a profile of write pulse current-density to switch magnetization in a perpendicular magnetic tunnel junction to reduce switching time and write energy as well. Our simulated results show that an overshoot transient pulse current-density (current spike) imposed to conventional rectangular-shaped pulse current-density (main pulse) significantly improves switching speed that yields the reduction in write energy accordingly. For example, we could dramatically reduce the switching time by 80% and thereby reduce the write energy over 9% in comparison to the switching without current spike. The current spike affects the spin dynamics of the free layer and reduces the switching time mainly due to spin torque induced. On the other hand, the large Oersted field induced causes changes in spin texture. We believe our proposed write scheme can make a breakthrough in magnetic random access memory technology seeking both high speed operation and low energy consumption.

Optogenetic Stimulation of Arcuate Nucleus Kiss1 Neurons Reveals a Steroid-Dependent Glutamatergic Input to POMC and AgRP Neurons in Male Mice

PubMed Central

Nestor, Casey C; Qiu, Jian; Padilla, Stephanie L.; Zhang, Chunguang; Bosch, Martha A.; Fan, Wei; Aicher, Sue A.; Palmiter, Richard D.

2016-01-01

Kisspeptin (Kiss1) neurons are essential for reproduction, but their role in the control of energy balance and other homeostatic functions remains unclear. Proopiomelanocortin (POMC) and agouti-related peptide (AgRP) neurons, located in the arcuate nucleus (ARC) of the hypothalamus, integrate numerous excitatory and inhibitory inputs to ultimately regulate energy homeostasis. Given that POMC and AgRP neurons are contacted by Kiss1 neurons in the ARC (Kiss1ARC) and they express androgen receptors, Kiss1ARC neurons may mediate the orexigenic action of testosterone via POMC and/or AgRP neurons. Quantitative PCR analysis of pooled Kiss1ARC neurons revealed that mRNA levels for Kiss1 and vesicular glutamate transporter 2 were higher in castrated male mice compared with gonad-intact males. Single-cell RT-PCR analysis of yellow fluorescent protein (YFP) ARC neurons harvested from males injected with AAV1-EF1α-DIO-ChR2:YFP revealed that 100% and 88% expressed mRNAs for Kiss1 and vesicular glutamate transporter 2, respectively. Whole-cell, voltage-clamp recordings from nonfluorescent postsynaptic ARC neurons showed that low frequency photo-stimulation (0.5 Hz) of Kiss1-ChR2:YFP neurons elicited a fast glutamatergic inward current in POMC and AgRP neurons. Paired-pulse, photo-stimulation revealed paired-pulse depression, which is indicative of greater glutamate release, in the castrated male mice compared with gonad-intact male mice. Group I and group II metabotropic glutamate receptor agonists depolarized and hyperpolarized POMC and AgRP neurons, respectively, which was mimicked by high frequency photo-stimulation (20 Hz) of Kiss1ARC neurons. Therefore, POMC and AgRP neurons receive direct steroid- and frequency-dependent glutamatergic synaptic input from Kiss1ARC neurons in male mice, which may be a critical pathway for Kiss1 neurons to help coordinate energy homeostasis and reproduction. PMID:27093227

a 33GHZ and 95GHZ Cloud Profiling Radar System (cprs): Preliminary Estimates of Particle Size in Precipitation and Clouds.

NASA Astrophysics Data System (ADS)

Sekelsky, Stephen Michael

1995-11-01

The Microwave Remote Sensing Laboratory (MIRSL) st the University of Massachusetts has developed a unique single antenna, dual-frequency polarimetric Cloud Profiling Radar System (CPRS). This project was funded by the Department of Energy's Atmospheric Radiation Measurement (ARM) program, and was intended to help fill the void of ground-based remote sensors capable of characterizing cloud microphysical properties. CPRS is unique in that it can simultaneously measure the complex power backscattered from clouds at 33 GHz and 95 GHz through the same aperture. Both the 33 GHz and 95 GHz channels can transmit pulse-to-pulse selectable vertical or horizontal polarization, and simultaneously record both the copolarized and crosspolarized backscatter. CPRS Doppler, polarimetric and dual-wavelength reflectivity measurements combined with in situ cloud measurements should lead to the development of empirical models that can more accurately classify cloud-particle phase and habit, and make better quantitative estimates of particle size distribution parameters. This dissertation describes the CPRS hardware, and presents colocated 33 GHz and 95 GHz measurements that illustrate the use of dual-frequency measurements to estimate particle size when Mie scattering, is observed in backscatter from rain and ice-phase clouds. Polarimetric measurements are presented as a means of discriminating cloud phase (ice-water) and estimating crystal shape in cirrus clouds. Polarimetric and dual-wavelength observations of insects are also presented with a brief discussion of their impact on the interpretation of precipitation and liquid cloud measurements. In precipitation, Diermendjian's equations for Mie backscatter (1) and the Marshal-Palmer drop-size distribution are used to develop models relating differences in the reflectivity and mean velocity at 33 GHz and 95 GHz to the microphysical parameters of rain. These models are then used to estimate mean droplet size from CPRS measurements of drizzle, which were collected in July, 1993 during the system's first field test in Lincoln, NE. The dissertation also presents cirrus cloud and other measurements collected during the DOE-sponsored Remote Cloud Sensing Intensive Operations Period (RCS-IOP) experiment in April, 1994. Zenith-pointing cirrus measurements show small differences in 33 GHz and 95 GHz reflectivity, as models have predicted (2). Depolarization was also detected in a few cases when ice crystals precipitated from the base of a cloud. On May 29, 1994 CPRS observed a convective storm that produced a cirrus anvil cloud and hail. These storms are one 'engine' producing cirrus clouds and are currently a topic of intensive research by climatologists. Both zenith-pointing and range-height data formats are presented. Measurements of depolarization above the melting/layer are compared to in situ observations of particle size and shape. The RCS-IOP experiment also provided a first opportunity to verify our calibration with aircraft in situ measurements, and to compare our cloud measurements to those collected by other remote sensors. (Abstract shortened by UMI.).

Inhibitory effect of aniracetam on N-type calcium current in acutely isolated rat neuronal cells.

PubMed

Koike, H; Saito, H; Matsuki, N

1993-04-01

Effects of aniracetam on whole-cell calcium currents were studied in acutely isolated neuronal cells from postnatal rat ventromedial hypothalamus. There were three types of inward calcium currents, one low-threshold transient current and two high-threshold sustained currents. The nicardipine sensitive L-type current was activated at -20 mV or more depolarized potentials, and the omega-conotoxin sensitive N-type current was recorded at more positive potentials than the L-type. Aniracetam inhibited the N-type current in a dose-dependent manner without affecting the other two types of calcium currents. The effect appeared soon after the addition and lasted for several minutes during washing. Since the N-type current is thought to regulate the release of transmitters, the inhibitory effect may contribute to the nootropic property of aniracetam by modifying the neurotransmission.

PIC simulation of the vacuum power flow for a 5 terawatt, 5 MV, 1 MA pulsed power system

NASA Astrophysics Data System (ADS)

Liu, Laqun; Zou, Wenkang; Liu, Dagang; Guo, Fan; Wang, Huihui; Chen, Lin

2018-03-01

In this paper, a 5 Terawatt, 5 MV, 1 MA pulsed power system based on vacuum magnetic insulation is simulated by the particle-in-cell (PIC) simulation method. The system consists of 50 100-kV linear transformer drive (LTD) cavities in series, using magnetically insulated induction voltage adder (MIVA) technology for pulsed power addition and transmission. The pulsed power formation and the vacuum power flow are simulated when the system works in self-limited flow and load-limited flow. When the pulsed power system isn't connected to the load, the downstream magnetically insulated transmission line (MITL) works in the self-limited flow, the maximum of output current is 1.14 MA and the amplitude of voltage is 4.63 MV. The ratio of the electron current to the total current is 67.5%, when the output current reached the peak value. When the impedance of the load is 3.0 Ω, the downstream MITL works in the self-limited flow, the maximums of output current and the amplitude of voltage are 1.28 MA and 3.96 MV, and the ratio of the electron current to the total current is 11.7% when the output current reached the peak value. In addition, when the switches are triggered in synchronism with the passage of the pulse power flow, it effectively reduces the rise time of the pulse current.

An Architecture Providing Depolarization Ratio Capability for a Multi-Wavelength Raman Lidar: Implementation and First Measurements

PubMed Central

Sicard, Michaël; Granados-Muñoz, María-José; Ben Chahed, Enis; Muñoz-Porcar, Constantino; Barragán, Rubén; Rocadenbosch, Francesc; Vidal, Eric

2017-01-01

A new architecture for the measurement of depolarization produced by atmospheric aerosols with a Raman lidar is presented. The system uses two different telescopes: one for depolarization measurements and another for total-power measurements. The system architecture and principle of operation are described. The first experimental results are also presented, corresponding to a collection of atmospheric conditions over the city of Barcelona. PMID:29261170

Hypothermia for Patients Requiring Evacuation of Subdural Hematoma: Effect on Spreading Depolarizations

DTIC Science & Technology

2017-10-01

AWARD NUMBER: W81XWH-16-C-0161 TITLE: Hypothermia for Patients Requiring Evacuation of Subdural Hematoma: Effect on Spreading Depolarizations...4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-16-C-0161 Hypothermia for Patients Requiring Evacuation of Subdural Hematoma: Effect on Spreading...in a sub-study of the HOPES trial to assess the effects of hypothermia on the pathologic mechanism of spreading depolarizations (SD). HOPES is a

Additive for iron disulfide cathodes used in thermal batteries

DOEpatents

Armijo, James R.; Searcy, Jimmie Q.

1983-01-01

The invention comprises thermal batteries employing an FeS.sub.2 depolarizer, i.e. cathode material, and the depolarizer itself. A minor amount of CaSi.sub.2 preferably, 1-3% by weight is provided as an additive in the FeS.sub.2 depolarizer to eliminate the voltage transient (spike) which normally occurs upon activation of batteries of this type. The amount of FeS.sub.2 by weight generally comprises 64-90%.

A review of depolarization modeling for earth-space radio paths at frequencies above 10 GHz

NASA Technical Reports Server (NTRS)

Bostian, C. W.; Stutzman, W. L.; Gaines, J. M.

1982-01-01

A review is presented of models for the depolarization, caused by scattering from raindrops and ice crystals, that limits the performance of dual-polarized satellite communication systems at frequencies above 10 GHz. The physical mechanisms of depolarization as well as theoretical formulations and empirical data are examined. Three theoretical models, the transmission, attenuation-derived, and scaling models, are described and their relative merits are considered.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guo, Xiaotong; Mao, Jirong; Wang, Jiancheng, E-mail: jirongmao@mail.ynao.ac.cn

We carefully examine the depolarization feature of blazars in the optical and near-infrared bands using the sample of Mead et al. Magnetohydrodynamics turbulence could be one possible reason for the depolarization of optical/infrared blazars when we apply the theoretical analysis of Lazarian and Pogosyan. We further identify in the sample that the depolarization results shown in most blazars roughly obey the form of the three-dimensional anisotropic Kolmogorov scaling. The effective Faraday rotation window length scale is not small enough to resolve the polarization correlation length scale in the blazar sample. The depolarization and the related turbulent features show diversities inmore » different blazar sources. We suggest more simultaneous observations in both the optical/infrared and the high-energy bands for the study of the blazar polarization.« less

The anomalous depolarization anisotropy in the central backscattering area for turbid medium with Mie scatterers

NASA Astrophysics Data System (ADS)

Wang, Xuezhen; Lai, Jiancheng; Song, Yang; Li, Zhenhua

2018-05-01

It is generally recognized that circularly polarized light is preferentially maintained over linearly polarized light in turbid medium with Mie scatterers. However, in this work, the anomalous depolarization anisotropy is reported in the backscattering area near the point of illumination. Both experimental and Monte Carlo simulations show preferential retention of linear polarization states compared to circular polarization states in a specific backscattering area. Further analysis indicates that the anomalous depolarization behavior in the specific area is induced by lateral scattering events, which own low circular polarization memory. In addition, it is also found that the size of the anomalous depolarization area is related to the transport mean free path of the turbid medium.

Forward voltage short-pulse technique for measuring high power laser array junction temperature

NASA Technical Reports Server (NTRS)

Meadows, Byron L. (Inventor); Amzajerdian, Frazin (Inventor); Barnes, Bruce W. (Inventor); Baker, Nathaniel R. (Inventor)

2012-01-01

The present invention relates to a method of measuring the temperature of the P-N junction within the light-emitting region of a quasi-continuous-wave or pulsed semiconductor laser diode device. A series of relatively short and low current monitor pulses are applied to the laser diode in the period between the main drive current pulses necessary to cause the semiconductor to lase. At the sufficiently low current level of the monitor pulses, the laser diode device does not lase and behaves similar to an electronic diode. The voltage across the laser diode resulting from each of these low current monitor pulses is measured with a high degree of precision. The junction temperature is then determined from the measured junction voltage using their known linear relationship.

Pulse-dose radiofrequency treatment in pain management-initial experience.

PubMed

Ojango, Christine; Raguso, Mario; Fiori, Roberto; Masala, Salvatore

2018-05-01

Radiofrequency procedures have been used for treating various chronic pain conditions for decades. These minimally invasive percutaneous treatments employ an alternating electrical current with oscillating radiofrequency wavelengths to eliminate or alter pain signals from the targeted site. The aim of the continuous radiofrequency procedure is to increase the temperature sufficiently to create an irreversible thermal lesion on nerve fibres and thus permanently interrupt pain signals. The pulsed radiofrequency procedure utilises short pulses of radiofrequency current with intervals of longer pauses to avert a temperature increase to the level of permanent tissue damage. The goal of these pulses is to alter the processing of pain signals, but to avoid relevant structural damage to nerve fibres, as seen in the continuous radiofrequency procedure. The pulse-dose radiofrequency procedure is a technical improvement of the pulsed radiofrequency technique in which the delivery mode of the current is adapted. During the pulse-dose radiofrequency procedure thermal damage is avoided. In addition, the amplitude and width of the consecutive pulses are kept the same. The method ensures that each delivered pulse keeps the same characteristics and therefore the dose is similar between patients. The current review outlines the pulse-dose radiofrequency procedure and presents our institution's chronic pain management studies.

Pulse generator using transistors and silicon controlled rectifiers produces high current pulses with fast rise and fall times

NASA Technical Reports Server (NTRS)

Woolfson, M. G.

1966-01-01

Electrical pulse generator uses power transistors and silicon controlled rectifiers for producing a high current pulse having fast rise and fall times. At quiescent conditions, the standby power consumption of the circuit is equal to zero.

Oscillatory dependence of current driven domain wall motion on current pulse length

NASA Astrophysics Data System (ADS)

Thomas, Luc

2007-03-01

The motion of domain walls (DW) in magnetic nanowires driven by spin torque from spin-polarized current is of considerable interest. Most previous work has considered the effect of dc or ˜microsecond long current pulses. Here, we show that the dynamics of DWs driven by nanosecond-long current pulses is unexpectedly complex. In particular, we show that the current driven motion of a DW, confined to a pinning site in a permalloy nanowire, exhibits an oscillatory dependence on the current pulse length with a period of just a few nanoseconds [1]. This behavior can be understood within a surprisingly straightforward one dimensional analytical model of the DW's motion. When a current pulse is applied, the DW's position oscillates within the pinning potential out of phase with the DW's out-of-plane magnetization, where the latter acts like the DW's momentum. Thus, the current driven motion of the DW is akin to a harmonic oscillator, whose frequency is determined by the ``mass'' of the DW and where the restoring force is related to the slope of the pinning potential. Remarkably, when the current pulse is turned off during phases of the DW motion when it has enough momentum, the amplitude of the oscillations can be amplified such that the DW exits the pinning potential well after the pulse is turned off. This oscillatory depinning occurs for currents smaller than the dc threshold current, and, moreover, the DW moves against the electron flow, opposite to the propagation direction above the dc threshold. These effects can be further amplified by using trains of current pulses whose lengths and separations are matched to the DW's oscillation period. In this way, we have demonstrated a five fold reduction in the threshold current required to move a DW out of a pinning site, making this effect potentially important for technological applications. [1] L. Thomas, M. Hayashi, X. Jiang, R. Moriya, C. Rettner and S.S.P. Parkin, Nature 443, 197 (2006).

The detailed characteristics of positive corona current pulses in the line-to-plane electrodes

NASA Astrophysics Data System (ADS)

Xuebao, LI; Dayong, LI; Qian, ZHANG; Yinfei, LI; Xiang, CUI; Tiebing, LU

2018-05-01

The corona current pulses generated by corona discharge are the sources of the radio interference from transmission lines and the detailed characteristics of the corona current pulses from conductor should be investigated in order to reveal their generation mechanism. In this paper, the line-to-plane electrodes are designed to measure and analyze the characteristics of corona current pulses from positive corona discharges. The influences of inter-electrode gap and line diameters on the detail characteristics of corona current pulses, such as pulse amplitude, rise time, duration time and repetition frequency, are carefully analyzed. The obtained results show that the pulse amplitude and the repetition frequency increase with the diameter of line electrode when the electric fields on the surface of line electrodes are same. With the increase of inter-electrode gap, the pulse amplitude and the repetition frequency first decrease and then turn to be stable, while the rise time first increases and finally turns to be stable. The distributions of electric field and space charges under the line electrodes are calculated, and the influences of inter-electrode gap and line electrode diameter on the experimental results are qualitatively explained.

CaMKII-dependent endoplasmic reticulum fission by whisker stimulation and during cortical spreading depolarization.

PubMed

Kucharz, Krzysztof; Lauritzen, Martin

2018-04-01

Cortical spreading depolarization waves, the cause underlying migraine aura, are also the markers and mechanism of pathology in the acutely injured human brain. Propagation of spreading depolarization wave uniquely depends on the interaction between presynaptic and postsynaptic glutamate N-methyl-d-aspartate receptors (NMDARs). In the normally perfused brain, even a single wave causes a massive depolarization of neurons and glia, which results in transient loss of neuronal function and depression of the ongoing electrocorticographic activity. Endoplasmic reticulum is the cellular organelle of particular importance for modulation of neurotransmission. Neuronal endoplasmic reticulum structure is assumed to be persistently continuous in neurons, but is rapidly lost within 1 to 2 min of global cerebral ischaemia, i.e. the organelle disintegrates by fission. This phenomenon appears to be timed with the cardiac arrest-induced cortical spreading depolarizations, rather than ensuing cell death. To what extent NMDAR-dependent processes may trigger neuronal endoplasmic reticulum fission and whether fission is reversible in the normally perfused brain is unknown. We used two-photon microscopy to examine neuronal endoplasmic reticulum structural dynamics during whisker stimulation and cortical spreading depolarizations in vivo. Somatosensory stimulation triggered loss of endoplasmic reticulum continuity, a likely outcome of constriction and fission, in dendritic spines within less than 10 s of stimulation, which was spontaneously reversible and recovery to normal took 5 min. The endoplasmic reticulum fission was inhibited by blockade of NMDAR and Ca2+/calmodulin-dependent protein kinase II (CaMKII) activated downstream of the NMDARs, whereas inhibition of guanosine triphosphate hydrolases hindered regain of endoplasmic reticulum continuity, i.e. fusion. In contrast to somatosensory stimulation, endoplasmic reticulum fission during spreading depolarization was widespread and present in dendrites and spines, and was preceded by dramatic rise in intracellular Ca2+. The endoplasmic reticulum fission during spreading depolarization was more persistent, as 1 h after the depolarization cortical neurons still exhibited loss of endoplasmic reticulum continuity. Notably, endoplasmic reticulum fission was accompanied with loss of electrocorticographic activity, whereas subsequent regain of synaptic function paralleled the organelle fusion. Furthermore, blocking CaMKII activity partly rescued endoplasmic reticulum fission and markedly shortened the recovery time of brain spontaneous activity. Thus, prevention of endoplasmic reticulum fission with CaMKII inhibitors may be a novel strategy to rescue brain function in patients with migraine and a promising therapeutic avenue in the acutely injured brain.

Effect of a superconducting coil as a fault current limiter on current density distribution in BSCCO tape after an over-current pulse

NASA Astrophysics Data System (ADS)

Tallouli, M.; Shyshkin, O.; Yamaguchi, S.

2017-07-01

The development of power transmission lines based on long-length high temperature superconducting (HTS) tapes is complicated and technically challenging task. A serious problem for transmission line operation could become HTS power cable damage due to over-current pulse conditions. To avoid the cable damage in any urgent case the superconducting coil technology, i.e. superconductor fault current limiter (SFCL) is required. Comprehensive understanding of the current density characteristics of HTS tapes in both cases, either after pure over-current pulse or after over-current pulse limited by SFCL, is needed to restart or to continue the operation of the power transmission line. Moreover, current density distribution along and across the HTS tape provides us with the sufficient information about the quality of the tape performance in different current feeding regimes. In present paper we examine BSCCO HTS tape under two current feeding regimes. The first one is 100A feeding preceded by 900A over-current pulse. In this case none of tape protection was used. The second scenario is similar to the fist one but SFCL is used to limit an over-current value. For both scenarios after the pulse is gone and the current feeding is set up at 100A we scan magnetic field above the tape by means of Hall probe sensor. Then the feeding is turned of and the magnetic field scanning is repeated. Using the inverse problem numerical solver we calculate the corresponding direct and permanent current density distributions during the feeding and after switch off. It is demonstrated that in the absence of SFCL the current distribution is highly peaked at the tape center. At the same time the current distribution in the experiment with SFCL is similar to that observed under normal current feeding condition. The current peaking in the first case is explained by the effect of an opposite electric field induced at the tape edges during the overcurrent pulse decay, and by degradation of superconductivity at the edges due to penetration of magnetic field in superconducting core during the pulse.

Active lamp pulse driver circuit. [optical pumping of laser media

NASA Technical Reports Server (NTRS)

Logan, K. E. (Inventor)

1983-01-01

A flashlamp drive circuit is described which uses an unsaturated transistor as a current mode switch to periodically subject a partially ionized gaseous laser excitation flashlamp to a stable, rectangular pulse of current from an incomplete discharge of an energy storage capacitor. A monostable multivibrator sets the pulse interval, initiating the pulse in response to a flash command by providing a reference voltage to a non-inverting terminal of a base drive amplifier; a tap on an emitter resistor provides a feedback signal sensitive to the current amplitude to an inverting terminal of amplifier, thereby controlling the pulse amplitude. The circuit drives the flashlamp to provide a squarewave current flashlamp discharge.

Measurement and analysis of time-domain characteristics of corona-generated radio interference from a single positive corona source

NASA Astrophysics Data System (ADS)

Li, Xuebao; Li, Dayong; Chen, Bo; Cui, Xiang; Lu, Tiebing; Li, Yinfei

2018-04-01

The corona-generated electromagnetic interference commonly known as radio interference (RI) has become a limiting factor for the design of high voltage direct current transmission lines. In this paper, a time-domain measurement system is developed to measure the time-domain characteristics of corona-generated RI from a single corona source under a positive corona source. In the experiments, the corona current pulses are synchronously measured through coupling capacitors. The one-to-one relationship between the corona current pulse and measured RI voltage pulse is observed. The statistical characteristics of pulse parameters are analyzed, and the correlations between the corona current pulse and RI voltage pulse in the time-domain and frequency-domain are analyzed. Depending on the measured corona current pulses, the time-domain waveform of corona-generated RI is calculated on the basis of the propagation model of corona current on the conductor, the dipolar model for electric field calculation, and the antenna model for inducing voltage calculation. The well matched results between measured and simulated waveforms of RI voltage can show the validity of the measurement and calculation method presented in this paper, which also further show the close correlation between corona current and corona-generated RI.

Three-Signal Method for Accurate Measurements of Depolarization Ratio with Lidar

NASA Technical Reports Server (NTRS)

Reichardt, Jens; Baumgart, Rudolf; McGee, Thomsa J.

2003-01-01

A method is presented that permits the determination of atmospheric depolarization-ratio profiles from three elastic-backscatter lidar signals with different sensitivity to the state of polarization of the backscattered light. The three-signal method is insensitive to experimental errors and does not require calibration of the measurement, which could cause large systematic uncertainties of the results, as is the case in the lidar technique conventionally used for the observation of depolarization ratios.

Inhibitory phosphorylation of GSK-3 by CaMKII couples depolarization to neuronal survival.

PubMed

Song, Bin; Lai, Bingquan; Zheng, Zhihao; Zhang, Yuying; Luo, Jingyan; Wang, Chong; Chen, Yuan; Woodgett, James R; Li, Mingtao

2010-12-24

Glycogen synthase kinase-3 (GSK-3) plays a critical role in neuronal apoptosis. The two mammalian isoforms of the kinase, GSK-3α and GSK-3β, are inhibited by phosphorylation at Ser-21 and Ser-9, respectively. Depolarization, which is vital for neuronal survival, causes both an increase in Ser-21/9 phosphorylation and an inhibition of GSK-3α/β. However, the role of GSK-3 phosphorylation in depolarization-dependent neuron survival and the signaling pathway contributing to GSK-3 phosphorylation during depolarization remain largely unknown. Using several approaches, we showed that both isoforms of GSK-3 are important for mediating neuronal apoptosis. Nonphosphorylatable GSK-3α/β mutants (S21A/S9A) promoted apoptosis, whereas a peptide encompassing Ser-9 of GSK-3β protected neurons in a phosphorylation-dependent manner; these results indicate a critical role for Ser-21/9 phosphorylation on depolarization-dependent neuron survival. We found that Ser-21/9 phosphorylation of GSK-3 was mediated by Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) but not by Akt/PKB, PKA, or p90(RSK). CaMKII associated with and phosphorylated GSK-3α/β. Furthermore, the pro-survival effect of CaMKII was mediated by GSK-3 phosphorylation and inactivation. These findings identify a novel Ca(2+)/calmodulin/CaMKII/GSK-3 pathway that couples depolarization to neuronal survival.

Sequential depolarization of root cortical and stelar cells induced by an acute salt shock - implications for Na(+) and K(+) transport into xylem vessels.

PubMed

Wegner, Lars H; Stefano, Giovanni; Shabala, Lana; Rossi, Marika; Mancuso, Stefano; Shabala, Sergey

2011-05-01

Early events in NaCl-induced root ion and water transport were investigated in maize (Zea mays L) roots using a range of microelectrode and imaging techniques. Addition of 100 mm NaCl to the bath resulted in an exponential drop in root xylem pressure, rapid depolarization of trans-root potential and a transient drop in xylem K(+) activity (A(K+) ) within ∼1 min after stress onset. At this time, no detectable amounts of Na(+) were released into the xylem vessels. The observed drop in A(K+) was unexpected, given the fact that application of the physiologically relevant concentrations of Na(+) to isolated stele has caused rapid plasma membrane depolarization and a subsequent K(+) efflux from the stelar tissues. This controversy was explained by the difference in kinetics of NaCl-induced depolarization between cortical and stelar cells. As root cortical cells are first to be depolarized and lose K(+) to the environment, this is associated with some K(+) shift from the stelar symplast to the cortex, resulting in K(+) being transiently removed from the xylem. Once Na(+) is loaded into the xylem (between 1 and 5 min of root exposure to NaCl), stelar cells become more depolarized, and a gradual recovery in A(K+) occurs. © 2011 Blackwell Publishing Ltd.

Hyperpolarizing and age-dependent depolarizing responses of cultured locus coeruleus neurons to noradrenaline.

PubMed

Finlayson, P G; Marshall, K C

1984-08-01

The electrical activity and responses to noradrenaline (NA) of locus coeruleus (LC) neurons have been studied in organotypic cultures using intracellular recording. Most LC neurons were predominantly quiescent, though occasional bursts of activity were observed; a few cells were tonically active at rates of 0.5-5/s. In most cells tested, iontophoretic application of NA evoked responses which were initially hyperpolarizing, sometimes followed by a depolarizing phase and frequently followed by a period of increased excitatory synaptic activity. The enhanced synaptic activity appeared to be an indirect effect since it was blocked by bath application of tetrodotoxin (TTX). In the presence of TTX, responses to NA of all but one cell were simple hyperpolarizations or biphasic (hyperpolarization/depolarization) responses. The presence of the depolarizing component appeared to be age-dependent, since it was frequently observed in cultures grown in vitro for less than 26 days, while neurons in older cultures exhibited only hyperpolarizing responses. If such age-dependent depolarizing responses are present in vivo, they would represent a unique example of a transmitter response which is present only during a transient developmental phase.

Chloride channel blockers promote relaxation of TEA-induced contraction in airway smooth muscle.

PubMed

Yim, Peter D; Gallos, George; Perez-Zoghbi, Jose F; Trice, Jacquelyn; Zhang, Yi; Siviski, Matthew; Sonett, Joshua; Emala, Charles W

2013-01-01

Enhanced airway smooth muscle (ASM) contraction is an important component in the pathophysiology of asthma. We have shown that ligand gated chloride channels modulate ASM contractile tone during the maintenance phase of an induced contraction, however the role of chloride flux in depolarization-induced contraction remains incompletely understood. To better understand the role of chloride flux under these conditions, muscle force (human ASM, guinea pig ASM), peripheral small airway luminal area (rat ASM) and airway smooth muscle plasma membrane electrical potentials (human cultured ASM) were measured. We found ex vivo guinea pig airway rings, human ASM strips and small peripheral airways in rat lungs slices relaxed in response to niflumic acid following depolarization-induced contraction induced by K(+) channel blockade with tetraethylammonium chloride (TEA). In isolated human airway smooth muscle cells TEA induce depolarization as measured by a fluorescent indicator or whole cell patch clamp and this depolarization was reversed by niflumic acid. These findings demonstrate that ASM depolarization induced contraction is dependent on chloride channel activity. Targeting of chloride channels may be a novel approach to relax hypercontractile airway smooth muscle in bronchoconstrictive disorders.

Ground-based lidar measurements from Ny-Ålesund during ASTAR 2007

NASA Astrophysics Data System (ADS)

Hoffmann, A.; Ritter, C.; Stock, M.; Shiobara, M.; Lampert, A.; Maturilli, M.; Orgis, T.; Neuber, R.; Herber, A.

2009-11-01

During the Arctic Study of Tropospheric Aerosol, Clouds and Radiation (ASTAR) in March and April 2007, measurements obtained at the AWIPEV Arctic Research Base in Ny-Ålesund, Spitsbergen at 78.9° N, 11.9° E (operated by the Alfred Wegener Institute for Polar and Marine Research - AWI and the Institut polaire français Paul-Emile Victor - IPEV), supported the airborne campaign. This included lidar data from the Koldewey Aerosol Raman Lidar (KARL) and the Micro Pulse Lidar (MPL), located in the atmospheric observatory as well as photometer data and the daily launched radiosonde. The MPL features nearly continuous measurements; the KARL was switched on whenever weather conditions allowed observations (145 h in 61 days). From 1 March to 30 April, 71 meteorological balloon soundings were performed and compared with the concurrent MPL measurements; photometer measurements are available from 18 March. For the KARL data, a statistical overview of particle detection based on their optical properties backscatter ratio and volume depolarization can be given. The altitudes of the occurrence of the named features (subvisible and visible ice and water as well as mixed-phase clouds, aerosol layers) as well as their dependence on different air mass origins are analyzed. Although the spring 2007 was characterized by rather clean conditions, diverse case studies of cloud and aerosol occurrence during March and April 2007 are presented in more detail, including temporal development and main optical properties as depolarization, backscatter and extinction coefficients. Links between air mass origins and optical properties can be presumed but need further evidence.