Properties and ionic mechanisms of action potential adaptation, restitution, and accommodation in canine epicardium.

PubMed

Decker, Keith F; Heijman, Jordi; Silva, Jonathan R; Hund, Thomas J; Rudy, Yoram

2009-04-01

Computational models of cardiac myocytes are important tools for understanding ionic mechanisms of arrhythmia. This work presents a new model of the canine epicardial myocyte that reproduces a wide range of experimentally observed rate-dependent behaviors in cardiac cell and tissue, including action potential (AP) duration (APD) adaptation, restitution, and accommodation. Model behavior depends on updated formulations for the 4-aminopyridine-sensitive transient outward current (I(to1)), the slow component of the delayed rectifier K(+) current (I(Ks)), the L-type Ca(2+) channel current (I(Ca,L)), and the Na(+)-K(+) pump current (I(NaK)) fit to data from canine ventricular myocytes. We found that I(to1) plays a limited role in potentiating peak I(Ca,L) and sarcoplasmic reticulum Ca(2+) release for propagated APs but modulates the time course of APD restitution. I(Ks) plays an important role in APD shortening at short diastolic intervals, despite a limited role in AP repolarization at longer cycle lengths. In addition, we found that I(Ca,L) plays a critical role in APD accommodation and rate dependence of APD restitution. Ca(2+) entry via I(Ca,L) at fast rate drives increased Na(+)-Ca(2+) exchanger Ca(2+) extrusion and Na(+) entry, which in turn increases Na(+) extrusion via outward I(NaK). APD accommodation results from this increased outward I(NaK). Our simulation results provide valuable insight into the mechanistic basis of rate-dependent phenomena important for determining the heart's response to rapid and irregular pacing rates (e.g., arrhythmia). Accurate simulation of rate-dependent phenomena and increased understanding of their mechanistic basis will lead to more realistic multicellular simulations of arrhythmia and identification of molecular therapeutic targets.

Activation of outward K+ currents: effect of VIP in oesophagus

PubMed Central

Jury, Jennifer; Daniel, Edwin E

1999-01-01

Electrical field stimulations (EFS) of the opossum and canine lower oesophageal sphincters (OLOS and CLOS respectively) and opossum oesophageal body circular muscle (OOBCM) induce non-adrenergic, non-cholinergic (NANC) relaxations of any active tension and NO-mediated hyperpolarization. VIP relaxes the OLOS and CLOS and any tone in OOBCM without major electrophysiological effects. These relaxations are not blocked by NOS inhibitors. Using isolated smooth muscle cells, we tested whether VIP acted through myogenic NO production.Outward currents were similar in OOBCM and OLOS and NO increased them regardless of pipette Ca2+i, from 50–8000 nM. L-NAME or L-NOARG did not block outward currents in OLOS at 200 nM pipette Ca2+.Outward currents in CLOS cells decreased at 200 nM pipette Ca2+ or less but NO donors still increased them. VIP had no effect on outward currents in cells from OOBCM, OLOS or CLOS under conditions of pipette Ca2+ at which NO donors increased outward K+ currents.We conclude, VIP does not mimic electrophysiological effects of NO donors on isolated cells of OOBCM, OLOS or CLOS. VIP relaxes the OLOS and CLOS and inhibits contraction of OOBCM by a mechanism unrelated to release of myogenic NO or an increase in outward current.Also, the different dependence of outward currents of OOBCM and OLOS on pipette Ca2+ from those of CLOS suggests that different K+ channels are involved and that myogenic NO production contributes to K+ channel activity in CLOS but not in OLOS or OOBCM. PMID:10385258

Separation of the pace-maker and plateau components of delayed rectification in cardiac Purkinje fibres

PubMed Central

Hauswirth, O.; Noble, D.; Tsien, R. W.

1972-01-01

1. Experiments on sheep Purkinje fibres were designed to determine whether the current mechanisms responsible for delayed rectification at the pace-maker (negative to -50 mV) and plateau (positive to -50 mV) ranges of potential are kinetically separable and independent. 2. Hyperpolarizations from the plateau range were shown to produce decay of a single component of outward current within the plateau range, but two components were evident when the hyperpolarizations entered the pace-maker range. 3. The time courses of recovery of the two components were too similar at -25 mV to allow temporal resolution at this potential. Clear temporal resolution was, however, possible at potentials between -55 and -95 mV. An indirect method of resolving the two components at -25 mV was used. 4. The kinetic properties of the two components correspond to those previously described for the pace-maker potassium current, iK2, and the outward plateau current, ix1 (Noble & Tsien, 1968, 1969a). 5. The instantaneous (fully activated) current—voltage relation for iK2 was reconstructed from the analysed current records. It was found that this relation shows a negative slope conductance at all potentials positive to -75 mV and that the current tends towards zero at zero membrane potential. 6. The results are compared with those predicted by two reaction models of the iK2 and ix1 mechanisms. It is concluded that iK2 and ix1 are kinetically separable but that it is not possible with present techniques to decide whether they are controlled by the same or completely independent membrane structures. It is also shown that the instantaneous current—voltage relation calculated for iK2 does not depend on whether the controlling mechanisms are assumed to be independent or linked. PMID:4679715

Transient voltage-dependent potassium currents are reduced in NTS neurons isolated from renal wrap hypertensive rats.

PubMed

Belugin, Sergei; Mifflin, Steve

2005-12-01

Whole cell patch-clamp measurements were made in neurons enzymatically dispersed from the nucleus of the solitary tract (NTS) to determine if alterations occur in voltage-dependent potassium channels from rats made hypertensive (HT) by unilateral nephrectomy/renal wrap for 4 wk. Some rats had the fluorescent tracer DiA applied to the aortic nerve before the experiment to identify NTS neurons receiving monosynaptic baroreceptor afferent inputs. Mean arterial pressure (MAP) was greater in 4-wk HT (165 +/- 5 mmHg, n = 26, P < 0.001) rats compared with normotensive (NT) rats (109 +/- 3 mmHg measured in 10 of 69 rats). Transient outward currents (TOCs) were observed in 67-82% of NTS neurons from NT and HT rats. At activation voltages from -10 to +10 mV, TOCs were significantly less in HT neurons compared with those observed in NT neurons (P < 0.001). There were no differences in the voltage-dependent activation kinetics, the voltage dependence of steady-state inactivation, and the rise and decay time constants of the TOCs comparing neurons isolated from NT and HT rats. The 4-aminopyridine-sensitive component of the TOC was significantly less in neurons from HT compared with NT rats (P < 0.001), whereas steady-state outward currents, whether or not sensitive to 4-aminopyridine or tetraethylammonium, were not different. Delayed excitation, studied under current clamp, was observed in 60-80% of NTS neurons from NT and HT rats and was not different comparing neurons from NT and HT rats. However, examination of the subset of NTS neurons exhibiting somatic DiA fluorescence revealed that DiA-labeled neurons from HT rats had a significantly shorter duration delayed excitation (n = 8 cells, P = 0.022) than DiA-labeled neurons from NT rats (n = 7 cells). Neurons with delayed excitation from HT rats had a significantly broader first action potential (AP) and a slower maximal downstroke velocity of repolarization compared with NT neurons with delayed excitation (P = 0.016 and P = 0.014, respectively). The number of APs in the first 200 ms of a sustained depolarization was greater in HT than NT neurons (P = 0.012). These results suggest that HT of 4-wk duration reduces TOCs in NTS neurons, and this contributes to reduced delayed excitation and increased AP responses to depolarizing inputs. Such changes could alter baroreflex function in hypertension.

Regulation of the instantaneous inward rectifier and the delayed outward rectifier potassium channels by Captopril and Angiotensin II via the Phosphoinositide-3 kinase pathway in volume-overload-induced hypertrophied cardiac myocytes.

PubMed

Alvin, Zikiar V; Laurence, Graham G; Coleman, Bernell R; Zhao, Aiqiu; Hajj-Moussa, Majd; Haddad, Georges E

2011-07-01

Early development of cardiac hypertrophy may be beneficial but sustained hypertrophic activation leads to myocardial dysfunction. Regulation of the repolarizing currents can be modulated by the activation of humoral factors, such as angiotensin II (ANG II) through protein kinases. The aim of this work is to assess the regulation of IK and IK1 by ANG II through the PI3-K pathway in hypertrophied ventricular myocytes. Cardiac eccentric hypertrophy was induced through volume-overload in adult male rats by aorto-caval shunt (3 weeks). After one week half of the rats were given captopril (2 weeks; 0.5 g/l/day) and the other half served as control. The voltage-clamp and western blot techniques were used to measure the delayed outward rectifier potassium current (IK) and the instantaneous inward rectifier potassium current (IK1) and Akt activity, respectively. Hypertrophied cardiomyocytes showed reduction in IK and IK1. Treatment with captopril alleviated this difference seen between sham and shunt cardiomyocytes. Acute administration of ANG II (10-6M) to cardiocytes treated with captopril reduced IK and IK1 in shunts, but not in sham. Captopril treatment reversed ANG II effects on IK and IK1 in a PI3-K-independent manner. However in the absence of angiotensin converting enzyme inhibition, ANG II increased both IK and IK1 in a PI3-K-dependent manner in hypertrophied cardiomyocytes. Thus, captopril treatment reveals a negative effect of ANG II on IK and IK1, which is PI3-K independent, whereas in the absence of angiotensin converting enzyme inhibition IK and IK1 regulation is dependent upon PI3-K.

Equatorial potassium currents in lenses.

PubMed

Wind, B E; Walsh, S; Patterson, J W

1988-02-01

Earlier work with the vibrating probe demonstrated the existence of outward potassium currents at the equator and inward sodium currents at the optical poles of the lens. By adding microelectrodes to the system, it is possible to relate steady currents (J) to the potential difference (PD) measured with a microelectrode. By injecting an outward current (I), it is possible to determine resistances and also the PD at which the steady outward potassium current becomes zero (PDJ = 0). At this PD the concentration gradient for potassium efflux and the electrical gradient for potassium influx are balanced so that there is no net flow of potassium across the membranes associated with the production of J. The PDJ = 0 for 18 rat lenses was 86 mV and that for 12 frogs lenses was -95 mV. This agrees with the potassium equilibrium potential and provides strong evidence to support the view that the outward equatorial current, J, is a potassium current. With the injection of outward current, I, the PD becomes more negative, the outward equatorial current, J, decreases, and the inward current at the optical poles increases. This suggests that there are separate electrical loops for K+ and Na+ that are partially linked by the Na, K-pump. Using Ohm's law, it is possible to calculate the input resistance (R = delta PD/I), the resistance related to the production of J (RJ = delta PD/delta J), and the effect of the combined resistances (delta J/I). The driving force for J can be estimated (PDJ = 0-PD). The relationships among currents, voltages and resistance can be used to determine the characteristics of the membranes that are associated with the outward potassium current observed at the equator. The effects of graded deformation of the lens were determined. The effects were reversible. The sites of inward and outward currents were not altered. Following deformation, the equatorial current, J, increased, and the PD became less negative. The PDJ = 0 remains the same so the ratio of K+ concentrations across the membrane responsible for J is unchanged. Therefore, the decrease in PD is ascribed to an increase in Na+ permeance with a resultant increase in driving force accounting for the increase in J.

Ionic mechanisms of action of prion protein fragment PrP(106-126) in rat basal forebrain neurons.

PubMed

Alier, Kwai; Li, Zongming; Mactavish, David; Westaway, David; Jhamandas, Jack H

2010-08-01

Prion diseases are neurodegenerative disorders that are characterized by the presence of the misfolded prion protein (PrP). Neurotoxicity in these diseases may result from prion-induced modulation of ion channel function, changes in neuronal excitability, and consequent disruption of cellular homeostasis. We therefore examined PrP effects on a suite of potassium (K(+)) conductances that govern excitability of basal forebrain neurons. Our study examined the effects of a PrP fragment [PrP(106-126), 50 nM] on rat neurons using the patch clamp technique. In this paradigm, PrP(106-126) peptide, but not the "scrambled" sequence of PrP(106-126), evoked a reduction of whole-cell outward currents in a voltage range between -30 and +30 mV. Reduction of whole-cell outward currents was significantly attenuated in Ca(2+)-free external media and also in the presence of iberiotoxin, a blocker of calcium-activated potassium conductance. PrP(106-126) application also evoked a depression of the delayed rectifier (I(K)) and transient outward (I(A)) potassium currents. By using single cell RT-PCR, we identified the presence of two neuronal chemical phenotypes, GABAergic and cholinergic, in cells from which we recorded. Furthermore, cholinergic and GABAergic neurons were shown to express K(v)4.2 channels. Our data establish that the central region of PrP, defined by the PrP(106-126) peptide used at nanomolar concentrations, induces a reduction of specific K(+) channel conductances in basal forebrain neurons. These findings suggest novel links between PrP signalling partners inferred from genetic experiments, K(+) channels, and PrP-mediated neurotoxicity.

Relation of Field-Aligned Currents Measured by the Network of Iridium® Spacecraft to Solar Wind and Substorms

NASA Astrophysics Data System (ADS)

McPherron, R. L.; Anderson, B. J.; Chu, Xiangning

2018-03-01

The strength of field-aligned currents coupling the magnetosphere to the ionosphere was obtained by the Active Magnetosphere and Planetary Electrodynamics Response Experiment (AMPERE) using the network of Iridium® spacecraft. The distribution of current was integrated giving total current in and out of the ionosphere on the dayside and nightside of the Earth in both hemispheres. The onset of auroral zone negative bays and midlatitude positive bays corresponds to an increase in nightside upward current. The total outward current tends toward saturation with increasing solar wind driver strength. The optimum solar wind coupling function for AL index predicts 73% of the variance in nightside upward current. The dayside and nightside predictors of upward current rise to a peak at 30-45 min and decay slowly over 2.5 hr. Nightside response is delayed relative to dayside.

Characterization of ionic currents of cells of the subfornical organ that project to the supraoptic nuclei

NASA Technical Reports Server (NTRS)

Johnson, R. F.; Beltz, T. G.; Jurzak, M.; Wachtel, R. E.; Johnson, A. K.

1999-01-01

The subfornical organ (SFO) is a forebrain structure that converts peripheral blood-borne signals reflecting the hydrational state of the body to neural signals and then through efferent fibers conveys this information to several central nervous system structures. One of the forebrain areas receiving input from the SFO is the supraoptic nucleus (SON), a source of vasopressin synthesis and control of release from the posterior pituitary. Little is known of the transduction and transmission processes by which this conversion of systemic information to brain input occurs. As a step in elucidating these mechanisms, the present study characterized the ionic currents of dissociated cells of the SFO that were identified as neurons that send efferents to the SON. A retrograde tracer was injected into the SON area in eleven-day-old rats. After three days for retrograde transport of the label, the SFOs of these animals were dissociated and plated for tissue culture. The retrograde tracer was used to identify the soma of SFO cells projecting to the SON so that voltage-dependent ionic currents using whole-cell voltage clamp methods could be studied. The three types of currents in labeled SFO neurons were characterized as a 1) rapid, transient inward current that can be blocked by tetrodotoxin (TTX) characteristic of a sodium current; 2) slow-onset sustained outward current that can be blocked by tetraethylammonium (TEA) characteristic of a delayed rectifier potassium current; and 3) remaining outward current that has a rapid-onset and transient characteristic of a potassium A-type current. Copyright 1999 Elsevier Science B.V.

Extracellular matrix of collagen modulates arrhythmogenic activity of pulmonary veins through p38 MAPK activation.

PubMed

Lu, Yen-Yu; Chen, Yao-Chang; Kao, Yu-Hsun; Chen, Shih-Ann; Chen, Yi-Jen

2013-06-01

Atrial fibrillation (AF) is the most common sustained arrhythmia. Cardiac fibrosis with enhanced extracellular collagen plays a critical role in the pathophysiology of AF through structural and electrical remodeling. Pulmonary veins (PVs) are important foci for AF genesis. The purpose of this study was to evaluate whether collagen can directly modulate PV arrhythmogenesis. Action potentials and ionic currents were investigated in isolated male New Zealand rabbit PV cardiomyocytes with and without collagen incubation (10μg/ml, 5-7h) using the whole-cell patch-clamp technique. Compared to control PV cardiomyocytes (n=25), collagen-treated PV cardiomyocytes (n=22) had a faster beating rate (3.2±04 vs. 1.9±0.2Hz, p<0.005) and a larger amplitude of delayed afterdepolarization (16±2 vs. 10±1mV, p<0.01). Moreover, collagen-treated PV cardiomyocytes showed a larger transient outward potassium current, small-conductance Ca(2+)-activated K(+) current, inward rectifier potassium current, pacemaker current, and late sodium current than control PV cardiomyocytes, but amplitudes of the sodium current, sustained outward potassium current, and L-type calcium current were similar. Collagen increased the p38 MAPK phosphorylation in PV cardiomyocytes as compared to control. The change of the spontaneous activity and action potential morphology were ameliorated by SB203580 (the p38 MAPK catalytic activity inhibitor), indicating that collagen can directly increase PV cardiomyocyte arrhythmogenesis through p38 MAPK activation, which may contribute to the pathogenesis of AF. Copyright © 2013 Elsevier Ltd. All rights reserved.

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.

Delayed rectifier and A-type potassium channels associated with Kv 2.1 and Kv 4.3 expression in embryonic rat neural progenitor cells.

PubMed

Smith, Dean O; Rosenheimer, Julie L; Kalil, Ronald E

2008-02-13

Because of the importance of voltage-activated K(+) channels during embryonic development and in cell proliferation, we present here the first description of these channels in E15 rat embryonic neural progenitor cells derived from the subventricular zone (SVZ). Activation, inactivation, and single-channel conductance properties of recorded progenitor cells were compared with those obtained by others when these Kv gene products were expressed in oocytes. Neural progenitor cells derived from the subventricular zone of E15 embryonic rats were cultured under conditions that did not promote differentiation. Immunocytochemical and Western blot assays for nestin expression indicated that almost all of the cells available for recording expressed this intermediate filament protein, which is generally accepted as a marker for uncommitted embryonic neural progenitor cells. However, a very small numbers of the cells expressed GFAP, a marker for astrocytes, O4, a marker for immature oligodendrocytes, and betaIII-tubulin, a marker for neurons. Using immunocytochemistry and Western blots, we detected consistently the expression of Kv2.1, and 4.3. In whole-cell mode, we recorded two outward currents, a delayed rectifier and an A-type current. We conclude that Kv2.1, and 4.3 are expressed in E15 SVZ neural progenitor cells, and we propose that they may be associated with the delayed-rectifier and the A-type currents, respectively, that we recorded. These results demonstrate the early expression of delayed rectifier and A-type K(+) currents and channels in embryonic neural progenitor cells prior to the differentiation of these cells.

Regional analysis of whole cell currents from hair cells of the turtle posterior crista.

PubMed

Brichta, Alan M; Aubert, Anne; Eatock, Ruth Anne; Goldberg, Jay M

2002-12-01

The turtle posterior crista is made up of two hemicristae, each consisting of a central zone containing type I and type II hair cells and a surrounding peripheral zone containing only type II hair cells and extending from the planum semilunatum to the nonsensory torus. Afferents from various regions of a hemicrista differ in their discharge properties. To see if afferent diversity is related to the basolateral currents of the hair cells innervated, we selectively harvested type I and II hair cells from the central zone and type II hair cells from two parts of the peripheral zone, one near the planum and the other near the torus. Voltage-dependent currents were studied with the whole cell, ruptured-patch method and characterized in voltage-clamp mode. We found regional differences in both outwardly and inwardly rectifying voltage-sensitive currents. As in birds and mammals, type I hair cells have a distinctive outwardly rectifying current (I(K,L)), which begins activating at more hyperpolarized voltages than do the outward currents of type II hair cells. Activation of I(K,L) is slow and sigmoidal. Maximal outward conductances are large. Outward currents in type II cells vary in their activation kinetics. Cells with fast kinetics are associated with small conductances and with partial inactivation during 200-ms depolarizing voltage steps. Almost all type II cells in the peripheral zone and many in the central zone have fast kinetics. Some type II cells in the central zone have large outward currents with slow kinetics and little inactivation. Although these currents resemble I(K,L), they can be distinguished from the latter both electrophysiologically and pharmacologically. There are two varieties of inwardly rectifying currents in type II hair cells: activation of I(K1) is rapid and monoexponential, whereas that of I(h) is slow and sigmoidal. Many type II cells either have both inward currents or only have I(K1); very few cells only have I(h). Inward currents are less conspicuous in type I cells. Type II cells near the torus have smaller outwardly rectifying currents and larger inwardly rectifying currents than those near the planum, but the differences are too small to account for variations in discharge properties of bouton afferents innervating the two regions of the peripheral zone. The large outward conductances seen in central cells, by lowering impedances, may contribute to the low rotational gains of some central-zone afferents.

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).

Activity of Palythoa caribaeorum Venom on Voltage-Gated Ion Channels in Mammalian Superior Cervical Ganglion Neurons.

PubMed

Lazcano-Pérez, Fernando; Castro, Héctor; Arenas, Isabel; García, David E; González-Muñoz, Ricardo; Arreguín-Espinosa, Roberto

2016-05-05

The Zoanthids are an order of cnidarians whose venoms and toxins have been poorly studied. Palythoa caribaeorum is a zoanthid commonly found around the Mexican coastline. In this study, we tested the activity of P. caribaeorum venom on voltage-gated sodium channel (NaV1.7), voltage-gated calcium channel (CaV2.2), the A-type transient outward (IA) and delayed rectifier (IDR) currents of KV channels of the superior cervical ganglion (SCG) neurons of the rat. These results showed that the venom reversibly delays the inactivation process of voltage-gated sodium channels and inhibits voltage-gated calcium and potassium channels in this mammalian model. The compounds responsible for these effects seem to be low molecular weight peptides. Together, these results provide evidence for the potential use of zoanthids as a novel source of cnidarian toxins active on voltage-gated ion channels.

Activity of Palythoa caribaeorum Venom on Voltage-Gated Ion Channels in Mammalian Superior Cervical Ganglion Neurons

PubMed Central

Lazcano-Pérez, Fernando; Castro, Héctor; Arenas, Isabel; García, David E.; González-Muñoz, Ricardo; Arreguín-Espinosa, Roberto

2016-01-01

The Zoanthids are an order of cnidarians whose venoms and toxins have been poorly studied. Palythoa caribaeorum is a zoanthid commonly found around the Mexican coastline. In this study, we tested the activity of P. caribaeorum venom on voltage-gated sodium channel (NaV1.7), voltage-gated calcium channel (CaV2.2), the A-type transient outward (IA) and delayed rectifier (IDR) currents of KV channels of the superior cervical ganglion (SCG) neurons of the rat. These results showed that the venom reversibly delays the inactivation process of voltage-gated sodium channels and inhibits voltage-gated calcium and potassium channels in this mammalian model. The compounds responsible for these effects seem to be low molecular weight peptides. Together, these results provide evidence for the potential use of zoanthids as a novel source of cnidarian toxins active on voltage-gated ion channels. PMID:27164140

Reduction of I(Ca,L) and I(to1) density in hypertrophied right ventricular cells by simulated high altitude in adult rats.

PubMed

Chouabe, C; Espinosa, L; Megas, P; Chakir, A; Rougier, O; Freminet, A; Bonvallet, R

1997-01-01

The present paper describes the effect of a simulated hypobaric condition (at the altitude of 4500 m) on morphological characteristics and on some ionic currents in ventricular cells of adult rats. According to current data, chronic high-altitude exposure led to mild right ventricular hypertrophy. Increase in right ventricular weight appeared to be due wholly or partly to an enlargement of myocytes. The whole-cell patch-clamp technique was used and this confirmed, by cell capacitance measurement, that chronic high-altitude exposure induced an increase in the size of the right ventricular cells. Hypertrophied cells showed prolongation of action potential (AP). Four ionic currents, playing a role along with many others in the precise balance of inward and outward currents that control the duration of cardiac AP, were investigated. We report a significant decrease in the transient outward (I(to1)) and in the L-type calcium current (I(Ca,L)) densities while there was no significant difference in the delayed rectifier current (I(K)) or in the inward rectifier current (I(K1)) densities in hypertrophied right ventricular cells compared to control cells. At a given potential the decrease in I(to 1) density was relatively more important than the decrease in I(Ca,L) density. In both cell types, all the currents displayed the same voltage dependence. The inactivation kinetics of I(to 1) and I(Ca,L) or the steady-state activation and inactivation relationships were not significantly modified by chronic high-altitude exposure. We conclude that chronic high-altitude exposure induced true right ventricular myocyte hypertrophy and that the decrease in I(to 1) density might account for the lengthened action potential, or have a partial effect.

Toxic effects of environmental rare earth elements on delayed outward potassium channels and their mechanisms from a microscopic perspective.

PubMed

Wang, Lihong; He, Jingfang; Xia, Ao; Cheng, Mengzhu; Yang, Qing; Du, Chunlei; Wei, Haiyan; Huang, Xiaohua; Zhou, Qing

2017-08-01

The wide applications cause a large amount of rare earth elements (REEs) to be released into the environment, and ultimately into the human body through food chain. Toxic effects of REEs on humans have been extensively studied, but their toxic effects and binding targets in cells are not understood. Delayed outward potassium channels (K + channels) are good targets for exogenous substances or clinical drugs. To evaluate cellular toxicities of REEs and clarify toxic mechanisms, the toxicities of REEs on the K + channel and their structural basis were investigated. The results showed that delayed outward potassium channels on the plasma membrane are the targets of REEs acting on living organisms, and the changes in the thermodynamic and kinetic characteristics of the K + channel are the reasons of diseases induced by REEs. Two types of REEs, a light REE La 3+ and a heavy REE Tb 3+ , displayed different intensity of toxicities on the K + channel, in which the toxicity of Tb 3+ was stronger than that of La 3+ . More interestingly, in comparison with that of heavy metal Cd 2+ , the cytotoxicities of the light and heavy REEs showed discriminative differences, and the cytotoxicity of Tb 3+ was higher than that of Cd 2+ , while the cytotoxicity of La 3+ was lower than that of Cd 2+ . These different cytotoxicities of La 3+ , Tb 3+ and Cd 2+ on human resulted from the varying binding abilities of the metals to this channel protein. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of phloretin and phloridzin on Ca2+ handling, the action potential, and ion currents in rat ventricular myocytes.

PubMed

Olson, Marnie L; Kargacin, Margaret E; Ward, Christopher A; Kargacin, Gary J

2007-06-01

The effects of the phytoestrogens phloretin and phloridzin on Ca(2+) handling, cell shortening, the action potential, and Ca(2+) and K(+) currents in freshly isolated cardiac myocytes from rat ventricle were examined. Phloretin increased the amplitude and area and decreased the rate of decline of electrically evoked Ca(2+) transients in the myocytes. These effects were accompanied by an increase in the Ca(2+) load of the sarcoplasmic reticulum, as determined by the area of caffeine-evoked Ca(2+) transients. An increase in the extent of shortening of the myocytes in response to electrically evoked action potentials was also observed in the presence of phloretin. To further examine possible mechanisms contributing to the observed changes in Ca(2+) handling and contractility, the effects of phloretin on the cardiac action potential and plasma membrane Ca(2+) and K(+) currents were examined. Phloretin markedly increased the action potential duration in the myocytes, and it inhibited the Ca(2+)-independent transient outward K(+) current (I(to)). The inwardly rectifying K(+) current, the sustained outward delayed rectifier K(+) current, and L-type Ca(2+) currents were not significantly different in the presence and absence of phloretin, nor was there any evidence that the Na(+)/Ca(2+) exchanger was affected. The effects of phloretin on Ca(2+) handling in the myocytes are consistent with its effects on I(to). Phloridzin did not significantly alter the amplitude or area of electrically evoked Ca(2+) transients in the myocytes, nor did it have detectable effects on the sarcoplasmic reticulum Ca(2+) load, cell shortening, or the action potential.

Delayed Rectifier and A-Type Potassium Channels Associated with Kv 2.1 and Kv 4.3 Expression in Embryonic Rat Neural Progenitor Cells

PubMed Central

Smith, Dean O.; Rosenheimer, Julie L.; Kalil, Ronald E.

2008-01-01

Background Because of the importance of voltage-activated K+ channels during embryonic development and in cell proliferation, we present here the first description of these channels in E15 rat embryonic neural progenitor cells derived from the subventricular zone (SVZ). Activation, inactivation, and single-channel conductance properties of recorded progenitor cells were compared with those obtained by others when these Kv gene products were expressed in oocytes. Methodology/Principal Findings Neural progenitor cells derived from the subventricular zone of E15 embryonic rats were cultured under conditions that did not promote differentiation. Immunocytochemical and Western blot assays for nestin expression indicated that almost all of the cells available for recording expressed this intermediate filament protein, which is generally accepted as a marker for uncommitted embryonic neural progenitor cells. However, a very small numbers of the cells expressed GFAP, a marker for astrocytes, O4, a marker for immature oligodendrocytes, and βIII-tubulin, a marker for neurons. Using immunocytochemistry and Western blots, we detected consistently the expression of Kv2.1, and 4.3. In whole-cell mode, we recorded two outward currents, a delayed rectifier and an A-type current. Conclusions/Significance We conclude that Kv2.1, and 4.3 are expressed in E15 SVZ neural progenitor cells, and we propose that they may be associated with the delayed-rectifier and the A-type currents, respectively, that we recorded. These results demonstrate the early expression of delayed rectifier and A-type K+ currents and channels in embryonic neural progenitor cells prior to the differentiation of these cells. PMID:18270591

Voltage-dependent ion channels in the mouse RPE: comparison with Norrie disease mice.

PubMed

Wollmann, Guido; Lenzner, Steffen; Berger, Wolfgang; Rosenthal, Rita; Karl, Mike O; Strauss, Olaf

2006-03-01

We studied electrophysiological properties of cultured retinal pigment epithelial (RPE) cells from mouse and a mouse model for Norrie disease. Wild-type RPE cells revealed the expression of ion channels known from other species: delayed-rectifier K(+) channels composed of Kv1.3 subunits, inward rectifier K(+) channels, Ca(V)1.3 L-type Ca(2+) channels and outwardly rectifying Cl(-) channels. Expression pattern and the ion channel characteristics current density, blocker sensitivity, kinetics and voltage-dependence were compared in cells from wild-type and Norrie mice. Although no significant differences were observed, our study provides a base for future studies on ion channel function and dysfunction in transgenic mouse models.

Distribution, expression and functional effects of small conductance Ca-activated potassium (SK) channels in rat myometrium.

PubMed

Noble, Karen; Floyd, Rachel; Shmygol, Andre; Shmygol, Anatoly; Mobasheri, A; Wray, Susan

2010-01-01

Calcium-activated potassium channels are important in a variety of smooth muscles, contributing to excitability and contractility. In the myometrium previous work has focussed on the large conductance channels (BK), and the role of small conductance channels (SK) has received scant attention, despite the finding that over-expression of an SK channel isoform (SK3) results in uterine dysfunction and delayed parturition. This study therefore characterises the expression of the three SK channel isoforms (SK1-3) in rat myometrium throughout pregnancy and investigates their effect on cytosolic [Ca] and force and compares this with that of BK channels. Consistent expression of all SK isoform transcripts and clear immunostaining of SK1-3 was found. Inhibition of SK1-3 channels (apamin, scyllatoxin) significantly inhibited outward current, caused membrane depolarisation and elicited action potentials in previously quiescent cells. Apamin or scyllatoxin increased the amplitude of [Ca] and force in spontaneously contracting myometrial strips throughout gestation. The functional effect of SK inhibition was larger than that of BK channel inhibition. Thus we show for the first time that SK1-3 channels are expressed and translated throughout pregnancy and contribute to outward current, regulate membrane potential and hence Ca signals in pregnant rat myometrium. They contribute more to quiescence that BK channels. 2009 Elsevier Ltd. All rights reserved.

M-currents and other potassium currents in bullfrog sympathetic neurones

PubMed Central

Adams, P. R.; Brown, D. A.; Constanti, A.

1982-01-01

1. Bullfrog lumbar sympathetic neurones were voltage-clamped in vitro through twin micro-electrodes. Four different outward (K+) currents could be identified: (i) a large sustained voltage-sensitive delayed rectifier current (IK) activated at membrane potentials more positive than -25 mV; (ii) a calcium-dependent sustained outward current (IC) activated at similar positive potentials and peaking at +20 to +60 mV; (iii) a transient current (IA) activated at membrane potentials more positive than -60 mV after a hyperpolarizing pre-pulse, but which was rapidly and totally inactivated at all potentials within its activation range; and (iv) a new K+ current, the M-current (IM). 2. IM was detected as a non-inactivating current with a threshold at -60 mV. The underlying conductance GM showed a sigmoidal activation curve between -60 and -10 mV, with half-activation at -35 mV and a maximal value (ḠM) of 84±14 (S.E.M.) nS per neurone. The voltage sensitivity of GM could be expressed in terms of a simple Boltzmann distribution for a single multivalent gating particle. 3. IM activated and de-activated along an exponential time course with a time constant uniquely dependent upon voltage, maximizing at ≃ 150 ms at -35 mV at 22 °C. 4. Instantaneous current—voltage (I/V) curves were approximately linear in the presence of IM, suggesting that the M-channels do not show appreciable rectification. However, the time- and voltage-dependent opening of the M-channels induced considerable rectification in the steady-state I/V curves recorded under both voltage-clamp and current-clamp modes between -60 and -25 mV. Both time- and voltage-dependent rectification in the voltage responses to current injection over this range could be predicted from the kinetic properties of IM. 5. It is suggested that IM exerts a strong potential-clamping effect on the behaviour of these neurones at membrane potentials subthreshold to excitation. PMID:6294290

Cholinergically-induced changes in outward currents in hair cells isolated from the semicircular canal of the frog.

PubMed

Housley, G D; Norris, C H; Guth, P S

1990-01-01

Two cholinergically-induced modulations of membrane conductances have been identified in hair cells isolated from the crista ampullaris of the leopard frog (Rana pipiens), using the whole cell recording configuration of the patch clamp technique. Of 56 crista hair cells tested, 28 showed drug-induced changes in membrane current or membrane potential which were repeatable and could be reversed with washout of drug. The predominant effect (observed in 20 hair cells) of acetylcholine (Ach, 100 microM) to 1mM) or carbachol (1 microM to 50 microM) applied to these hair cells was the reduction of an outward current corresponding to a change in conductance of approximately -0.22 nS. This action by Ach on hair cells has been inferred from previous studies of afferent fiber discharge which reported an increase in firing rate with stimulation of efferent fibers or exogenous application of cholinomimetics (Bernard et al., 1985; Valli et al., 1986; Guth et al., 1986; Norris et al., 1988a). The Ach-induced reduction in outward current was associated with a depolarization of the zero-current membrane potential by approximately +2.5 mV. In a total of 8 hair cells, an Ach-induced reversible increase in outward current was recorded. Changes in conductance were approximately +0.13 nS and were associated with a hyperpolarization of the zero-current membrane potential by approximately -2.2 mV. This current increase is likely to be responsible for the inhibitory post-synaptic potentials (IPSPs) which have previously been recorded intracellularly from acoustico-lateralis hair cells during stimulation of the efferent innervation (Flock and Russell, 1976; Ashmore and Russell, 1982; Art et al., 1984, 1985). Of the remaining 28 hair cells, six cells failed to exhibit any change in membrane conductance or membrane potential in the presence of cholinomimetics while an additional 15 cells exhibited decreases, and 7 cells exhibited increases in outward conductance, during application of Ach or carbachol, which were neither reversible with washout nor repeatable. The Ach-induced decrease in outward current could be reversible blocked by removal of Ca2+ from the external solution. The antagonism of the Ach-induced decrease in outward current by atropine (10(-5) M) suggests that this current may correspond to a facilitatory, 'atropine-preferring' Ach receptor mediated response previously identified in the isolated semicircular canal (Norris et al., 1988a).(ABSTRACT TRUNCATED AT 400 WORDS)

Properties of whole cell currents in isolated olfactory neurons from the chilean toad Caudiverbera caudiverbera.

PubMed

Delgado, R; Labarca, P

1993-06-01

Isolated olfactory neurons from the chilean toad Caudiverbera caudiverbera were found to possess a same set of currents. Outward currents, made of a delayed rectifier and a Ca(2+)-dependent component, were blocked by replacing K+ by Cs+ in the patch pipette, in the presence of millimolar concentrations of tetraethylammonium and 4-aminopyridine in the external solution. Inward currents were made of a transient and a maintained component. The transient was abolished in the absence of external Na+ and was blocked by tetrodotoxin, with an apparent dissociation constant (KDapp) of 25.4 +/- 0.3 nM. The maintained inward currents were suppressed on removing external Ca2+, could be carried also by Ba2+, and were selectively blocked by Cd2+ (KDapp = 3.2 +/- 1.3 microM). A variety of agents found to block the maintained Ca2+ inward currents, including Co2+ and Ni2+, at millimolar concentrations, and nifedipine, verapamil, amiloride, and the amiloride analogue benzamil, at micromolar concentrations, were also effective in either modifying the gating of, or in blocking, the transient inward currents.

[Electrophysiological study on rat conduit pulmonary artery smooth muscle cells under normoxia and acute hypoxia].

PubMed

Hu, Ying; Zou, Fei; Cai, Chun-Qing; Wu, Hang-Yu; Yun, Hai-Xia; Chen, Yun-Tian; Jin, Guo-En; Ge, Ri-Li

2006-10-25

The present study was designed to investigate the electrophysiological characteristics of rat conduit pulmonary artery smooth muscle cells (PASMCs) and the response to acute hypoxia. PASMCs of the 1st to 2nd order branches in the conduit pulmonary arteries were obtained by enzymatic isolation. The PASMCs were divided into acute hypoxia preconditioned group and normoxia group. Hypoxia solutions were achieved by bubbling with 5% CO2 plus 95% N2 for at least 30 min before cell perfusion. Potassium currents were compared between these two groups using whole-cell patch clamp technique. The total outward current of PASMCs was measured under normoxia condition when iBTX [specific blocking agent of large conductance Ca-activated K(+) (BK(Ca)) channel] and 4-AP [specific blocking agent of delayed rectifier K(+) (K(DR)) channel] were added consequently into bath solution. PASMCs were classified into three types according to their size, shape and electrophysiological characteristics. Type I cells are the smallest with spindle shape, smooth surface and discrete perinuclear bulge. Type II cells show the biggest size with banana-like appearance. Type III cells have the similar size with type I, and present intermediary shape between type I and type II. iBTX had little effect on the total outward current in type I cells, while 4-AP almost completely blocked it. Most of the total outward current in type II cells was inhibited by iBTX, and the remaining was sensitive to 4-AP. In type III cells, the total outward current was sensitive to both iBTX and 4-AP. Acute hypoxia reduced the current in all three types of cells: (1614.8+/-62.5) pA to (892.4+/-33.6) pA for type I cells (P<0.01); (438.3+/-42.8) pA to (277.5+/-44.7) pA for type II cells (P<0.01); (1 042.0+/-37.2) pA to (613.6+/-23.8) pA for type III (P<0.01), and raised the resting membrane potentials (E(m)) in all these three types of cells: (-41.6+/-1.6) mV to (-18.6+/-1.5) mV (P<0.01), (-42.3+/-3.8) mV to (-30.6+/-3.0) mV (P<0.01), (-43.3+/-1.6) mV to (-28.4+/-1.4) mV (P<0.01), for type I, II, III cells, respectively. These results suggest that acute hypoxia suppresses the potassium current and improves the E(m) in PASMCs. These effects may be involved in the modulation of constriction/relaxation of conduit artery under acute hypoxia. Different distribution of K(DR) and BK(Ca) channels in these three types of PASMCs might account for their different constriction/relaxation response to acute hypoxia.

Angiotensin II and angiotensin II receptor blocker modulate the arrhythmogenic activity of pulmonary veins.

PubMed

Chen, Yi-Jen; Chen, Yao-Chang; Tai, Ching-Tai; Yeh, Hung-I; Lin, Cheng-I; Chen, Shih-Ann

2006-01-01

Angiotensin II receptor blockers (AIIRBs) have been shown to prevent atrial fibrillation. The pulmonary veins (PVs) are the most important focus for the generation of atrial fibrillation. The aim of this study was to evaluate whether angiotensin II or AIIRB may change the arrhythmogenic activity of the PVs. Conventional microelectrodes and whole-cell patch clamps were used to investigate the action potentials (APs) and ionic currents in isolated rabbit PV tissue and single cardiomyocytes before and after administering angiotensin II or losartan (AIIRB). In the tissue preparations, angiotensin II induced delayed after-depolarizations (1, 10, and 100 nM) and accelerated the automatic rhythm (10 and 100 nM). Angiotensin II (100 nM) prolonged the AP duration and increased the contractile force (10 and 100 nM). Losartan (1 and 10 microM) inhibited the automatic rhythm. Losartan (10 microM) prolonged the AP duration and reduced the contractile force (1 and 10 microM). Angiotensin II reduced the transient outward potassium current (I(to)) but increased the L-type calcium, delayed rectifier potassium (I(K)), transient inward (I(ti)), pacemaker, and Na(+)-Ca(2+) exchanger (NCX) currents in the PV cardiomyocytes. Losartan decreased the I(to), I(K), I(ti), and NCX currents. In conclusion, angiotensin II and AIIRB modulate the PV electrical activity, which may play a role in the pathophysiology of atrial fibrillation.

Neurovascular coupling protects neurons against hypoxic injury via inhibition of potassium currents by generation of nitric oxide in direct neuron and endothelium cocultures.

PubMed

Wu, Kun-Wei; Kou, Zeng-Wei; Mo, Jia-Lin; Deng, Xu-Xu; Sun, Feng-Yan

2016-10-15

This study examined the effect of neuron-endothelial coupling on the survival of neurons after ischemia and the possible mechanism underlying that effect. Whole-cell patch-clamp experiments were performed on cortical neurons cultured alone or directly cocultured with brain microvascular endothelial cells (BMEC). Propidium iodide (PI) and NeuN staining were performed to examine neuronal death following oxygen and glucose deprivation (OGD). We found that the neuronal transient outward potassium currents (I A ) decreased in the coculture system, whereas the outward delayed-rectifier potassium currents (I K ) did not. Sodium nitroprusside, a NO donor, enhanced BMEC-induced I A inhibition and nitro-l-arginine methylester, a NOS inhibitor, partially prevented this inhibition. Moreover, the neurons directly cocultured with BMEC showed more resistance to OGD-induced injury compared with the neurons cultured alone, and that neuroprotective effect was abolished by treatment with NS5806, an activator of the I A . These results indicate that vascular endothelial cells assist neurons to prevent hypoxic injury via inhibiting neuronal I A by production of NO in the direct neuron-BMEC coculture system. These results further provide direct evidence of functional coupling between neurons and vascular endothelial cells. This study clearly demonstrates that vascular endothelial cells play beneficial roles in the pathophysiological processes of neurons after hypoxic injury, suggesting that the improvement of neurovascular coupling or functional remodeling may become an important therapeutic target for preventing brain injury. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Intracellularly applied anti-P70 antibody blocks the induction of abnormal membrane properties by pentylenetetrazole in identified Euhadra neurons.

PubMed

Onozuka, M; Watanabe, K

1996-04-15

Using the voltage-clamp technique combined with pressure injection, we have studied the action of pentylenetetrazole (PTZ) on identified Euhadra neurons by examining how the PTZ-induced changes in membrane properties are affected by an antibody against P70, a protein found in the experimentally-induced epileptogenic cortex of rats. Intracellular injection of anti-P70 antibody blocked the induction by PTZ; bursting activity with both of development of negative slope resistance region in the steady state 1-V curve and a reduction in the delayed outward potassium current. These results suggest a novel mechanism of action for PTZ, involving intracellular protein(s) which react with anti-P70 antibody.

Arctigenin, a potential anti-arrhythmic agent, inhibits aconitine-induced arrhythmia by regulating multi-ion channels.

PubMed

Zhao, Zhenying; Yin, Yongqiang; Wu, Hong; Jiang, Min; Lou, Jianshi; Bai, Gang; Luo, Guo'an

2013-01-01

Arctigenin possesses biological activities, but its underlying mechanisms at the cellular and ion channel levels are not completely understood. Therefore, the present study was designed to identify the anti-arrhythmia effect of arctigenin in vivo, as well as its cellular targets and mechanisms. A rat arrhythmia model was established via continuous aconitine infusion, and the onset times of ventricular premature contraction, ventricular tachycardia and death were recorded. The Action Potential Duration (APD), sodium current (I(Na)), L-type calcium current (I(Ca, L)) and transient outward potassium current (I(to)) were measured and analysed using a patch-clamp recording technique in normal rat cardiomyocytes and myocytes of arrhythmia aconitine-induced by. Arctigenin significantly delayed the arrhythmia onset in the aconitine-induced rat model. The 50% and 90% repolarisations (APD50 and APD90) were shortened by 100 µM arctigenin; the arctigenin dose also inhibited the prolongation of APD50 and APD90 caused by 1 µM aconitine. Arctigenin inhibited I(Na) and I(Ca,L) and attenuated the aconitine-increased I(Na) and I(Ca,L) by accelerating the activation process and delaying the inactivation process. Arctigenin enhanced Ito by facilitating the activation process and delaying the inactivation process, and recoverd the decreased Ito induced by aconitine. Arctigenin has displayed anti-arrhythmia effects, both in vivo and in vitro. In the context of electrophysiology, I(Na), I(Ca, L), and I(to) may be multiple targets of arctigenin, leading to its antiarrhythmic effect. © 2013 S. Karger AG, Basel.

Dissection of K+ currents in Caenorhabditis elegans muscle cells by genetics and RNA interference

PubMed Central

Santi, C. M.; Yuan, A.; Fawcett, G.; Wang, Z.-W.; Butler, A.; Nonet, M. L.; Wei, A.; Rojas, P.; Salkoff, L.

2003-01-01

GFP-promoter experiments have previously shown that at least nine genes encoding potassium channel subunits are expressed in Caenorhabditis elegans muscle. By using genetic, RNA interference, and physiological techniques we revealed the molecular identity of the major components of the outward K+ currents in body wall muscle cells in culture. We found that under physiological conditions, outward current is dominated by the products of only two genes, Shaker (Kv1) and Shal (Kv4), both expressing voltage-dependent potassium channels. Other channels may be held in reserve to respond to particular circumstances. Because GFP-promoter experiments indicated that slo-2 expression is prominent, we created a deletion mutant to identify the SLO-2 current in vivo. In both whole-cell and single-channel modes, in vivo SLO-2 channels were active only when intracellular Ca2+ and Cl- were raised above normal physiological conditions, as occurs during hypoxia. Under such conditions, SLO-2 is the largest outward current, contributing up to 87% of the total current. Other channels are present in muscle, but our results suggest that they are unlikely to contribute a large outward component under physiological conditions. However, they, too, may contribute currents conditional on other factors. Hence, the picture that emerges is of a complex membrane with a small number of household conductances functioning under normal circumstances, but with additional conductances that are activated during unusual circumstances. PMID:14612577

Low-affinity spermine block mediating outward currents through Kir2.1 and Kir2.2 inward rectifier potassium channels

PubMed Central

Ishihara, Keiko; Yan, Ding-Hong

2007-01-01

The outward component of the strong inward rectifier K+ current (IKir) plays a pivotal role in polarizing the membranes of excitable and non-excitable cells and is regulated by voltage-dependent channel block by internal cations. Using the Kir2.1 channel, we previously showed that a small fraction of the conductance susceptible only to a low-affinity mode of block likely carries a large portion of the outward current. To further examine the relevance of the low-affinity block to outward IKir and to explore its molecular mechanism, we studied the block of the Kir2.1 and Kir2.2 channels by spermine, which is the principal Kir2 channel blocker. Current–voltage relations of outward Kir2.2 currents showed a peak, a plateau and two peaks in the presence of 10, 1 and 0.1 μm spermine, respectively, which was explained by the presence of two conductances that differ in their susceptibility to spermine block. When the current–voltage relations showed one peak, like those of native IKir, outward Kir2.2 currents were mediated mostly by the conductance susceptible to the low-affinity block. They also flowed in a narrower range than the corresponding Kir2.1 currents, because of 3- to 4-fold greater susceptibility to the low-affinity block than in Kir2.1. Reducing external [K+] shifted the voltage dependences of both the high- and low-affinity block of Kir2.1 in parallel with the shift in the reversal potential, confirming the importance of the low-affinity block in mediating outward IKir. When Kir2.1 mutants known to have reduced sensitivity to internal blockers were examined, the D172N mutation in the transmembrane pore region made almost all of the conductance susceptible only to low-affinity block, while the E224G mutation in the cytoplasmic pore region reduced the sensitivity to low-affinity block without markedly altering that to the high-affinity block or the high/low conductance ratio. The effects of these mutations support the hypothesis that Kir2 channels exist in two states having different susceptibilities to internal cationic blockers. PMID:17640933

Emerging role of the KCNT1 Slack channel in intellectual disability.

PubMed

Kim, Grace E; Kaczmarek, Leonard K

2014-01-01

The sodium-activated potassium KNa channels Slack and Slick are encoded by KCNT1 and KCNT2, respectively. These channels are found in neurons throughout the brain, and are responsible for a delayed outward current termed I KNa. These currents integrate into shaping neuronal excitability, as well as adaptation in response to maintained stimulation. Abnormal Slack channel activity may play a role in Fragile X syndrome, the most common cause for intellectual disability and inherited autism. Slack channels interact directly with the fragile X mental retardation protein (FMRP) and I KNa is reduced in animal models of Fragile X syndrome that lack FMRP. Human Slack mutations that alter channel activity can also lead to intellectual disability, as has been found for several childhood epileptic disorders. Ongoing research is elucidating the relationship between mutant Slack channel activity, development of early onset epilepsies and intellectual impairment. This review describes the emerging role of Slack channels in intellectual disability, coupled with an overview of the physiological role of neuronal I KNa currents.

Altered transient outward current in human atrial myocytes of patients with reduced left ventricular function.

PubMed

Schreieck, J; Wang, Y; Overbeck, M; Schömig, A; Schmitt, C

2000-02-01

Electrophysiologic remodeling is involved in the self-perpetuation of atrial fibrillation. To define whether differences in atrial electrophysiology already are present in patients with increased susceptibility for atrial fibrillation, we compared patients in sinus rhythm with and without heart failure. Atrial specimens were obtained from patients with reduced left ventricular ejection fraction (LVEF; n = 10) and normal LVEF (n = 16) who were undergoing aortocoronary bypass surgery and from donor hearts (n = 4). Enzymatically isolated atrial myocytes were investigated by whole cell, patch clamp techniques. Total outward current was significantly larger in myocytes of hearts with low LVEF than normal LVEF (19.4 +/- 1.3 vs 15.1 +/- 1.2 pA/pF at pulses to +60 mV, respectively). Analysis of inactivation time courses of different outward current components revealed that the observed current difference is due to the transient calcium-independent outward current I(to1) which is twice as large in the low LVEF group than in the normal LVEF group (9.4 +/- 0.9 vs 4.7 +/- 0.4 pA/pF at pulses to +60 mV, respectively). I(to1) recovery from inactivation was significantly more rapid in myocytes of hearts with low LVEF, and action potential plateau in these cells was significantly shorter. The results of I(to1) and action potential measurements in atrial myocytes of donor hearts were very similar to the results of patients with preserved heart function. I(to1) in human atrial myocytes of patients with reduced LVEF has an increased density and altered kinetics in sinus rhythm. These differences in outward current may explain the reduced plateau phase of action potentials.

GDF15 regulates Kv2.1-mediated outward K+ current through the Akt/mTOR signalling pathway in rat cerebellar granule cells.

PubMed

Wang, Chang-Ying; Huang, An-Qi; Zhou, Meng-Hua; Mei, Yan-Ai

2014-05-15

GDF15 (growth/differentiation factor 15), a novel member of the TGFβ (transforming growth factor β) superfamily, plays critical roles in the central and peripheral nervous systems, but the signal transduction pathways and receptor subtypes involved are not well understood. In the present paper, we report that GDF15 specifically increases the IK (delayed-rectifier outward K+ current) in rat CGNs (cerebellar granule neurons) in time- and concentration-dependent manners. The GDF15-induced amplification of the IK is mediated by the increased expression and reduced lysosome-dependent degradation of the Kv2.1 protein, the main α-subunit of the IK channel. Exposure of CGNs to GDF15 markedly induced the phosphorylation of ERK (extracellular-signal-regulated kinase), Akt and mTOR (mammalian target of rapamycin), but the GDF15-induced IK densities and increased expression of Kv2.1 were attenuated only by Akt and mTOR, and not ERK, inhibitors. Pharmacological inhibition of the Src-mediated phosphorylation of TGFβR2 (TGFβ receptor 2), not TGFβR1, abrogated the effect of GDF15 on IK amplification and Kv2.1 induction. Immunoprecipitation assays showed that GDF15 increased the tyrosine phosphorylation of TGFβRII in the CGN lysate. The results of the present study reveal a novel regulation of Kv2.1 by GDF15 mediated through the TGFβRII-activated Akt/mTOR pathway, which is a previously uncharacterized Smad-independent mechanism of GDF15 signalling.

Physiological basis of a steady endogenous current in rat lumbrical muscle

PubMed Central

1984-01-01

In an attempt to determine the mechanism by which rat skeletal muscle endplates generate a steady outward current, we measured the effects of several drugs (furosemide, bumetanide, 9-anthracene carboxylic acid [9- AC]) and changes in external ion concentration (Na+, K+, Cl-, Ba++) on resting membrane potential (Vm) and on the steady outward current. Each of the following treatments caused a 10-15-mV hyperpolarization of the membrane: replacement of extracellular Cl- with isethionate, addition of furosemide or bumetanide, and addition of 9-AC. These results suggest that Cl- is actively accumulated by the muscle fibers and that the equilibrium potential of Cl- is more positive than the membrane potential. Removal of external Na+ also caused a large hyperpolarization and is consistent with evidence in other tissues that active Cl- accumulation requires external Na+. The same treatments greatly reduced or abolished the steady outward current, with a time course that paralleled the changes in Vm. These results cannot be explained by a model in which the steady outward current is assumed to arise as a result of a nonuniform distribution of Na+ conductance, but they are consistent with models in which the steady current is produced by a nonuniform distribution of GCl or GK. Other treatments (Na+-free and K+-free solutions, and 50 microM BaCl2) caused a temporary reversal of the steady current. Parallel measurements of Vm suggested that in none of these cases did the electrochemical driving force for K+ change sign, which makes it unlikely that the steady current arises as a result of a nonuniform distribution of GK. All of the results, however, are consistent with a model in which the steady outward current arises as a result of a nonuniform distribution of Cl- conductance, with GCl lower near the endplate than in extrajunctional regions. PMID:6325581

Voltage-clamp analysis of membrane currents and excitation-contraction coupling in a crustacean muscle.

PubMed

Weiss, T; Erxleben, C; Rathmayer, W

2001-01-01

A single fibre preparation from the extensor muscle of a marine isopod crustacean is described which allows the analysis of membrane currents and simultaneously recorded contractions under two-electrode voltage-clamp conditions. We show that there are three main depolarisation-gated currents, two are outward and carried by K+, the third is an inward Ca2+ current, I(Ca). Normally, the K+ currents which can be isolated by using K+ channel blockers, mask I(Ca). I(Ca) activates at potentials more positive than -40 mV, is maximal around 0 mV, and shows strong inactivation at higher depolarisation. Inactivation depends on current rather than voltage. Ba2+, Sr2+ and Mg2+ can substitute for Ca2+. Ba2+ currents are about 80% larger than Ca2+ currents and inactivate little. The properties of I(Ca) characterise it as a high threshold L-type current. The outward current consists primarily of a fast, transient A current, I(K(A)) and a maintained, delayed rectifier current, I(K(V)). In some fibres, a small Ca2+-dependent K+ current is also present. I(K(A)) activates fast at depolarisation above -45 mV, shows pronounced inactivation and is almost completely inactivated at holding potentials more positive than -40 mV. I(K(A)) is half-maximally blocked by 70 microM 4-aminopyridine (4-AP), and 70 mM tetraethylammonium (TEA). I(K(V)) activates more slowly, at about -30 mV, and shows no inactivation. It is half-maximally blocked by 2 mM TEA but rather insensitive to 4-AP. Physiologically, the two K+ currents prevent all-or-nothing action potentials and determine the graded amplitude of active electrical responses and associated contractions. Tension development depends on and is correlated with depolarisation-induced Ca2+ influx mediated by I(Ca). The voltage dependence of peak tension corresponds directly to the voltage dependence of the integrated I(Ca). The threshold potential for contraction is at about -38 mV. Peak tension increases with increasing voltage steps, reaches maximum at around 0 mV, and declines with further depolarisation.

Properties of the late transient outward current in isolated intestinal smooth muscle cells of the guinea-pig.

PubMed

Zholos, A V; Baidan, L V; Shuba, M F

1991-11-01

1. Whole-cell membrane currents in voltage-clamped single isolated cells of longitudinal smooth muscle of guinea-pig ileum were studied at room temperature using patch pipettes filled with either high-K+ solution or high-Cs+ solution, to suppress K+ outward current, and containing 0.3 mM-EGTA. 2. In the presence of high-K+ solution in the pipette, membrane depolarization from the holding potential of -50 mV evoked an initial inward calcium current (ICa) followed by a large initial transient outward current and a sustained outward current with spontaneous oscillations superimposed. Prolonged depolarization above -20 mV produced a late transient outward current which reached a maximum (up to several nanoamps at +10 mV) within approximately 1 s and lasted several seconds. 3. The late outward current (ILTO) was voltage dependent and reversed at the EK (potassium equilibrium potential) in cells exposed to high-K+ external solution. It was blocked by TEA+ (tetraethylammonium) or Ba2+ applied externally (calculated Kd (dissociation constant) values were 0.67 and 4.43 mM, respectively) or by high-Cs+ solution perfusing the cell. The removal of extracellular Ca2+, application of Ca2+ channel blockers (3 mM-Co2+, 0.2 mM-Cd2+ or 1 microM-nifedipine) or perfusion of 5 mM-EGTA inside the cell also abolished the current. Thus, the current seems to be a Ca(2+)-activated K+ current. 4. There is a great discrepancy between the time course of the ICa and that of the late ILTO, which suggests that Ca2+ release from intracellular storage sites may contribute to the generation of the ILTO. 5. Bath application of caffeine (10 mM) during the development of ILTO enhanced the current. However, in the presence of caffeine ILTO was inhibited. Moderate inhibition of ICa by caffeine was also observed. 6. Ryanodine (5 microM) applied to the bathing solution completely inhibited ILTO within 3.5 min; however, it had no or little effect on the ICa. 7. Ruthenium Red (10 microM) completely blocked the ILTO and slightly and more slowly inhibited the ICa. 8. Increasing Mg2+ concentration in the pipette solution from 1 to 6 mM abolished the ILTO. 9. It was concluded that the ILTO was activated mainly by Ca2+ released from the intracellular storage sites following Ca2+ entry, presumably by a Ca(2+)-induced Ca2+ release mechanism.

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

Attenuation of hypoxic current by intracellular applications of ATP regenerating agents in hippocampal CA1 neurons of rat brain slices.

PubMed

Chung, I; Zhang, Y; Eubanks, J H; Zhang, L

1998-10-01

Hypoxia-induced outward currents (hyperpolarization) were examined in hippocampal CA1 neurons of rat brain slices, using the whole-cell recording technique. Hypoxic episodes were induced by perfusing slices with an artificial cerebrospinal fluid aerated with 5% CO2/95% N2 rather than 5% CO2/95% O2, for about 3 min. The hypoxic current was consistently and reproducibly induced in CA1 neurons dialysed with an ATP-free patch pipette solution. This current manifested as an outward shift in the holding current in association with increased conductance, and it reversed at -78 +/- 2.5 mV, with a linear I-V relation in the range of -100 to -40 mV. To provide extra energy resources to individual neurons recorded, agents were added to the patch pipette solution, including MgATP alone, MgATP + phosphocreatine + creatine kinase, or MgATP + creatine. In CA1 neurons dialysed with patch solutions including these agents, hypoxia produced small outward currents in comparison with those observed in CA1 neurons dialysed with the ATP-free solution. Among the above agents examined, whole-cell dialysis with MgATP + creatine was the most effective at decreasing the hypoxic outward currents. We suggest that the hypoxic hyperpolarization is closely related to energy metabolism in individual CA1 neurons, and that the energy supply provided by phosphocreatine metabolism may play a critical role during transient metabolic stress.

Octopamine increases the excitability of neurons in the snail feeding system by modulation of inward sodium current but not outward potassium currents.

PubMed

Vehovszky, Agnes; Szabó, Henriette; Elliott, Christopher J H

2005-12-06

Although octopamine has long been known to have major roles as both transmitter and modulator in arthropods, it has only recently been shown to be functionally important in molluscs, playing a role as a neurotransmitter in the feeding network of the snail Lymnaea stagnalis. The synaptic potentials cannot explain all the effects of octopamine-containing neurons on the feeding network, and here we test the hypothesis that octopamine is also a neuromodulator. The excitability of the B1 and B4 motoneurons in the buccal ganglia to depolarising current clamp pulses is significantly (P < < 0.05) increased by (10 microM) octopamine, whereas the B2 motoneuron becomes significantly less excitable. The ionic currents evoked by voltage steps were recorded using 2-electrode voltage clamp. The outward current of B1, B2 and B4 motoneurons had two components, a transient IA current and a sustained IK delayed-rectifier current, but neither was modulated by octopamine in any of these three buccal neurons. The fast inward current was eliminated in sodium-free saline and so is likely to be carried by sodium ions. 10 microM octopamine enhanced this current by 33 and 45% in the B1 and B4 motoneurons respectively (P < < 0.05), but a small reduction was seen in the B2 neuron. A Hodgkin-Huxley style simulation of the B1 motoneuron confirms that a 33% increase in the fast inward current by octopamine increases the excitability markedly. We conclude that octopamine is also a neuromodulator in snails, changing the excitability of the buccal neurons. This is supported by the close relationship from the voltage clamp data, through the quantitative simulation, to the action potential threshold, changing the properties of neurons in a rhythmic network. The increase in inward sodium current provides an explanation for the polycyclic modulation of the feeding system by the octopamine-containing interneurons, making feeding easier to initiate and making the feeding bursts more intense.

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.

The delayed rectifier, IKI, is the major conductance in type I vestibular hair cells across vestibular end organs

NASA Technical Reports Server (NTRS)

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

1996-01-01

Hair cells were dissociated from the semicircular canal, utricle, lagena and saccule of white king pigeons. Type I hair cells were identified morphologically based on the ratios of neck width to cuticular plate width (NPR < 0.72) as well as neck width to cell body width (NBR < 0.64). The perforated patch variant of the whole-cell recording technique was used to measure electrical properties from type I hair cells. In voltage-clamp, the membrane properties of all identified type I cells were dominated by a predominantly outward potassium current, previously characterized in semicircular canal as IKI. Zero-current potential, activation, deactivation, slope conductance, pharmacologic and steady-state properties of the complex currents were not statistically different between type I hair cells of different vestibular end organs. The voltage dependence causes a significant proportion of this conductance to be active about the cell's zero-current potential. The first report of the whole-cell activation kinetics of the conductance is presented, showing a voltage dependence that could be best fit by an equation for a single exponential. Results presented here are the first data from pigeon dissociated type I hair cells from utricle, saccule and lagena suggesting that the basolateral conductances of a morphologically identified population of type I hair cells are conserved between functionally different vestibular end organs; the major conductance being a delayed rectifier characterized previously in semicircular canal hair cells as IKI.

Two modes of polyamine block regulating the cardiac inward rectifier K+ current IK1 as revealed by a study of the Kir2.1 channel expressed in a human cell line.

PubMed

Ishihara, Keiko; Ehara, Tsuguhisa

2004-04-01

The strong inward rectifier K(+) current, I(K1), shows significant outward current amplitude in the voltage range near the reversal potential and thereby causes rapid repolarization at the final phase of cardiac action potentials. However, the mechanism that generates the outward I(K1) is not well understood. We recorded currents from the inside-out patches of HEK 293T cells that express the strong inward rectifier K(+) channel Kir2.1 and studied the blockage of the currents caused by cytoplasmic polyamines, namely, spermine and spermidine. The outward current-voltage (I-V) relationships of Kir2.1, obtained with 5-10 microm spermine or 10-100 microm spermidine, were similar to the steady-state outward I-V relationship of I(K1), showing a peak at a level that is approximately 20 mV more positive than the reversal potential, with a negative slope at more positive voltages. The relationships exhibited a plateau or a double-hump shape with 1 microm spermine/spermidine or 0.1 microm spermine, respectively. In the chord conductance-voltage relationships, there were extra conductances in the positive voltage range, which could not be described by the Boltzmann relations fitting the major part of the relationships. The extra conductances, which generated most of the outward currents in the presence of 5-10 microm spermine or 10-100 microm spermidine, were quantitatively explained by a model that considered two populations of Kir2.1 channels, which were blocked by polyamines in either a high-affinity mode (Mode 1 channel) or a low-affinity mode (Mode 2 channel). Analysis of the inward tail currents following test pulses indicated that the relief from the spermine block of Kir2.1 consisted of an exponential component and a virtually instantaneous component. The fractions of the two components nearly agreed with the fractions of the blockages in Mode 1 and Mode 2 calculated by the model. The estimated proportion of Mode 1 channels to total channels was 0.9 with 0.1-10 microm spermine, 0.75 with 1-100 microm spermidine, and between 0.75 and 0.9 when spermine and spermidine coexisted. An interaction of spermine/spermidine with the channel at an intracellular site appeared to modify the equilibrium of the two conformational channel states that allow different modes of blockage. Our results suggest that the outward I(K1) is primarily generated by channels with lower affinities for polyamines. Polyamines may regulate the amplitude of the outward I(K1), not only by blocking the channels but also by modifying the proportion of channels that show different sensitivities to the polyamine block.

Route, mechanism, and implications of proton import during Na+/K+ exchange by native Na+/K+-ATPase pumps

PubMed Central

Vedovato, Natascia

2014-01-01

A single Na+/K+-ATPase pumps three Na+ outwards and two K+ inwards by alternately exposing ion-binding sites to opposite sides of the membrane in a conformational sequence coupled to pump autophosphorylation from ATP and auto-dephosphorylation. The larger flow of Na+ than K+ generates outward current across the cell membrane. Less well understood is the ability of Na+/K+ pumps to generate an inward current of protons. Originally noted in pumps deprived of external K+ and Na+ ions, as inward current at negative membrane potentials that becomes amplified when external pH is lowered, this proton current is generally viewed as an artifact of those unnatural conditions. We demonstrate here that this inward current also flows at physiological K+ and Na+ concentrations. We show that protons exploit ready reversibility of conformational changes associated with extracellular Na+ release from phosphorylated Na+/K+ pumps. Reversal of a subset of these transitions allows an extracellular proton to bind an acidic side chain and to be subsequently released to the cytoplasm. This back-step of phosphorylated Na+/K+ pumps that enables proton import is not required for completion of the 3 Na+/2 K+ transport cycle. However, the back-step occurs readily during Na+/K+ transport when external K+ ion binding and occlusion are delayed, and it occurs more frequently when lowered extracellular pH raises the probability of protonation of the externally accessible carboxylate side chain. The proton route passes through the Na+-selective binding site III and is distinct from the principal pathway traversed by the majority of transported Na+ and K+ ions that passes through binding site II. The inferred occurrence of Na+/K+ exchange and H+ import during the same conformational cycle of a single molecule identifies the Na+/K+ pump as a hybrid transporter. Whether Na+/K+ pump–mediated proton inflow may have any physiological or pathophysiological significance remains to be clarified. PMID:24688018

Characterization of constitutive and acid-induced outwardly rectifying chloride currents in immortalized mouse distal tubular cells.

PubMed

Valinsky, William C; Touyz, Rhian M; Shrier, Alvin

2017-08-01

Thiazides block Na + reabsorption while enhancing Ca 2+ reabsorption in the kidney. As previously demonstrated in immortalized mouse distal convoluted tubule (MDCT) cells, chlorothiazide application induced a robust plasma membrane hyperpolarization, which increased Ca 2+ uptake. This essential thiazide-induced hyperpolarization was prevented by the Cl - channel inhibitor 5-Nitro-2-(3-phenylpropylamino) benzoic acid (NPPB), implicating NPPB-sensitive Cl - channels, however the nature of these Cl - channels has been rarely described in the literature. Here we show that MDCT cells express a dominant, outwardly rectifying Cl - current at extracellular pH7.4. This constitutive Cl - current was more permeable to larger anions (Eisenman sequence I; I - >Br - ≥Cl - ) and was substantially inhibited by >100mM [Ca 2+ ] o , which distinguished it from ClC-K2/barttin. Moreover, the constitutive Cl - current was blocked by NPPB, along with other Cl - channel inhibitors (4,4'-diisothiocyanatostilbene-2,2'-disulfonate, DIDS; flufenamic acid, FFA). Subjecting the MDCT cells to an acidic extracellular solution (pH<5.5) induced a substantially larger outwardly rectifying NPPB-sensitive Cl - current. This acid-induced Cl - current was also anion permeable (I - >Br - >Cl - ), but was distinguished from the constitutive Cl - current by its rectification characteristics, ion sensitivities, and response to FFA. In addition, we have identified similar outwardly rectifying and acid-sensitive currents in immortalized cells from the inner medullary collecting duct (mIMCD-3 cells). Expression of an acid-induced Cl - current would be particularly relevant in the acidic IMCD (pH<5.5). To our knowledge, the properties of these Cl - currents are unique and provide the mechanisms to account for the Cl - efflux previously speculated to be present in MDCT cells. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Preservation of cardiac function by prolonged action potentials in mice deficient of KChIP2.

PubMed

Grubb, Søren; Aistrup, Gary L; Koivumäki, Jussi T; Speerschneider, Tobias; Gottlieb, Lisa A; Mutsaers, Nancy A M; Olesen, Søren-Peter; Calloe, Kirstine; Thomsen, Morten B

2015-08-01

Inherited ion channelopathies and electrical remodeling in heart disease alter the cardiac action potential with important consequences for excitation-contraction coupling. Potassium channel-interacting protein 2 (KChIP2) is reduced in heart failure and interacts under physiological conditions with both Kv4 to conduct the fast-recovering transient outward K(+) current (Ito,f) and with CaV1.2 to mediate the inward L-type Ca(2+) current (ICa,L). Anesthetized KChIP2(-/-) mice have normal cardiac contraction despite the lower ICa,L, and we hypothesized that the delayed repolarization could contribute to the preservation of contractile function. Detailed analysis of current kinetics shows that only ICa,L density is reduced, and immunoblots demonstrate unaltered CaV1.2 and CaVβ₂ protein levels. Computer modeling suggests that delayed repolarization would prolong the period of Ca(2+) entry into the cell, thereby augmenting Ca(2+)-induced Ca(2+) release. Ca(2+) transients in disaggregated KChIP2(-/-) cardiomyocytes are indeed comparable to wild-type transients, corroborating the preserved contractile function and suggesting that the compensatory mechanism lies in the Ca(2+)-induced Ca(2+) release event. We next functionally probed dyad structure, ryanodine receptor Ca(2+) sensitivity, and sarcoplasmic reticulum Ca(2+) load and found that increased temporal synchronicity of the Ca(2+) release in KChIP2(-/-) cardiomyocytes may reflect improved dyad structure aiding the compensatory mechanisms in preserving cardiac contractile force. Thus the bimodal effect of KChIP2 on Ito,f and ICa,L constitutes an important regulatory effect of KChIP2 on cardiac contractility, and we conclude that delayed repolarization and improved dyad structure function together to preserve cardiac contraction in KChIP2(-/-) mice. Copyright © 2015 the American Physiological Society.

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.

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

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.

Two modes of polyamine block regulating the cardiac inward rectifier K+ current IK1 as revealed by a study of the Kir2.1 channel expressed in a human cell line

PubMed Central

Ishihara, Keiko; Ehara, Tsuguhisa

2004-01-01

The strong inward rectifier K+ current, IK1, shows significant outward current amplitude in the voltage range near the reversal potential and thereby causes rapid repolarization at the final phase of cardiac action potentials. However, the mechanism that generates the outward IK1 is not well understood. We recorded currents from the inside-out patches of HEK 293T cells that express the strong inward rectifier K+ channel Kir2.1 and studied the blockage of the currents caused by cytoplasmic polyamines, namely, spermine and spermidine. The outward current–voltage (I–V) relationships of Kir2.1, obtained with 5–10μm spermine or 10–100μm spermidine, were similar to the steady-state outward I–V relationship of IK1, showing a peak at a level that is ∼20mV more positive than the reversal potential, with a negative slope at more positive voltages. The relationships exhibited a plateau or a double-hump shape with 1μm spermine/spermidine or 0.1μm spermine, respectively. In the chord conductance–voltage relationships, there were extra conductances in the positive voltage range, which could not be described by the Boltzmann relations fitting the major part of the relationships. The extra conductances, which generated most of the outward currents in the presence of 5–10μm spermine or 10–100μm spermidine, were quantitatively explained by a model that considered two populations of Kir2.1 channels, which were blocked by polyamines in either a high-affinity mode (Mode 1 channel) or a low-affinity mode (Mode 2 channel). Analysis of the inward tail currents following test pulses indicated that the relief from the spermine block of Kir2.1 consisted of an exponential component and a virtually instantaneous component. The fractions of the two components nearly agreed with the fractions of the blockages in Mode 1 and Mode 2 calculated by the model. The estimated proportion of Mode 1 channels to total channels was 0.9 with 0.1–10μm spermine, 0.75 with 1–100μm spermidine, and between 0.75 and 0.9 when spermine and spermidine coexisted. An interaction of spermine/spermidine with the channel at an intracellular site appeared to modify the equilibrium of the two conformational channel states that allow different modes of blockage. Our results suggest that the outward IK1 is primarily generated by channels with lower affinities for polyamines. Polyamines may regulate the amplitude of the outward IK1, not only by blocking the channels but also by modifying the proportion of channels that show different sensitivities to the polyamine block. PMID:14724206

Delayed rectifier potassium channels are involved in SO2 derivative-induced hippocampal neuronal injury.

PubMed

Li, Guangke; Sang, Nan

2009-01-01

Recent studies implicate the possible neurotoxicity of SO(2), however, its mechanisms remain unclear. In the present study, we investigated SO(2) derivative-induced effect on delayed rectifier potassium channels (I(K)) and cellular death/apoptosis in primary cultured hippocampal neurons. The results demonstrate that SO(2) derivatives (NaHSO(3) and Na(2)SO(3), 3:1M/M) effectively augmented I(K) and promoted the activation of delayed rectifier potassium channels. Also, SO(2) derivatives increased neuronal death percentage and contributed to the formation of DNA ladder in concentration-dependent manners. Interestingly, the neuronal death and DNA ladder formation, caused by SO(2) derivatives, could be attenuated by the delayed rectifier potassium channel blocker (tetraethylammonium, TEA), but not by the transient outward potassium channel blocker (4-aminopyridine, 4-AP). It implies that stimulating delayed rectifier potassium channels were involved in SO(2) derivative-caused hippocampal neuronal insults, and blocking these channels might be one of the possibly clinical treatment for SO(2)-caused neuronal dysfunction.

Outwardly Propagating Flames at Elevated Pressures

NASA Technical Reports Server (NTRS)

Law, C. K.; Rozenchan, G.; Tse, S. D.; Zhu, D. L.

2001-01-01

Spherical, outwardly-propagating flames of CH4-O2-inert and H2-O2-inert mixtures were experimentally studied in a high pressure apparatus. Stretch-free flame speeds and Markstein lengths were extracted for a wide range of pressures and equivalence ratios for spherically-symmetric, smooth flamefronts and compared to numerical computations with detailed chemistry and transport, as well as existing data in the literature. Wrinkle development was examined for propagating flames that were unstable under our experimental conditions. Hydrodynamic cells developed for most H2-air and CH4-air flames at elevated pressures, while thermal-diffusive instabilities were also observed for lean and near-stoichiometric hydrogen flames at pressures above atmospheric. Strategies in suppressing or delaying the onset of cell formation have been assessed. Buoyancy effects affected sufficiently off-stoichiometric CH4 mixtures at high pressures.

Electrophysiological and mechanical effects of caffeic acid phenethyl ester, a novel cardioprotective agent with antiarrhythmic activity, in guinea-pig heart.

PubMed

Chang, Gwo-Jyh; Chang, Chi-Jen; Chen, Wei-Jan; Yeh, Yung-Hsin; Lee, Hsiao-Yu

2013-02-28

Caffeic acid phenethyl ester (CAPE) is an active component of propolis that exhibits cardioprotective and antiarrhythmic effects. The detailed mechanisms underlying these effects, however, are not entirely understood. The aim of this study was to elucidate the electromechanical effects of CAPE in guinea-pig cardiac preparations. Intracardiac electrograms, left ventricular (LV) pressure, and the anti-arrhythmic efficacy were determined using isolated hearts. Action potentials of papillary muscles were assessed with microelectrodes, Ca(2+) transients were measured by fluorescence, and ion fluxes were measured by patch-clamp techniques. In a perfused heart model, CAPE prolonged the atrio-ventricular conduction interval, the Wenckebach cycle length, and the refractory periods of the AV node and His-Purkinje system, while shortening the QT interval. CAPE reduced the occurrence of reperfusion-induced ventricular fibrillation and decreased LV pressure in isolated hearts. In papillary muscles, CAPE shortened the action potential duration and reduced both the maximum upstroke velocity and contractile force. In fura-2-loaded single ventricular myocytes, CAPE decreased cell shortening and the Ca(2+) transient amplitude. Patch-clamp experiments revealed that CAPE produced a use-dependent decrease in L-type Ca(2+) current (ICa,L) (IC50=1.1 μM) and Na(+) current (INa) (IC50=0.43 μM), caused a negative-shift of the voltage-dependent inactivation and a delay of recovery from inactivation. CAPE decreased the delayed outward K(+) current (IK) slightly, without affecting the inward rectifier K(+) current (IK1). These results suggest that the preferential inhibition of Ca(2+) inward and Na(+) inward currents by CAPE may induce major electromechanical alterations in guinea-pig cardiac preparations, which may underlie its antiarrhythmic action. Copyright © 2013 Elsevier B.V. All rights reserved.

THE EFFECTS OF CURRENT FLOW ON BIOELECTRIC POTENTIAL

PubMed Central

Blinks, L. R.

1936-01-01

String galvanometer records show the effect of current flow upon the bioelectric potential of Nitella cells. Three classes of effects are distinguished. 1. Counter E.M.F'S, due either to static or polarization capacity, probably the latter. These account for the high effective resistance of the cells. They record as symmetrical charge and discharge curves, which are similar for currents passing inward or outward across the protoplasm, and increase in magnitude with increasing current density. The normal positive bioelectric potential may be increased by inward currents some 100 or 200 mv., or to a total of 300 to 400 mv. The regular decrease with outward current flow is much less (40 to 50 mv.) since larger outward currents produce the next characteristic effect. 2. Stimulation. This occurs with outward currents of a density which varies somewhat from cell to cell, but is often between 1 and 2 µa/cm.2 of cell surface. At this threshold a regular counter E.M.F. starts to develop but passes over with an inflection into a rapid decrease or even disappearance of positive P.D., in a sigmoid curve with a cusp near its apex. If the current is stopped early in the curve regular depolarization occurs, but if continued a little longer beyond the first inflection, stimulation goes on to completion even though the current is then stopped. This is the "action current" or negative variation which is self propagated down the cell. During the most profound depression of P.D. in stimulation, current flow produces little or no counter E.M.F., the resistance of the cell being purely ohmic and very low. Then as the P.D. begins to recover, after a second or two, counter E.M.F. also reappears, both becoming nearly normal in 10 or 15 seconds. The threshold for further stimulation remains enhanced for some time, successively larger current densities being needed to stimulate after each action current. The recovery process is also powerful enough to occur even though the original stimulating outward current continues to flow during the entire negative variation; recovery is slightly slower in this case however. Stimulation may be produced at the break of large inward currents, doubtless by discharge of the enhanced positive P.D. (polarization). 3. Restorative Effects.—The flow of inward current during a negative variation somewhat speeds up recovery. This effect is still more strikingly shown in cells exposed to KCl solutions, which may be regarded as causing "permanent stimulation" by inhibiting recovery from a negative variation. Small currents in either direction now produce no counter E.M.F., so that the effective resistance of the cells is very low. With inward currents at a threshold density of some 10 to 20 µa/cm.2, however, there is a counter E.M.F. produced, which builds up in a sigmoid curve to some 100 to 200 mv. positive P.D. This usually shows a marked cusp and then fluctuates irregularly during current flow, falling off abruptly when the current is stopped. Further increases of current density produce this P.D. more rapidly, while decreased densities again cease to be effective below a certain threshold. The effects in Nitella are compared with those in Valonia and Halicystis, which display many of the same phenomena under proper conditions. It is suggested that the regular counter E.M.F.'S (polarizations) are due to the presence of an intact surface film or other structure offering differential hindrance to ionic passage. Small currents do not affect this structure, but it is possibly altered or destroyed by large outward currents, restored by large inward currents. Mechanisms which might accomplish the destruction and restoration are discussed. These include changes of acidity by differential migration of H ion (membrane "electrolysis"); movement of inorganic ions such as potassium; movement of organic ions, (such as Osterhout's substance R), or the radicals (such as fatty acid) of the surface film itself. Although no decision can be yet made between these, much evidence indicates that inward currents increase acidity in some critical part of the protoplasm, while outward ones decrease acidity. PMID:19872991

Transient outward currents and changes of their gating properties after cell activation in thrombocytes of the newt.

PubMed Central

Kawa, K

1987-01-01

1. The electrical properties of the cell membrane of thrombocytes in the newt, Triturus pyrrhogaster, were studied using the whole-cell variation of the patch-electrode voltage-clamp technique. 2. In medium containing Ca2+ (1.8 mM), activated thrombocytes became round and then spread on the glass. Activation of thrombocytes was inhibited by the removal of external Ca2+ and addition of 1 w/v% albumin to the external media. 3. For thrombocytes kept in the resting state, depolarizations more positive than -30 mV evoked transient outward currents which decayed completely during the duration of the depolarization (150 ms). The half-decay time of the currents became smaller as the depolarizing pulse strengthened, reaching about 20 ms at +30 mV (20 degrees C). 4. The outward currents are identified as K+ currents, since (1) their reversal potential depended on extracellular K+ concentration and (2) the outward currents were suppressed either by external application of 4-aminopyridine (1 mM) or by internal application of Cs+ (120 mM). The monovalent cation selectivities of the K+ channels were evaluated from the reversal potential as Tl (1.68) greater than K(1.0) greater than Rb (0.89) greater than NH4 (0.13) greater than Na(less than 0.03). 5. When the thrombocytes had been activated, depolarization again evoked K+ currents. The currents, however, showed negligible or small decay during the duration of the depolarization (150 ms). The rate of recovery from preceding depolarization was also reduced to about one-sixth. 6. The sensitivity to 4-aminopyridine and the selectivity of the K+ channels were not changed by cell activation. 7. We conclude that during activation of thrombocytes the inactivation of the K+ channels is almost eliminated. Removal of inactivation of the K+ channels was also induced in resting thrombocytes by intracellular application of 4-bromoacetamide (50 microM). PMID:2443665

Selectivity of externally facing ion-binding sites in the Na/K pump to alkali metals and organic cations

PubMed Central

Ratheal, Ian M.; Virgin, Gail K.; Yu, Haibo; Roux, Benoît; Gatto, Craig; Artigas, Pablo

2010-01-01

The Na/K pump is a P-type ATPase that exchanges three intracellular Na+ ions for two extracellular K+ ions through the plasmalemma of nearly all animal cells. The mechanisms involved in cation selection by the pump's ion-binding sites (site I and site II bind either Na+ or K+; site III binds only Na+) are poorly understood. We studied cation selectivity by outward-facing sites (high K+ affinity) of Na/K pumps expressed in Xenopus oocytes, under voltage clamp. Guanidinium+, methylguanidinium+, and aminoguanidinium+ produced two phenomena possibly reflecting actions at site III: (i) voltage-dependent inhibition (VDI) of outwardly directed pump current at saturating K+, and (ii) induction of pump-mediated, guanidinium-derivative–carried inward current at negative potentials without Na+ and K+. In contrast, formamidinium+ and acetamidinium+ induced K+-like outward currents. Measurement of ouabain-sensitive ATPase activity and radiolabeled cation uptake confirmed that these cations are external K+ congeners. Molecular dynamics simulations indicate that bound organic cations induce minor distortion of the binding sites. Among tested metals, only Li+ induced Na+-like VDI, whereas all metals tested except Na+ induced K+-like outward currents. Pump-mediated K+-like organic cation transport challenges the concept of rigid structural models in which ion specificity at site I and site II arises from a precise and unique arrangement of coordinating ligands. Furthermore, actions by guanidinium+ derivatives suggest that Na+ binds to site III in a hydrated form and that the inward current observed without external Na+ and K+ represents cation transport when normal occlusion at sites I and II is impaired. These results provide insights on external ion selectivity at the three binding sites. PMID:20937860

PLC-dependent intracellular Ca2+ release was associated with C6-ceramide-induced inhibition of Na+ current in rat granule cells.

PubMed

Liu, Zheng; Fei, Xiao-Wei; Fang, Yan-Jia; Shi, Wen-Jie; Zhang, Yu-Qiu; Mei, Yan-Ai

2008-09-01

In this report, the effects of C(6)-ceramide on the voltage-gated inward Na(+) currents (I(Na)), two types of main K(+) current [outward rectifier delayed K(+) current (I(K)) and outward transient K(+) current (I(A))], and cell death in cultured rat cerebellar granule cells were investigated. At concentrations of 0.01-100 microM, ceramide produced a dose-dependent and reversible inhibition of I(Na) without alteration of the steady-state activation and inactivation properties. Treatment with C(2)-ceramide caused a similar inhibitory effect on I(Na). However, dihydro-C(6)-ceramide failed to modulate I(Na). The effect of C(6)-ceramide on I(Na) was abolished by intracellular infusion of the Ca(2+)-chelating agent, 1,2-bis (2-aminophenoxy) ethane-N, N, N9, N9-tetraacetic acid, but was mimicked by application of caffeine. Blocking the release of Ca(2+) from the sarcoplasmic reticulum with ryanodine receptor blocker induced a gradual increase in I(Na) amplitude and eliminated the effect of ceramide on I(Na). In contrast, the blocker of the inositol 1,4,5-trisphosphate-sensitive Ca(2+) receptor did not affect the action of C(6)-ceramide. Intracellular application of GTPgammaS also induced a gradual decrease in I(Na) amplitude, while GDPbetaS eliminated the effect of C(6)-ceramide on I(Na). Furthermore, the C(6)-ceramide effect on I(Na) was abolished after application of the phospholipase C (PLC) blockers and was greatly reduced by the calmodulin inhibitors. Fluorescence staining showed that C(6)-ceramide decreased cell viability and blocking I(Na) by tetrodotoxin did not mimic the effect of C(6)-ceramide, and inhibiting intracellular Ca(2+) release by dantrolene could not decrease the C(6)-ceramide-induced cell death. We therefore suggest that increased PLC-dependent Ca(2+) release through the ryanodine-sensitive Ca(2+) receptor may be responsible for the C(6)-ceramide-induced inhibition of I(Na), which does not seem to be associated with C(6)-ceramide-induced granule neuron death.

Synchronization modulation of Na/K pumps on Xenopus oocytes

NASA Astrophysics Data System (ADS)

Liang, Pengfei; Mast, Jason; Chen, Wei

We developed a new technique named synchronization modulation to electrically synchronize and modulate the Na/K pump molecules by a specially designed oscillating electric field. This technique is based on the theory of energy-trap in quantum physics as well as the concept of electronic synchrotron accelerator. As a result, the Na-transports are all entrapped into the positive half-cycle of the applied electric field and consequently, all of the K-transports are entrapped into the negative half cycle of the field. To demonstrate the process of the pump synchronization and modulation, we use Xenopus oocytes as a platform and introduce two-electrode whole-cell voltage clamp in measurement of pump current. Practically, we first synchronize the pump molecules running at the same pace (rate and phase) by a specially designed oscillation electric field. Then, we carefully maintain the pump synchronization status and gradually change the field frequency (decrease and increase) to modulate the pump molecules to newer pumping rate. The result shows a separation of the inward K current from the outward Na current, and about 10 time increase of the total (inward plus outward) pump current from the net outward current from the random paced pump molecules. Also, the ratio of the modulated total pump current with synchronized total pump current is consistent with the ratio of their field frequencies.

Delayed Repolarization Underlies Ventricular Arrhythmias in Rats With Heart Failure and Preserved Ejection Fraction.

PubMed

Cho, Jae Hyung; Zhang, Rui; Kilfoil, Peter J; Gallet, Romain; de Couto, Geoffrey; Bresee, Catherine; Goldhaber, Joshua I; Marbán, Eduardo; Cingolani, Eugenio

2017-11-21

Heart failure with preserved ejection fraction (HFpEF) represents approximately half of heart failure, and its incidence continues to increase. The leading cause of mortality in HFpEF is sudden death, but little is known about the underlying mechanisms. Dahl salt-sensitive rats were fed a high-salt diet (8% NaCl) from 7 weeks of age to induce HFpEF (n=38). Rats fed a normal-salt diet (0.3% NaCl) served as controls (n=13). Echocardiograms were performed to assess systolic and diastolic function from 14 weeks of age. HFpEF-verified and control rats underwent programmed electrical stimulation. Corrected QT interval was measured by surface ECG. The mechanisms of ventricular arrhythmias (VA) were probed by optical mapping, whole-cell patch clamp to measure action potential duration and ionic currents, and quantitative polymerase chain reaction and Western blotting to investigate changes in ion channel expression. After 7 weeks of a high-salt diet, 31 of 38 rats showed diastolic dysfunction and preserved ejection fraction along with signs of heart failure and hence were diagnosed with HFpEF. Programmed electric stimulation demonstrated increased susceptibility to VA in HFpEF rats ( P <0.001 versus controls). The arrhythmogenicity index was increased ( P <0.001) and the corrected QT interval on ECG was prolonged ( P <0.001) in HFpEF rats. Optical mapping of HFpEF hearts demonstrated prolonged action potentials ( P <0.05) and multiple reentry circuits during induced VA. Single-cell recordings of cardiomyocytes isolated from HFpEF rats confirmed a delay of repolarization ( P =0.001) and revealed downregulation of transient outward potassium current ( I to ; P <0.05). The rapid components of the delayed rectifier potassium current ( I Kr ) and the inward rectifier potassium current ( I K1 ) were also downregulated ( P <0.05), but the current densities were much lower than for I to . In accordance with the reduction of I to , both Kcnd3 transcript and Kv4.3 protein levels were decreased in HFpEF rat hearts. Susceptibility to VA was markedly increased in rats with HFpEF. Underlying abnormalities include QT prolongation, delayed repolarization from downregulation of potassium currents, and multiple reentry circuits during VA. Our findings are consistent with the hypothesis that potassium current downregulation leads to abnormal repolarization in HFpEF, which in turn predisposes to VA and sudden cardiac death. © 2017 American Heart Association, Inc.

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.

SLO-2 potassium channel is an important regulator of neurotransmitter release in Caenorhabditis elegans

PubMed Central

Liu, Ping; Chen, Bojun; Wang, Zhao-Wen

2014-01-01

Slo2 channels are prominent K+ channels in mammalian neurons but their physiological functions are not well understood. Here we investigate physiological functions and regulation of the C. elegans homologue SLO-2 in motor neurons through electrophysiological analyses of wild-type and mutant worms. We find that SLO-2 is the primary K+ channel conducting delayed outward current in cholinergic motor neurons, and one of two K+ channels with this function in GABAergic motor neurons. Loss-of-function mutation of slo-2 increases the duration and charge transfer rate of spontaneous postsynaptic current bursts at the neuromuscular junction, which are physiological signals used by motor neurons to control muscle cells, without altering postsynaptic receptor sensitivity. SLO-2 activity in motor neurons depends on Ca2+ entry through EGL-19, an L-type voltage-gated Ca2+ channel (CaV1), but not on other proteins implicated in either Ca2+ entry or intracellular Ca2+ release. Thus, SLO-2 is functionally coupled with CaV1 and regulates neurotransmitter release. PMID:25300429

Caffeine depression of spontaneous activity in rabbit sino-atrial node cells.

PubMed

Satoh, H

1993-05-01

1. Effects of caffeine on the action potentials and the membrane currents in spontaneously beating rabbit sino-atrial (SA) node cells were examined using a two-microelectrode technique. 2. Cumulative administrations of caffeine (1-10 mM) caused a negative chronotropic effect in a concentration-dependent manner, which was not modified by atropine (0.1 microM). At 10 mM, caffeine increased the amplitude and prolonged the duration of action potentials significantly; the other parameters were unaffected. 3. In 3 of 16 preparations, caffeine (5 mM) elicited arrhythmia. At high Ca2+ (8.1 mM), caffeine (5 mM) increased the incidence of arrhythmia. 4. Caffeine (0.5-10 mM) enhanced the slow inward current, but at 10 mM decreased the enhanced peak current by 5 mM. The hyperpolarization-activated inward current was also enhanced by caffeine, but 10 mM caffeine decreased the current peak as compared with that at 5 mM. In addition, caffeine inhibited the delayed rectifying outward current in a concentration-dependent manner, accompanied by a depressed activation curve without any shift in the half-maximum activation voltage. 5. Caffeine elevated the cytoplasmic Ca2+ level in the SA node cells loaded with Ca(2+)-sensitive fluorescent dye (fura-2). 6. These results suggest that caffeine enhances and/or inhibits the ionic currents and elicits arrhythmia due to the induction of cellular calcium overload.

Properties of the cromakalim-induced potassium conductance in smooth muscle cells isolated from the rabbit portal vein.

PubMed Central

Beech, D. J.; Bolton, T. B.

1989-01-01

1. Single smooth muscle cells were isolated freshly from the rabbit portal vein and membrane currents were recorded by the whole-cell or excised patch configurations of the patch-clamp technique at room temperature. 2. Cromakalim (Ckm, 10 microM) induced a potassium current (ICkm) that showed no pronounced voltage-dependence and had low current noise. 3. This current, ICkm, was inhibited by (in order of potency): phencyclidine greater than quinidine greater than 4-aminopyridine greater than tetraethylammonium ions (TEA). These drugs inhibited the delayed rectifier current, IdK, which is activated by depolarization of the cell, with the same order of potency. 4. Large conductance calcium-activated potassium channels (LKCa) in isolated membrane patches were blocked by (in order of potency) quinidine greater than TEA approximately phencyclidine. 4-Aminopyridine was ineffective. A similar order of potency was found for block of spontaneous transient outward currents thought to represent bursts of openings of LKCa channels. 5. The low current noise of ICkm at positive potentials, and its susceptibility to inhibitors indicated that it was not carried by LKCa channels, and that it may be carried by channels which underlie IdK. It was observed that when ICkm was activated, IdK was reduced. However, in two experiments, ICkm was much more susceptible to glibenclamide than IdK; possible reasons for this are discussed. PMID:2590772

Sensitivity of Rabbit Ventricular Action Potential and Ca2+ Dynamics to Small Variations in Membrane Currents and Ion Diffusion Coefficients

PubMed Central

Lo, Yuan Hung; Peachey, Tom; Abramson, David; McCulloch, Andrew

2013-01-01

Little is known about how small variations in ionic currents and Ca2+ and Na+ diffusion coefficients impact action potential and Ca2+ dynamics in rabbit ventricular myocytes. We applied sensitivity analysis to quantify the sensitivity of Shannon et al. model (Biophys. J., 2004) to 5%–10% changes in currents conductance, channels distribution, and ion diffusion in rabbit ventricular cells. We found that action potential duration and Ca2+ peaks are highly sensitive to 10% increase in L-type Ca2+ current; moderately influenced by 10% increase in Na+-Ca2+ exchanger, Na+-K+ pump, rapid delayed and slow transient outward K+ currents, and Cl− background current; insensitive to 10% increases in all other ionic currents and sarcoplasmic reticulum Ca2+ fluxes. Cell electrical activity is strongly affected by 5% shift of L-type Ca2+ channels and Na+-Ca2+ exchanger in between junctional and submembrane spaces while Ca2+-activated Cl−-channel redistribution has the modest effect. Small changes in submembrane and cytosolic diffusion coefficients for Ca2+, but not in Na+ transfer, may alter notably myocyte contraction. Our studies highlight the need for more precise measurements and further extending and testing of the Shannon et al. model. Our results demonstrate usefulness of sensitivity analysis to identify specific knowledge gaps and controversies related to ventricular cell electrophysiology and Ca2+ signaling. PMID:24222910

BmP02 Atypically Delays Kv4.2 Inactivation: Implication for a Unique Interaction between Scorpion Toxin and Potassium Channel

PubMed Central

Wu, Bin; Zhu, Yan; Shi, Jian; Tao, Jie; Ji, Yonghua

2016-01-01

BmP02, a short-chain peptide with 28 residues from the venom of Chinese scorpion Buthus martensi Karsch, has been reported to inhibit the transient outward potassium currents (Ito) in rat ventricular muscle cells. However, it remains unclear whether BmP02 modulates the Kv4.2 channel, one of the main contributors to Ito. The present study investigated the effects of BmP02 on Kv4.2 kinetics and its underlying molecular mechanism. The electrophysiological recordings showed that the inactivation of Kv4.2 expressed in HEK293T cells was significantly delayed by BmP02 in a dose-response manner with EC50 of ~850 nM while the peak current, activation and voltage-dependent inactivation of Kv4.2 were not affected. Meanwhile, the recovery from inactivation of Kv4.2 was accelerated and the deactivation was slowed after the application of BmP02. The site-directed mutagenesis combined with computational modelling identified that K347 and K353, located in the turret motif of the Kv4.2, and E4/E5, D20/D21 in BmP02 are key residues to interact with BmP02 through electrostatic force. These findings not only reveal a novel interaction between Kv4.2 channel and its peptidyl modulator, but also provide valuable information for design of highly-selective Kv4.2 modulators. PMID:27690098

Outward current produced by somatostatin (SRIF) in rat anterior cingulate pyramidal cells in vitro

PubMed Central

Hicks, G A; Feniuk, W; Humphrey, P P A

1998-01-01

A high density of receptors for somatostatin (SRIF) exists in the anterior cingulate cortex but their function is unknown. Whole-cell patch clamp recordings were made from visualized deep layer pyramidal cells of the rat anterior cingulate cortex contained in isolated brain slices to investigate the putative effects of SRIF and to identify the receptor subtype(s) involved.SRIF (1–1000 nM) produced a concentration-dependent outward current which was associated with an increased membrane conductance, was sensitive to Ba2+ (300 μM–1 mM), and was absent in the presence of a maximal concentration of the GABAB receptor agonist, baclofen (100 μM). These observations suggest the outward current was carried by K+ ions.SRIF analogues also elicited outward currents with a rank potency order of (EC50, nM): octreotide (1.8)>BIM-23027 (3.7)>SRIF (20)=L-362,855 (20). BIM-23056 was without agonist or antagonist activity. Responses to L-362,855 were unlike those to the other agonists since they were sustained for the duration of the application.The sst2 receptor antagonist, L-Tyr8Cyanamid 154806 (1 μM), had no effect alone but partially reversed responses to submaximal concentrations of SRIF (100 nM, 44±6% reversal) and L-362,855 (100 nM, 70±6% reversal) and fully reversed the response to BIM-23027 (10 nM). In contrast, L-Tyr8Cyanamid 154806 did not antagonize the response to baclofen (10 μM).We conclude that SRIF activates a K+ conductance in anterior cingulate pyramidal neurones via an action predominantly at sst2 receptors. PMID:9630367

Hyperpolarizing muscarinic responses of freshly dissociated rat hippocampal CA1 neurones.

PubMed Central

Wakamori, M; Hidaka, H; Akaike, N

1993-01-01

1. Intracellular mechanisms of the muscarinic acetylcholine (ACh) response were investigated in pyramidal neurones freshly dissociated from the rat hippocampal CA1 region. Current recordings were made in the whole-cell mode using the nystatin 'perforated'-patch technique, by which the muscarinic ACh response can be continuously recorded without so-called 'run-down' phenomenon. The amount of intracellular free Ca2+ ([Ca2+]i) was fluorometrically measured using fura-2. 2. In current clamp conditions, ACh induced a transient hyperpolarization accompanied by a decrease in membrane input resistance. 3. Under voltage clamp conditions at a holding potential (Vh) of -40 mV, ACh induced two types of muscarinic currents observed either alone or together: a transient outward current and a slowly activating sustained inward current. 4. The ACh-induced transient outward current reversed the direction at K+ equilibrium potential (EK), and the reversal potential (EACh) shifted 56.7 mV for a tenfold change of extracellular K+ concentration ([K+]o). 5. The ACh-induced transient outward current increased in a sigmoidal fashion with increase in ACh concentration, where the half-maximal concentration (EC50) and the Hill coefficient (n) were 8 x 10(-7) M and 1.9, respectively. Both muscarine and carbamylcholine mimicked the ACh response, but neither McN-A-343 (M1 agonist) nor oxotremorine (cardiac M2 agonist) induced any current. 6. Muscarinic antagonists reversibly blocked the ACh response in a concentration-dependent manner. The inhibitory potency was in the order of atropine > pirenzepine > AF-DX-116. 7. The ACh-induced transient outward current was never recorded when [Ca2+]i was chelated by the acetoxymethyl ester form of 1,2-bis(O-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA AM). On the other hand, in Ca(2+)-free external solution containing 2 mM EGTA and 10 mM Mg2+, the ACh response was elicited by the first application and successive ACh applications did not induce any response. Fura-2 imaging showed that [Ca2+]i was increased when ACh was added to the external medium with or without Ca2+, though in Ca(2+)-free medium only the first application of ACh increased the [Ca2+]i. 8. The ACh response was not affected by pretreatment with pertussis toxin (PTX) but the inhibitory effect of ACh on the high-threshold Ca2+ channel was abolished completely. 9. Pretreatment with Li+ enhanced the amplitude of the transient outward current and the increase in [Ca2+]i induced by ACh. 10. The calmodulin antagonists W-7, chlorpromazine and trifluoperazine reversibly inhibited the ACh response in a concentration-dependent manner.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:7504109

Departure from corotation of the Io plasma torus - Local plasma production

NASA Technical Reports Server (NTRS)

Pontius, D. H., Jr.; Hill, T. W.

1982-01-01

The departure of the Jovian magnetosphere from rigid corotation is adequately explained by outward plasma transport at distances where L is greater than approximately 10. The departure of 5% observed in the Io plasma torus, however, is too large to be accounted for simply by plasma transport. Local plasma production is proposed as the main factor determining the corotation lag in the torus. The outward pick-up current provided by ionization of neutral atoms is calculated and related to the current produced in the ionosphere by the corotation lag. This leads to an expression giving the corotation lag of the torus as a function of radial distance. Charge transfer is found to be an important process, allowing the majority of the torus mass to be ejected from the magnetosphere in a neutral state. Thus, the mass loading rate is found to be several times that inferred from examination of the corotation lag associated with outward plasma transport.

Prolonged action potential duration in cardiac ablation of PDK1 mice.

PubMed

Han, Zhonglin; Jiang, Yu; Yang, Zhongzhou; Cao, Kejiang; Wang, Dao W

2015-01-01

The involvement of the AGC protein kinase family in regulating arrhythmia has drawn considerable attention, but the underlying mechanisms are still not clear. The aim of this study is to explore the role of 3-phosphoinositide-dependent protein kinase-1 (PDK1), one of upstream protein kinases of the AGC protein kinase family, in the pathogenesis of dysregulated electrophysiological basis. PDK1(F/F) αMHC-Cre mice and PDK1(F/F) mice were divided into experiment group and control group. Using patch clamping technology, we explored action potential duration in both groups, and investigated the functions of transient outward potassium channel and L-type Ca(2+) channel to explain the abnormal action potential duration. Significant prolongation action potential duration was found in mice with PDK1 deletion. Further, the peak current of transient outward potassium current and L-type Ca(2+) current were decreased by 84% and 49% respectively. In addition, dysregulation of channel kinetics lead to action potential duration prolongation further. In conclusion, we have demonstrated that PDK1 participates in action potential prolongation in cardiac ablation of PDK1 mice. This effect is likely to be mediated largely through downregulation of transient outward potassium current. These findings indicate the modulation of the PDK1 pathway could provide a new mechanism for abnormal electrophysiological basis.

Nonselective Currents and Channels in Plasma Membranes of Protoplasts from Coats of Developing Seeds of Bean1

PubMed Central

Zhang, Wen-Hao; Skerrett, Martha; Walker, N. Alan; Patrick, John W.; Tyerman, Stephen D.

2002-01-01

In developing bean (Phaseolus vulgaris) seeds, phloem-imported nutrients move in the symplast from sieve elements to the ground parenchyma cells where they are transported across the plasma membrane into the seed apoplast. To study the mechanisms underlying this transport, channel currents in ground parenchyma protoplasts were characterized using patch clamp. A fast-activating outward current was found in all protoplasts, whereas a slowly activating outward current was observed in approximately 25% of protoplasts. The two currents had low selectivity for univalent cations, but the slow current was more selective for K+ over Cl− (PK:PCl = 3.6–4.2) than the fast current (PK:PCl = 1.8–2.5) and also displayed Ca2+ selectivity. The slow current was blocked by Ba2+, whereas both currents were blocked by Gd3+ and La3+. Efflux of K+ from seed coat halves was inhibited 25% by Gd3+ and La3+ but was stimulated by Ba2+ and Cs+, suggesting that only the fast current may be a component in the pathway for K+ release. An “instantaneous” inward current observed in all protoplasts exhibited similar pharmacology and permeability for univalent cations to the fast outward current. In outside-out patches, two classes of depolarization-activated cation-selective channels were observed: one slowly activating of low conductance (determined from nonstationary noise to be 2.4 pS) and another with conductances 10-fold higher. Both channels occurred at high density. The higher conductance channel in 10 mm KCl had PK:PCl = 2.8. Such nonselective channels in the seed coat ground parenchyma cell could function to allow some of the efflux of phloem-imported univalent ions into the seed apoplast. PMID:11842143

Relation of field-aligned currents measured by AMPERE project to solar wind and substorms

NASA Astrophysics Data System (ADS)

McPherron, R. L.; Anderson, B. J.; Chu, X.

2016-12-01

Magnetic perturbations measured in the Active Magnetosphere and Planetary Electrodynamics Response Experiment (AMPERE) by the Iridium constellation of spacecraft have been processed to obtain the time history of field-aligned currents (FAC) connecting the magnetosphere to the ionosphere. We find that the strength of these currents is closely related to the strength of the solar wind driver defined as a running average of the previous three hours of the optimum AL (auroral lower) coupling function. The relation is well represented by a saturation model I = A*S*Ss/(S+Ss) with I the current strength in mega Amps, S the driver strength in mV/m, Ss the saturation value of 7.78 mV/m, and A = 2.55 scales the relation to units of current. We also find that in general the upward current on the nightside increases with each substorm expansion onset defined by a combination of the SuperMag SML (SuperMag AL) and midlatitude positive bay (MPB) onset lists. A superposed epoch analysis using 700 onsets in 2010 shows the following: solar wind coupling peaks at expansion onset; dayside outward current starts to increase one hour before onset while nightside outward current starts suddenly at onset; nightside outward current reaches a peak at 28 minutes as do SML and MPB indices; FAC, SML, and MPB respectively take 1, 2, and 3 hours to decay to background. The data indicate that the substorm current wedge is superposed on a pre-existing field-aligned current system and that the location and properties of the current wedge can be studied with the AMPERE data.

Selective suppression of the slow-inactivating potassium currents by nootropics in molluscan neurons.

PubMed

Bukanova, Julia V; Solntseva, Elena I; Skrebitsky, Vladimir G

2002-09-01

The role of the voltage-gated K+ channels in the effect of some nootropics was investigated. Earlier, the multiple effect of high concentrations of two nootropics, piracetam and its peptide analogue GVS-111 [Seredenin et al. (1995), US Patent No. 5,439,930], on Ca2+ and K+ currents of molluscan neurons was shown [Solntseva et al. (1997), General Pharmacology 29, 85-89]. In the present work, we describe the selective effect of low concentrations of these nootropics as well as vinpocetine on certain types of K+ current. The experiments were performed on isolated neurons of the land snail Helix pomatia using a two-microelectrode voltage-clamp method. The inward voltage-gated Ca2+ current (ICa) and three subtypes of the outward voltage-gated K+ current were recorded: Ca2+-dependent K+ current (IK(Ca)), delayed rectifying current (IKD), and fast-inactivating K+ current (IA). It has been found that I Ca was not changed in the presence of 30 microM vinpocetine, 100 microM piracetam or 10 nM GVS-111, while slow-inactivating, TEA-sensitive IK(Ca) and IKD were inhibited (IK(Ca) more strongly than IKD). In contrast, the fast-inactivating, 4-AP-sensitive K+ current (IA) was not diminished by low concentrations of piracetam and GVS-111, while vinpocetine even augmented it. A possible role of slow-inactivating subtypes of the K+ channels in the development of different forms of dementia is discussed.

Zonal variations in K+ currents in vestibular crista calyx terminals

PubMed Central

Meredith, Frances L.

2014-01-01

We developed a rodent crista slice to investigate regional variations in electrophysiological properties of vestibular afferent terminals. Thin transverse slices of the gerbil crista ampullaris were made and electrical properties of calyx terminals in central zones (CZ) and peripheral zones (PZ) compared with whole cell patch clamp. Spontaneous action potential firing was observed in 25% of current-clamp recordings and was either regular or irregular in both zones. Firing was abolished when extracellular choline replaced Na+ but persisted when hair cell mechanotransduction channels or calyx AMPA receptors were blocked. This suggests that ion channels intrinsic to the calyx can generate spontaneous firing. In response to depolarizing voltage steps, outward K+ currents were observed at potentials above −60 mV. K+ currents in PZ calyces showed significantly more inactivation than currents in CZ calyces. Underlying K+ channel populations contributing to these differences were investigated. The KCNQ channel blocker XE991 dihydrochloride blocked a slowly activating, sustained outward current in both PZ and CZ calyces, indicating the presence of KCNQ channels. Mean reduction was greatest in PZ calyces. XE991 also reduced action potential firing frequency in CZ and PZ calyces and broadened mean action potential width. The K+ channel blocker 4-aminopyridine (10–50 μM) blocked rapidly activating, moderately inactivating currents that were more prevalent in PZ calyces. α-Dendrotoxin, a selective blocker of KV1 channels, reduced outward currents in CZ calyces but not in PZ calyces. Regional variations in K+ conductances may contribute to different firing responses in calyx afferents. PMID:25343781

Zonal variations in K+ currents in vestibular crista calyx terminals.

PubMed

Meredith, Frances L; Rennie, Katherine J

2015-01-01

We developed a rodent crista slice to investigate regional variations in electrophysiological properties of vestibular afferent terminals. Thin transverse slices of the gerbil crista ampullaris were made and electrical properties of calyx terminals in central zones (CZ) and peripheral zones (PZ) compared with whole cell patch clamp. Spontaneous action potential firing was observed in 25% of current-clamp recordings and was either regular or irregular in both zones. Firing was abolished when extracellular choline replaced Na(+) but persisted when hair cell mechanotransduction channels or calyx AMPA receptors were blocked. This suggests that ion channels intrinsic to the calyx can generate spontaneous firing. In response to depolarizing voltage steps, outward K(+) currents were observed at potentials above -60 mV. K(+) currents in PZ calyces showed significantly more inactivation than currents in CZ calyces. Underlying K(+) channel populations contributing to these differences were investigated. The KCNQ channel blocker XE991 dihydrochloride blocked a slowly activating, sustained outward current in both PZ and CZ calyces, indicating the presence of KCNQ channels. Mean reduction was greatest in PZ calyces. XE991 also reduced action potential firing frequency in CZ and PZ calyces and broadened mean action potential width. The K(+) channel blocker 4-aminopyridine (10-50 μM) blocked rapidly activating, moderately inactivating currents that were more prevalent in PZ calyces. α-Dendrotoxin, a selective blocker of KV1 channels, reduced outward currents in CZ calyces but not in PZ calyces. Regional variations in K(+) conductances may contribute to different firing responses in calyx afferents. Copyright © 2015 the American Physiological Society.

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

External K+ dependence of strong inward rectifier K+ channel conductance is caused not by K+ but by competitive pore blockade by external Na.

PubMed

Ishihara, Keiko

2018-06-15

Strong inward rectifier K + (sKir) channels determine the membrane potentials of many types of excitable and nonexcitable cells, most notably the resting potentials of cardiac myocytes. They show little outward current during membrane depolarization (i.e., strong inward rectification) because of the channel blockade by cytoplasmic polyamines, which depends on the deviation of the membrane potential from the K + equilibrium potential ( V - E K ) when the extracellular K + concentration ([K + ] out ) is changed. Because their open - channel conductance is apparently proportional to the "square root" of [K + ] out , increases/decreases in [K + ] out enhance/diminish outward currents through sKir channels at membrane potentials near their reversal potential, which also affects, for example, the repolarization and action-potential duration of cardiac myocytes. Despite its importance, however, the mechanism underlying the [K + ] out dependence of the open sKir channel conductance has remained elusive. By studying Kir2.1, the canonical member of the sKir channel family, we first show that the outward currents of Kir2.1 are observed under the external K + -free condition when its inward rectification is reduced and that the complete inhibition of the currents at 0 [K + ] out results solely from pore blockade caused by the polyamines. Moreover, the noted square-root proportionality of the open sKir channel conductance to [K + ] out is mediated by the pore blockade by the external Na + , which is competitive with the external K + Our results show that external K + itself does not activate or facilitate K + permeation through the open sKir channel to mediate the apparent external K + dependence of its open channel conductance. The paradoxical increase/decrease in outward sKir channel currents during alternations in [K + ] out , which is physiologically relevant, is caused by competition from impermeant extracellular Na . © 2018 Ishihara.

Kv2 Channel Regulation of Action Potential Repolarization and Firing Patterns in Superior Cervical Ganglion Neurons and Hippocampal CA1 Pyramidal Neurons

PubMed Central

Liu, Pin W.

2014-01-01

Kv2 family “delayed-rectifier” potassium channels are widely expressed in mammalian neurons. Kv2 channels activate relatively slowly and their contribution to action potential repolarization under physiological conditions has been unclear. We explored the function of Kv2 channels using a Kv2-selective blocker, Guangxitoxin-1E (GxTX-1E). Using acutely isolated neurons, mixed voltage-clamp and current-clamp experiments were done at 37°C to study the physiological kinetics of channel gating and action potentials. In both rat superior cervical ganglion (SCG) neurons and mouse hippocampal CA1 pyramidal neurons, 100 nm GxTX-1E produced near-saturating block of a component of current typically constituting ∼60–80% of the total delayed-rectifier current. GxTX-1E also reduced A-type potassium current (IA), but much more weakly. In SCG neurons, 100 nm GxTX-1E broadened spikes and voltage clamp experiments using action potential waveforms showed that Kv2 channels carry ∼55% of the total outward current during action potential repolarization despite activating relatively late in the spike. In CA1 neurons, 100 nm GxTX-1E broadened spikes evoked from −70 mV, but not −80 mV, likely reflecting a greater role of Kv2 when other potassium channels were partially inactivated at −70 mV. In both CA1 and SCG neurons, inhibition of Kv2 channels produced dramatic depolarization of interspike voltages during repetitive firing. In CA1 neurons and some SCG neurons, this was associated with increased initial firing frequency. In all neurons, inhibition of Kv2 channels depressed maintained firing because neurons entered depolarization block more readily. Therefore, Kv2 channels can either decrease or increase neuronal excitability depending on the time scale of excitation. PMID:24695716

State-changes in the swimmeret system: a neural circuit that drives locomotion

PubMed Central

Tschuluun, N.; Hall, W. M.; Mulloney, B.

2009-01-01

Summary The crayfish swimmeret system undergoes transitions between a silent state and an active state. In the silent state, no patterned firing occurs in swimmeret motor neurons. In the active state, bursts of spikes in power stroke motor neurons alternate periodically with bursts of spikes in return stroke motor neurons. In preparations of the isolated crayfish central nervous system (CNS), the temporal structures of motor patterns expressed in the active state are similar to those expressed by the intact animal. These transitions can occur spontaneously, in response to stimulation of command neurons, or in response to application of neuromodulators and transmitter analogues. We used single-electrode voltage clamp of power-stroke exciter and return-stroke exciter motor neurons to study changes in membrane currents during spontaneous transitions and during transitions caused by bath-application of carbachol or octopamine (OA). Spontaneous transitions from silence to activity were marked by the appearance of a standing inward current and periodic outward currents in both types of motor neurons. Bath-application of carbachol also led to the development of these currents and activation of the system. Using low Ca2+–high Mg2+ saline to block synaptic transmission, we found that the carbachol-induced inward current included a direct response by the motor neuron and an indirect component. Spontaneous transitions from activity to silence were marked by disappearance of the standing inward current and the periodic outward currents. Bath-application of OA led promptly to the disappearance of both currents, and silenced the system. OA also acted directly on both types of motor neurons to cause a hyperpolarizing outward current that would contribute to silencing the system. PMID:19880720

State-changes in the swimmeret system: a neural circuit that drives locomotion.

PubMed

Tschuluun, N; Hall, W M; Mulloney, B

2009-11-01

The crayfish swimmeret system undergoes transitions between a silent state and an active state. In the silent state, no patterned firing occurs in swimmeret motor neurons. In the active state, bursts of spikes in power stroke motor neurons alternate periodically with bursts of spikes in return stroke motor neurons. In preparations of the isolated crayfish central nervous system (CNS), the temporal structures of motor patterns expressed in the active state are similar to those expressed by the intact animal. These transitions can occur spontaneously, in response to stimulation of command neurons, or in response to application of neuromodulators and transmitter analogues. We used single-electrode voltage clamp of power-stroke exciter and return-stroke exciter motor neurons to study changes in membrane currents during spontaneous transitions and during transitions caused by bath-application of carbachol or octopamine (OA). Spontaneous transitions from silence to activity were marked by the appearance of a standing inward current and periodic outward currents in both types of motor neurons. Bath-application of carbachol also led to the development of these currents and activation of the system. Using low Ca(2+)-high Mg(2+) saline to block synaptic transmission, we found that the carbachol-induced inward current included a direct response by the motor neuron and an indirect component. Spontaneous transitions from activity to silence were marked by disappearance of the standing inward current and the periodic outward currents. Bath-application of OA led promptly to the disappearance of both currents, and silenced the system. OA also acted directly on both types of motor neurons to cause a hyperpolarizing outward current that would contribute to silencing the system.

Cardiomyocyte dysfunction during the chronic phase of Chagas disease.

PubMed

Roman-Campos, Danilo; Sales-Júnior, Policarpo; Duarte, Hugo Leonardo; Gomes, Eneas Ricardo; Guatimosim, Silvia; Ropert, Catherine; Gazzinelli, Ricardo Tostes; Cruz, Jader Santos

2013-04-01

Chagas disease, which is caused by the parasite Trypanosoma cruzi, is an important cause of heart failure. We investigated modifications in the cellular electrophysiological and calcium-handling characteristics of an infected mouse heart during the chronic phase of the disease. The patch-clamp technique was used to record action potentials (APs) and L-type Ca2+ and transient outward K+ currents. [Ca2+]i changes were determined using confocal microscopy. Infected ventricular cells showed prolonged APs, reduced transient outward K+ and L-type Ca2+ currents and reduced Ca2+ release from the sarcoplasmic reticulum. Thus, the chronic phase of Chagas disease is characterised by cardiomyocyte dysfunction, which could lead to heart failure.

Cardiomyocyte dysfunction during the chronic phase of Chagas disease

PubMed Central

Roman-Campos, Danilo; Sales-Júnior, Policarpo; Duarte, Hugo Leonardo; Gomes, Eneas Ricardo; Guatimosim, Silvia; Ropert, Catherine; Gazzinelli, Ricardo Tostes; Cruz, Jader Santos

2013-01-01

Chagas disease, which is caused by the parasite Trypanosoma cruzi, is an important cause of heart failure. We investigated modifications in the cellular electrophysiological and calcium-handling characteristics of an infected mouse heart during the chronic phase of the disease. The patch-clamp technique was used to record action potentials (APs) and L-type Ca2+ and transient outward K+ currents. [Ca2+]i changes were determined using confocal microscopy. Infected ventricular cells showed prolonged APs, reduced transient outward K+ and L-type Ca2+ currents and reduced Ca2+ release from the sarcoplasmic reticulum. Thus, the chronic phase of Chagas disease is characterised by cardiomyocyte dysfunction, which could lead to heart failure. PMID:23579807

Conformational changes of an ion-channel during gating and emerging electrophysiologic properties: Application of a computational approach to cardiac Kv7.1.

PubMed

Nekouzadeh, Ali; Rudy, Yoram

2016-01-01

Ion channels are the "building blocks" of the excitation process in excitable tissues. Despite advances in determining their molecular structure, understanding the relationship between channel protein structure and electrical excitation remains a challenge. The Kv7.1 potassium channel is an important determinant of the cardiac action potential and its adaptation to rate changes. It is subject to beta adrenergic regulation, and many mutations in the channel protein are associated with the arrhythmic long QT syndrome. In this theoretical study, we use a novel computational approach to simulate the conformational changes that Kv7.1 undergoes during activation gating and compute the resulting electrophysiologic function in terms of single-channel and macroscopic currents. We generated all possible conformations of the S4-S5 linker that couples the S3-S4 complex (voltage sensor domain, VSD) to the pore, and all associated conformations of VSD and the pore (S6). Analysis of these conformations revealed that VSD-to-pore mechanical coupling during activation gating involves outward translation of the voltage sensor, accompanied by a translation away from the pore and clockwise twist. These motions cause pore opening by moving the S4-S5 linker upward and away from the pore, providing space for the S6 tails to move away from each other. Single channel records, computed from the simulated motion trajectories during gating, have stochastic properties similar to experimentally recorded traces. Macroscopic current through an ensemble of channels displays two key properties of Kv7.1: an initial delay of activation and fast inactivation. The simulations suggest a molecular mechanism for fast inactivation; a large twist of the VSD following its outward translation results in movement of the base of the S4-S5 linker toward the pore, eliminating open pore conformations to cause inactivation. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Suppressive Effect of Carvedilol on Na+/Ca2+ Exchange Current in Isolated Guinea-Pig Cardiac Ventricular Myocytes.

PubMed

Tashiro, Miyuki; Watanabe, Yasuhide; Yamakawa, Tomomi; Yamashita, Kanna; Kita, Satomi; Iwamoto, Takahiro; Kimura, Junko

2017-01-01

Carvedilol ((+/-)-1-(carbazol-4-yloxy)-3-[[2-(o-methoxyphenoxy)ethyl]amino]-2-propanol), a β-adrenoceptor-blocker, has multi-channel blocking and vasodilator properties. This agent dose-dependently improves left ventricular function and reduces mortality in patients with arrhythmia and chronic heart failure. However, the effect of carvedilol on the cardiac Na+/Ca2+ exchanger (NCX1) has not been investigated. We examined the effects of carvedilol and metoprolol, 2 β-blockers, on Na+/Ca2+ exchange current (INCX) in guinea-pig cardiac ventricular cells and fibroblasts expressing dog cardiac NCX1. Carvedilol suppressed INCX in a concentration-dependent manner but metoprolol did not. IC50 values for the Ca2+ influx (outward) and efflux (inward) components of INCX were 69.7 and 61.5 µmol/l, respectively. Carvedilol at 100 μmol/l inhibited INCX in CCL39 cells expressing wild type NCX1 similar to mutant NCX1 without the intracellular regulatory loop. Carvedilol at 30 µmol/l abolished ouabain-induced delayed afterdepolarizations. Carvedilol inhibited cardiac NCX in a concentration-dependent manner in isolated cardiac ventricles, but metoprolol did not. We conclude that carvedilol inhibits NCX1 at supratherapeutic concentrations. © 2016 S. Karger AG, Basel.

An ether -à-go-go K+ current, Ih-eag, contributes to the hyperpolarization of human fusion-competent myoblasts

PubMed Central

Bijlenga, Philippe; Occhiodoro, Teresa; Liu, Jian-Hui; Bader, Charles R; Bernheim, Laurent; Fischer-Lougheed, Jacqueline

1998-01-01

Two early signs of human myoblast commitment to fusion are membrane potential hyperpolarization and concomitant expression of a non-inactivating delayed rectifier K+ current, IK(NI). This current closely resembles the outward K+ current elicited by rat ether-à-go-go (r-eag) channels in its range of potential for activation and unitary conductance.It is shown that activation kinetics of IK(NI), like those of r-eag, depend on holding potential and on [Mg2+]o, and that IK(NI), like r-eag, is reversibly inhibited by a rise in [Ca2+].Forced expression of an isolated human ether-à-go-go K+ channel (h-eag) cDNA in undifferentiated myoblasts generates single-channel and whole-cell currents with remarkable similarity to IK(NI).h-eag current (Ih-eag) is reversibly inhibited by a rise in [Ca2+]i, and the activation kinetics depend on holding potential and [Mg2+]o.Forced expression of h-eag hyperpolarizes undifferentiated myoblasts from −9 to −50 mV, the threshold for the activation of both Ih-eag and IK(NI). Similarly, the higher the density of IK(NI), the more hyperpolarized the resting potential of fusion-competent myoblasts.It is concluded that h-eag constitutes the channel underlying IK(NI) and that it contributes to the hyperpolarization of fusion-competent myoblasts. To our knowledge, this is the first demonstration of a physiological role for a mammalian eag K+ channel. PMID:9763622

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.

Voltage-gated currents in identified rat olfactory receptor neurons.

PubMed

Trombley, P Q; Westbrook, G L

1991-02-01

Whole-cell recording techniques were used to characterize voltage-gated membrane currents in neonatal rat olfactory receptor neurons (ORNs) in cell culture. Mature ORNs were identified in culture by their characteristic bipolar morphology, by retrograde labeling techniques, and by olfactory marker protein (OMP) immunoreactivity. ORNs did not have spontaneous activity, but fired action potentials to depolarizing current pulses. Action potentials were blocked by tetrodotoxin (TTX), which contrasts with the TTX-resistant action potentials in salamander olfactory receptor cells (e.g., Firestein and Werblin, 1987). Prolonged, suprathreshold current pulses evoked only a single action potential; however, repetitive firing up to 35 Hz could be elicited by a series of brief depolarizing pulses. Under voltage clamp, the TTX-sensitive sodium current had activation and inactivation properties similar to other excitable cells. In TTX and 20 mM barium, sustained inward current were evoked by voltage steps positive to -30 mV. This current was blocked by Cd (100 microM) and by nifedipine (IC50 = 368 nM) consistent with L-type calcium channels in other neurons. No T-type calcium current was observed. Voltage steps positive to -20 mV also evoked an outward current that did not inactivate during 100-msec depolarizations. Tail current analysis of this current was consistent with a selective potassium conductance. The outward current was blocked by external tetraethylammonium but was unaffected by Cd or 4-aminopyridine (4-AP) or by removal of external calcium. A transient outward current was not observed. The 3 voltage-dependent conductances in cultured rat ORNs appear to be sufficient for 2 essential functions: action potential generation and transmitter release. As a single odorant-activated channel can trigger an action potential (e.g., Lynch and Barry, 1989), the repetitive firing seen with brief depolarizing pulses suggests that ORNs do not integrate sensory input, but rather act as high-fidelity relays such that each opening of an odorant-activated channel reaches the olfactory bulb glomeruli as an action potential.

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

Supply-demand balance in outward-directed networks and Kleiber's law

PubMed Central

Painter, Page R

2005-01-01

Background Recent theories have attempted to derive the value of the exponent α in the allometric formula for scaling of basal metabolic rate from the properties of distribution network models for arteries and capillaries. It has recently been stated that a basic theorem relating the sum of nutrient currents to the specific nutrient uptake rate, together with a relationship claimed to be required in order to match nutrient supply to nutrient demand in 3-dimensional outward-directed networks, leads to Kleiber's law (b = 3/4). Methods The validity of the supply-demand matching principle and the assumptions required to prove the basic theorem are assessed. The supply-demand principle is evaluated by examining the supply term and the demand term in outward-directed lattice models of nutrient and water distribution systems and by applying the principle to fractal-like models of mammalian arterial systems. Results Application of the supply-demand principle to bifurcating fractal-like networks that are outward-directed does not predict 3/4-power scaling, and evaluation of water distribution system models shows that the matching principle does not match supply to demand in such systems. Furthermore, proof of the basic theorem is shown to require that the covariance of nutrient uptake and current path length is 0, an assumption unlikely to be true in mammalian arterial systems. Conclusion The supply-demand matching principle does not lead to a satisfactory explanation for the approximately 3/4-power scaling of mammalian basal metabolic rate. PMID:16283939

Supply-demand balance in outward-directed networks and Kleiber's law.

PubMed

Painter, Page R

2005-11-10

Recent theories have attempted to derive the value of the exponent alpha in the allometric formula for scaling of basal metabolic rate from the properties of distribution network models for arteries and capillaries. It has recently been stated that a basic theorem relating the sum of nutrient currents to the specific nutrient uptake rate, together with a relationship claimed to be required in order to match nutrient supply to nutrient demand in 3-dimensional outward-directed networks, leads to Kleiber's law (b = 3/4). The validity of the supply-demand matching principle and the assumptions required to prove the basic theorem are assessed. The supply-demand principle is evaluated by examining the supply term and the demand term in outward-directed lattice models of nutrient and water distribution systems and by applying the principle to fractal-like models of mammalian arterial systems. Application of the supply-demand principle to bifurcating fractal-like networks that are outward-directed does not predict 3/4-power scaling, and evaluation of water distribution system models shows that the matching principle does not match supply to demand in such systems. Furthermore, proof of the basic theorem is shown to require that the covariance of nutrient uptake and current path length is 0, an assumption unlikely to be true in mammalian arterial systems. The supply-demand matching principle does not lead to a satisfactory explanation for the approximately 3/4-power scaling of mammalian basal metabolic rate.

Electrogenic properties of the Na+/K+ ATPase control transitions between normal and pathological brain states

PubMed Central

Krishnan, Giri P.; Filatov, Gregory; Shilnikov, Andrey

2015-01-01

Ionic concentrations fluctuate significantly during epileptic seizures. In this study, using a combination of in vitro electrophysiology, computer modeling, and dynamical systems analysis, we demonstrate that changes in the potassium and sodium intra- and extracellular ion concentrations ([K+] and [Na+], respectively) during seizure affect the neuron dynamics by modulating the outward Na+/K+ pump current. First, we show that an increase of the outward Na+/K+ pump current mediates termination of seizures when there is a progressive increase in the intracellular [Na+]. Second, we show that the Na+/K+ pump current is crucial in maintaining the stability of the physiological network state; a reduction of this current leads to the onset of seizures via a positive-feedback loop. We then present a novel dynamical mechanism for bursting in neurons with a reduced Na+/K+ pump. Overall, our study demonstrates the profound role of the current mediated by Na+/K+ ATPase on the stability of neuronal dynamics that was previously unknown. PMID:25589588

Moderate hypoxia influences excitability and blocks dendrotoxin sensitive K+ currents in rat primary sensory neurones

PubMed Central

Gruss, Marco; Ettorre, Giovanni; Stehr, Annette Jana; Henrich, Michael; Hempelmann, Gunter; Scholz, Andreas

2006-01-01

Hypoxia alters neuronal function and can lead to neuronal injury or death especially in the central nervous system. But little is known about the effects of hypoxia in neurones of the peripheral nervous system (PNS), which survive longer hypoxic periods. Additionally, people have experienced unpleasant sensations during ischemia which are dedicated to changes in conduction properties or changes in excitability in the PNS. However, the underlying ionic conductances in dorsal root ganglion (DRG) neurones have not been investigated in detail. Therefore we investigated the influence of moderate hypoxia (27.0 ± 1.5 mmHg) on action potentials, excitability and ionic conductances of small neurones in a slice preparation of DRGs of young rats. The neurones responded within a few minutes non-uniformly to moderate hypoxia: changes of excitability could be assigned to decreased outward currents in most of the neurones (77%) whereas a smaller group (23%) displayed increased outward currents in Ringer solution. We were able to attribute most of the reduction in outward-current to a voltage-gated K+ current which activated at potentials positive to -50 mV and was sensitive to 50 nM α-dendrotoxin (DTX). Other toxins that inhibit subtypes of voltage gated K+ channels, such as margatoxin (MgTX), dendrotoxin-K (DTX-K), r-tityustoxin Kα (TsTX-K) and r-agitoxin (AgTX-2) failed to prevent the hypoxia induced reduction. Therefore we could not assign the hypoxia sensitive K+ current to one homomeric KV channel type in sensory neurones. Functionally this K+ current blockade might underlie the increased action potential (AP) duration in these neurones. Altogether these results, might explain the functional impairment of peripheral neurones under moderate hypoxia. PMID:16579848

Homing in humans: A different look.

PubMed

Bovet, J

1994-08-01

A current model holds that the long-distance homing abilities of free-ranging mammals rest primarily on a strategy of course reversal, based on outward journey information. In this study, I measured the ability to orient toward home in humans displaced under conditions that promote the use of this strategy, namely along an outward route that was direct, and the main bearing of which could be extrapolated by reference to a pre-existant mental map and by visual backup during the outward journey. Even though the individual course estimates obtained did show a certain amount of dispersion and/or error, they were more accurate and less dispersed than in experiments by other authors, where subjects could not use this strategy, because they were displaced blindfolded and/or along circuitous routes. Copyright © 1994. Published by Elsevier B.V.

Bradykinin induced a positive chronotropic effect via stimulation of T- and L-type calcium currents in heart cells.

PubMed

El-Bizri, Nesrine; Bkaily, Ghassan; Wang, Shimin; Jacques, Danielle; Regoli, Domenico; D'Orléans-Juste, Pedro; Sukarieh, Rami

2003-03-01

Using Fluo-3 calcium dye confocal microscopy and spontaneously contracting embryonic chick heart cells, bradykinin (10(-10) M) was found to induce positive chronotropic effects by increasing the frequency of the transient increase of cytosolic and nuclear free Ca2+. Pretreatment of the cells with either B1 or B2 receptor antagonists (R126 and R817, respectively) completely prevented bradykinin (BK) induced positive chronotropic effects on spontaneously contracting single heart cells. Using the whole-cell voltage clamp technique and ionic substitution to separate the different ionic current species, our results showed that BK (10(-6) M) had no effect on fast Na+ inward current and delayed outward potassium current. However, both L- and T-type Ca2+ currents were found to be increased by BK in a dose-dependent manner (10(-10)-10(-7) M). The effects of BK on T- and L-type Ca2+ currents were partially blocked by the B1 receptor antagonist [Leu8]des-Arg9-BK (R592) (10(-7) M) and completely reversed by the B2 receptor antagonist D-Arg[Hyp3,D-Phe7,Leu8]BK (R-588) (10(-7) M) or pretreatment with pertussis toxin (PTX). These results demonstrate that BK induced a positive chronotropic effect via stimulation of T- and L-type Ca2+ currents in heart cells mainly via stimulation of B2 receptor coupled to PTX-sensitive G-proteins. The increase of both types of Ca2+ current by BK in heart cells may explain the positive inotropic and chronotropic effects of this hormone.

Enhanced differentiation potential of human amniotic mesenchymal stromal cells by using three-dimensional culturing.

PubMed

Lin, Xue; Li, Hao Yu; Chen, Lian Feng; Liu, Bo Jiang; Yao, Yian; Zhu, Wen Ling

2013-06-01

The therapeutic potential of human amniotic mesenchymal stromal cells (hAMSCs) remains limited because of their differentiation towards mesenchymal stem cells (MSCs) following adherence. The aim of this study was to develop a three-dimensional (3-D) culture system that would permit hAMSCs to differentiate into cardiomyocyte-like cells. hAMSCs were isolated from human amnions of full-term births collected after Cesarean section. Immunocytochemistry, immunofluorescence and flow cytometry analyses were undertaken to examine hAMSC marker expression for differentiation status after adherence. Membrane currents were determined by patch clamp analysis of hAMSCs grown with or without cardiac lysates. Freshly isolated hAMSCs were positive for human embryonic stem-cell-related markers but their marker profile significantly shifted towards that of MSCs following adherence. hAMSCs cultured in the 3-D culture system in the presence of cardiac lysate expressed cardiomyocyte-specific markers, in contrast to those maintained in standard adherent cultures or those in 3-D cultures without cardiac lysate. hAMSCs cultured in 3-D with cardiac lysate displayed a cardiomyocyte-like phenotype as observed by membrane currents, including a calcium-activated potassium current, a delayed rectifier potassium current and a Ca(2+)-resistant transient outward K(+) current. Thus, although adherence limits the potential of hAMSCs to differentiate into cardiomyocyte-like cells, the 3-D culture of hAMSCs represents a more effective method of their culture for use in regenerative medicine.

Postnatal development of A-type and Kv1- and Kv2-mediated potassium channel currents in neocortical pyramidal neurons

PubMed Central

Guan, Dongxu; Horton, Leslie R.; Armstrong, William E.

2011-01-01

Potassium channels regulate numerous aspects of neuronal excitability, and several voltage-gated K+ channel subunits have been identified in pyramidal neurons of rat neocortex. Previous studies have either considered the development of outward current as a whole or divided currents into transient, A-type and persistent, delayed rectifier components but did not differentiate between current components defined by α-subunit type. To facilitate comparisons of studies reporting K+ currents from animals of different ages and to understand the functional roles of specific current components, we characterized the postnatal development of identified Kv channel-mediated currents in pyramidal neurons from layers II/III from rat somatosensory cortex. Both the persistent/slowly inactivating and transient components of the total K+ current increased in density with postnatal age. We used specific pharmacological agents to test the relative contributions of putative Kv1- and Kv2-mediated currents (100 nM α-dendrotoxin and 600 nM stromatoxin, respectively). A combination of voltage protocol, pharmacology, and curve fitting was used to isolate the rapidly inactivating A-type current. We found that the density of all identified current components increased with postnatal age, approaching a plateau at 3–5 wk. We found no significant changes in the relative proportions or kinetics of any component between postnatal weeks 1 and 5, except that the activation time constant for A-type current was longer at 1 wk. The putative Kv2-mediated component was the largest at all ages. Immunocytochemistry indicated that protein expression for Kv4.2, Kv4.3, Kv1.4, and Kv2.1 increased between 1 wk and 4–5 wk of age. PMID:21451062

Postnatal development of A-type and Kv1- and Kv2-mediated potassium channel currents in neocortical pyramidal neurons.

PubMed

Guan, Dongxu; Horton, Leslie R; Armstrong, William E; Foehring, Robert C

2011-06-01

Potassium channels regulate numerous aspects of neuronal excitability, and several voltage-gated K(+) channel subunits have been identified in pyramidal neurons of rat neocortex. Previous studies have either considered the development of outward current as a whole or divided currents into transient, A-type and persistent, delayed rectifier components but did not differentiate between current components defined by α-subunit type. To facilitate comparisons of studies reporting K(+) currents from animals of different ages and to understand the functional roles of specific current components, we characterized the postnatal development of identified Kv channel-mediated currents in pyramidal neurons from layers II/III from rat somatosensory cortex. Both the persistent/slowly inactivating and transient components of the total K(+) current increased in density with postnatal age. We used specific pharmacological agents to test the relative contributions of putative Kv1- and Kv2-mediated currents (100 nM α-dendrotoxin and 600 nM stromatoxin, respectively). A combination of voltage protocol, pharmacology, and curve fitting was used to isolate the rapidly inactivating A-type current. We found that the density of all identified current components increased with postnatal age, approaching a plateau at 3-5 wk. We found no significant changes in the relative proportions or kinetics of any component between postnatal weeks 1 and 5, except that the activation time constant for A-type current was longer at 1 wk. The putative Kv2-mediated component was the largest at all ages. Immunocytochemistry indicated that protein expression for Kv4.2, Kv4.3, Kv1.4, and Kv2.1 increased between 1 wk and 4-5 wk of age.

Electrophysiological responses of dissociated type I cells of the rabbit carotid body to cyanide.

PubMed Central

Biscoe, T J; Duchen, M R

1989-01-01

1. The carotid body is the major peripheral sensor of arterial PO2 in the mammal and is excited by cyanide (CN-). Type I cells, the presumed sites for transduction, were freshly dissociated from the carotid body of the adult rabbit and studied with the whole-cell patch clamp technique. 2. Type I cells were hyperpolarized by CN-, the action potential was shortened, and there was an increased after-hyperpolarization. 3. Under voltage clamp control, CN- increased a voltage-dependent outward current, which showed pronounced outward rectification. Tail currents increased by CN- reversed close to the predicted EK, the reversal potential of the CN--induced current depended on extracellular [K+], and the current was blocked by intracellular TEA+ and Cs+. 4. The i-V relation of the CN--induced conductance strongly mirrored that of voltage-gated Ca2+ entry, and the response was abolished by removal of extracellular Ca2+. We conclude that the increased gK is Ca2+ -dependent (gK(Ca]. 5. The Ca2+ current was attenuated by CN-, and showed an increased rate of inactivation. Thus, the increased gK(Ca) must result from an alteration in Ca2+ homeostasis independent of the Ca2+ current, and not an increased Ca2+ entry through voltage-activated channels. 6. Carbachol also hyperpolarized cells and increased a K+ conductance. 7. At depolarized holding potentials a steady-state outward current was increased by CN-. The current reversed close to EK, and was associated with increased current fluctuations. Noise analysis showed that a channel conductance of 3 pS carries the current. 8. The response to CN- was not impaired by the inclusion of 5 mM-MgATP in the patch pipette. 9. If signals to the CNS are initiated by the calcium-dependent release of transmitters from type I cells, transduction would appear to be the direct consequence of the energy dependence of Ca2+ homeostasis. PMID:2557439

Chloride channel blockers activate an endogenous cationic current in oocytes of Bufo arenarum.

PubMed

Cavarra, M S; del Mónaco, S M; Kotsias, B A

2004-07-01

A two-electrode, voltage-clamp technique was used to measure the effect of the Cl(-) channel blockers, 9-anthracene carboxylic acid and niflumic acid, upon the ionic currents of oocytes of the South American toad Bufo arenarum. The main results were: (1) both blockers produced a reversible increase of the outward currents on a dose-dependent manner; (2) the activated outward current was voltage dependent; (3) the 9-anthracene carboxylic acid-sensitive current was blocked with barium; and (4) the effect of 9-anthracene carboxylic acid was more pronounced in a zero-K(+) solution than in standard (2 mmol l(-1)) or high (20 mmol l(-1)) K(+) solutions, indicating that a K(+) conductance is activated. The effect of the Cl(-) channel blockers could be due to a direct interaction with endogenous cationic channels. Another possible explanation is that Cl(-) that enter the cell during depolarizing steps in control solution inhibit this cationic conductance; thus, the blockade of Cl(-) channels by 9-anthracene carboxylic acid and niflumic acid would remove this inhibition, allowing the cationic current to flow freely.

Sodium-bicarbonate cotransport in retinal Müller (glial) cells of the salamander.

PubMed

Newman, E A

1991-12-01

An electrogenic Na+/HCO3- cotransport system was studied in freshly dissociated Müller cells of the salamander retina. Cotransporter currents were recorded from isolated cells using the whole-cell, voltage-clamp technique following the block of K+ conductance with external Ba2+ and internal Cs+. At constant pHo, an outward current was evoked when extracellular HCO3- concentration was raised by pressure ejecting a HCO3(-)-buffered solution onto the surface of cells bathed in nominally HCO3(-)-free solution. The HCO3(-)-evoked outward current was reduced to 4.4% of control by 0.5 mM DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulfonate), to 28.8% of control by 2 mM DNDS (4,4'-dinitrostilbene-2,2'-disulfonate), and to 28.4% of control by 2 mM harmaline. Substitution of choline for Na+ in bath and ejection solutions reduced the response to 1.3% of control. Bicarbonate-evoked currents of normal magnitude were recorded when methane sulfonate was substituted for Cl- in bath, ejection, and intracellular solutions. Similarly, an outward current was evoked when extracellular Na+ concentration was raised in the presence of HCO3-. The Na(+)-evoked response was reduced to 16.2% of control by 2 mM DNDS and was abolished by removal of HCO3- from bath and ejection solutions. Taken together, these results (block by stilbenes and harmaline, HCO3- and Na+ dependence, Cl- independence) indicate that salamander Müller cells possess an electrogenic Na+/HCO3- cotransport system. Na+/HCO3- cotransporter sites were localized primarily at the endfoot region of Müller cells. Ejection of HCO3- onto the endfoot evoked outward currents 10 times larger than currents evoked by ejections onto the opposite (distal) end of the cell. The reversal potential of the cotransporter was determined by DNDS block of cotransport current. In the absence of a transmembrane HCO3- gradient, the reversal potential varied systematically as a function of the transmembrane Na+ gradient. The reversal potential was -0.1 mV for a [Na+]o:[Na+]i ratio of 1:1 and -25.2 mV for a Na+ gradient ratio of 7.4:1. Based on these values, the estimated stoichiometry of the cotransporter was 2.80 +/- 0.13:1 (HCO3-:Na+). Possible functions of the glial cell Na+/HCO3- cotransporter, including the regulation of CO2 in the retina and the regulation of cerebral blood flow, are discussed.

Selective activation of heteromeric SK channels contributes to action potential repolarization in mouse atrial myocytes.

PubMed

Hancock, Jane M; Weatherall, Kate L; Choisy, Stéphanie C; James, Andrew F; Hancox, Jules C; Marrion, Neil V

2015-05-01

Activation of small conductance calcium-activated potassium (SK) channels is proposed to contribute to repolarization of the action potential in atrial myocytes. This role is controversial, as these cardiac SK channels appear to exhibit an uncharacteristic pharmacology. The objectives of this study were to resolve whether activation of SK channels contributes to atrial action potential repolarization and to determine the likely subunit composition of the channel. The effect of 2 SK channel inhibitors was assessed on outward current evoked in voltage clamp and on action potential duration in perforated patch and whole-cell current clamp recording from acutely isolated mouse atrial myocytes. The presence of SK channel subunits was assessed using immunocytochemistry. A significant component of outward current was reduced by the SK channel blockers apamin and UCL1684. Block by apamin displayed a sensitivity indicating that this current was carried by homomeric SK2 channels. Action potential duration was significantly prolonged by UCL1684, but not by apamin. This effect was accompanied by an increase in beat-to-beat variability and action potential triangulation. This pharmacology was matched by that of expressed heteromeric SK2-SK3 channels in HEK293 cells. Immunocytochemistry showed that atrial myocytes express both SK2 and SK3 channels with an overlapping expression pattern. Only proposed heteromeric SK2-SK3 channels are physiologically activated to contribute to action potential repolarization, which is indicated by the difference in pharmacology of evoked outward current and prolongation of atrial action potential duration. The effect of blocking this channel on the action potential suggests that SK channel inhibition during cardiac function has the potential to be proarrhythmic. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

The investigation of the cellular electrophysiological and antiarrhythmic effects of a novel selective sodium-calcium exchanger inhibitor, GYKB-6635, in canine and guinea-pig hearts.

PubMed

Geramipour, Amir; Kohajda, Zsófia; Corici, Claudia; Prorok, János; Szakonyi, Zsolt; Oravecz, Kinga; Márton, Zoltán; Nagy, Norbert; Tóth, András; Acsai, Károly; Virág, László; Varró, András; Jost, Norbert

2016-10-01

The sodium-calcium exchanger (NCX) is considered as the major transmembrane transport mechanism that controls Ca 2+ homeostasis. Its contribution to the cardiac repolarization has not yet been directly studied due to lack of specific inhibitors, so that an urgent need for more selective compounds. In this study, the electrophysiological effects of GYKB-6635, a novel NCX inhibitor, on the NCX, L-type calcium, and main repolarizing potassium currents as well as action potential (AP) parameters were investigated. Ion currents and AP recordings were investigated by applying the whole-cell patch clamp and standard microelectrode techniques in canine heart at 37 °C. Effects of GYKB-6635 were studied in ouabain-induced arrhythmias in isolated guinea-pig hearts. At a concentration of 1 μmol/L, GYKB significantly reduced both the inward and outward NCX currents (57% and 58%, respectively). Even at a high concentration (10 μmol/L), GYKB-6635 did not change the I CaL , the maximum rate of depolarization (dV/dt max ), the main repolarizing K + currents, and the main AP parameters. GYKB-6635 pre-treatment significantly delayed the time to the development of ventricular fibrillation (by about 18%). It is concluded that GYKB-6635 is a potent and highly selective inhibitor of the cardiac NCX and, in addition, it is suggested to also contribute to the prevention of DAD-based arrhythmias.

Differential Expression of Inward and Outward Potassium Currents in the Macrophage-like Cell Line J774.1

DTIC Science & Technology

1985-04-02

skeletal muscle (Adrian, Hodgkin & Chandler, 1970), and nerve (Goldman & Schauf , 1973; Thompson, 1977). The general mathematical formalism describes the...594-609. Goldman, L. & Schauf , C. L. (1973) Quantitative description of sodium and potassium currents and computed action potentials in Myxicola giant

Time-resolved measurement of single pulse femtosecond laser-induced periodic surface structure formation induced by a pre-fabricated surface groove.

PubMed

Kafka, K R P; Austin, D R; Li, H; Yi, A Y; Cheng, J; Chowdhury, E A

2015-07-27

Time-resolved diffraction microscopy technique has been used to observe the formation of laser-induced periodic surface structures (LIPSS) from the interaction of a single femtosecond laser pulse (pump) with a nano-scale groove mechanically formed on a single-crystal Cu substrate. The interaction dynamics (0-1200 ps) was captured by diffracting a time-delayed, frequency-doubled pulse (probe) from nascent LIPSS formation induced by the pump with an infinity-conjugate microscopy setup. The LIPSS ripples are observed to form asynchronously, with the first one forming after 50 ps and others forming sequentially outward from the groove edge at larger time delays. A 1-D analytical model of electron heating including both the laser pulse and surface plasmon polariton excitation at the groove edge predicts ripple period, melt spot diameter, and qualitatively explains the asynchronous time-evolution of LIPSS formation.

Atrial fibrillation: Therapeutic potential of atrial K+ channel blockers.

PubMed

Ravens, Ursula; Odening, Katja E

2017-08-01

Despite the epidemiological scale of atrial fibrillation, current treatment strategies are of limited efficacy and safety. Ideally, novel drugs should specifically correct the pathophysiological mechanisms responsible for atrial fibrillation with no other cardiac or extracardiac actions. Atrial-selective drugs are directed toward cellular targets with sufficiently different characteristics in atria and ventricles to modify only atrial function. Several potassium (K + ) channels with either predominant expression in atria or distinct electrophysiological properties in atria and ventricles can serve as atrial-selective drug targets. These channels include the ultra-rapidly activating, delayed outward-rectifying Kv1.5 channel conducting I Kur , the acetylcholine-activated inward-rectifying Kir3.1/Kir3.4 channel conducting I K,ACh , the Ca 2+ -activated K + channels of small conductance (SK) conducting I SK , and the two pore domain K + (K2P) channels TWIK-1, TASK-1 and TASK-3 that are responsible for voltage-independent background currents I TWIK-1 , I TASK-1 , and I TASK-3 . Here, we briefly review the characteristics of these K + channels and their roles in atrial fibrillation. The antiarrhythmic potential of drugs targeting the described channels is discussed as well as their putative value in treatment of atrial fibrillation. Copyright © 2016 Elsevier Inc. All rights reserved.

Initial segment Kv2.2 channels mediate a slow delayed rectifier and maintain high frequency action potential firing in medial nucleus of the trapezoid body neurons

PubMed Central

Johnston, Jamie; Griffin, Sarah J; Baker, Claire; Skrzypiec, Anna; Chernova, Tatanya; Forsythe, Ian D

2008-01-01

The medial nucleus of the trapezoid body (MNTB) is specialized for high frequency firing by expression of Kv3 channels, which minimize action potential (AP) duration, and Kv1 channels, which suppress multiple AP firing, during each calyceal giant EPSC. However, the outward K+ current in MNTB neurons is dominated by another unidentified delayed rectifier. It has slow kinetics and a peak conductance of ∼37 nS; it is half-activated at −9.2 ± 2.1 mV and half-inactivated at −35.9 ± 1.5 mV. It is blocked by several non-specific potassium channel antagonists including quinine (100 μm) and high concentrations of extracellular tetraethylammonium (TEA; IC50 = 11.8 mm), but no specific antagonists were found. These characteristics are similar to recombinant Kv2-mediated currents. Quantitative RT-PCR showed that Kv2.2 mRNA was much more prevalent than Kv2.1 in the MNTB. A Kv2.2 antibody showed specific staining and Western blots confirmed that it recognized a protein ∼110 kDa which was absent in brainstem tissue from a Kv2.2 knockout mouse. Confocal imaging showed that Kv2.2 was highly expressed in axon initial segments of MNTB neurons. In the absence of a specific antagonist, Hodgkin–Huxley modelling of voltage-gated conductances showed that Kv2.2 has a minor role during single APs (due to its slow activation) but assists recovery of voltage-gated sodium channels (Nav) from inactivation by hyperpolarizing interspike potentials during repetitive AP firing. Current-clamp recordings during high frequency firing and characterization of Nav inactivation confirmed this hypothesis. We conclude that Kv2.2-containing channels have a distinctive initial segment location and crucial function in maintaining AP amplitude by regulating the interspike potential during high frequency firing. PMID:18511484

Effects of pioglitazone on cardiac ion currents and action potential morphology in canine ventricular myocytes.

PubMed

Kistamás, Kornél; Szentandrássy, Norbert; Hegyi, Bence; Ruzsnavszky, Ferenc; Váczi, Krisztina; Bárándi, László; Horváth, Balázs; Szebeni, Andrea; Magyar, János; Bányász, Tamás; Kecskeméti, Valéria; Nánási, Péter P

2013-06-15

Despite its widespread therapeutical use there is little information on the cellular cardiac effects of the antidiabetic drug pioglitazone in larger mammals. In the present study, therefore, the concentration-dependent effects of pioglitazone on ion currents and action potential configuration were studied in isolated canine ventricular myocytes using standard microelectrode, conventional whole cell patch clamp, and action potential voltage clamp techniques. Pioglitazone decreased the maximum velocity of depolarization and the amplitude of phase-1 repolarization at concentrations ≥3 μM. Action potentials were shortened by pioglitazone at concentrations ≥10 μM, which effect was accompanied with significant reduction of beat-to-beat variability of action potential duration. Several transmembrane ion currents, including the transient outward K(+) current (Ito), the L-type Ca(2+) current (ICa), the rapid and slow components of the delayed rectifier K(+) current (IKr and IKs, respectively), and the inward rectifier K(+) current (IK1) were inhibited by pioglitazone under conventional voltage clamp conditions. Ito was blocked significantly at concentrations ≥3 μM, ICa, IKr, IKs at concentrations ≥10 μM, while IK1 at concentrations ≥30 μM. Suppression of Ito, ICa, IKr, and IK1 has been confirmed also under action potential voltage clamp conditions. ATP-sensitive K(+) current, when activated by lemakalim, was effectively blocked by pioglitazone. Accordingly, action potentials were prolonged by 10 μM pioglitazone when the drug was applied in the presence of lemakalim. All these effects developed rapidly and were readily reversible upon washout. In conclusion, pioglitazone seems to be a harmless agent at usual therapeutic concentrations. Copyright © 2013 Elsevier B.V. All rights reserved.

Effects of hydrogen peroxide on voltage-dependent K+ currents in human cardiac fibroblasts through protein kinase pathways

PubMed Central

Bae, Hyemi; Lee, Donghee; Kim, Young-Won; Choi, Jeongyoon; Lee, Hong Jun; Kim, Sang-Wook; Kim, Taeho; Noh, Yun-Hee; Ko, Jae-Hong; Bang, Hyoweon

2016-01-01

Human cardiac fibroblasts (HCFs) have various voltage-dependent K+ channels (VDKCs) that can induce apoptosis. Hydrogen peroxide (H2O2) modulates VDKCs and induces oxidative stress, which is the main contributor to cardiac injury and cardiac remodeling. We investigated whether H2O2 could modulate VDKCs in HCFs and induce cell injury through this process. In whole-cell mode patch-clamp recordings, application of H2O2 stimulated Ca2+-activated K+ (KCa) currents but not delayed rectifier K+ or transient outward K+ currents, all of which are VDKCs. H2O2-stimulated KCa currents were blocked by iberiotoxin (IbTX, a large conductance KCa blocker). The H2O2-stimulating effect on large-conductance KCa (BKCa) currents was also blocked by KT5823 (a protein kinase G inhibitor) and 1 H-[1, 2, 4] oxadiazolo-[4, 3-a] quinoxalin-1-one (ODQ, a soluble guanylate cyclase inhibitor). In addition, 8-bromo-cyclic guanosine 3', 5'-monophosphate (8-Br-cGMP) stimulated BKCa currents. In contrast, KT5720 and H-89 (protein kinase A inhibitors) did not block the H2O2-stimulating effect on BKCa currents. Using RT-PCR and western blot analysis, three subtypes of KCa channels were detected in HCFs: BKCa channels, small-conductance KCa (SKCa) channels, and intermediate-conductance KCa (IKCa) channels. In the annexin V/propidium iodide assay, apoptotic changes in HCFs increased in response to H2O2, but IbTX decreased H2O2-induced apoptosis. These data suggest that among the VDKCs of HCFs, H2O2 only enhances BKCa currents through the protein kinase G pathway but not the protein kinase A pathway, and is involved in cell injury through BKCa channels. PMID:27162486

Volume-dependent ATP-conductive large-conductance anion channel as a pathway for swelling-induced ATP release.

PubMed

Sabirov, R Z; Dutta, A K; Okada, Y

2001-09-01

In mouse mammary C127i cells, during whole-cell clamp, osmotic cell swelling activated an anion channel current, when the phloretin-sensitive, volume-activated outwardly rectifying Cl(-) channel was eliminated. This current exhibited time-dependent inactivation at positive and negative voltages greater than around +/-25 mV. The whole-cell current was selective for anions and sensitive to Gd(3)+. In on-cell patches, single-channel events appeared with a lag period of approximately 15 min after a hypotonic challenge. Under isotonic conditions, cell-attached patches were silent, but patch excision led to activation of currents that consisted of multiple large-conductance unitary steps. The current displayed voltage- and time-dependent inactivation similar to that of whole-cell current. Voltage-dependent activation profile was bell-shaped with the maximum open probability at -20 to 0 mV. The channel in inside-out patches had the unitary conductance of approximately 400 pS, a linear current-voltage relationship, and anion selectivity. The outward (but not inward) single-channel conductance was suppressed by extracellular ATP with an IC(50) of 12.3 mM and an electric distance (delta) of 0.47, whereas the inward (but not outward) conductance was inhibited by intracellular ATP with an IC(50) of 12.9 mM and delta of 0.40. Despite the open channel block by ATP, the channel was ATP-conductive with P(ATP)/P(Cl) of 0.09. The single-channel activity was sensitive to Gd(3)+, SITS, and NPPB, but insensitive to phloretin, niflumic acid, and glibenclamide. The same pharmacological pattern was found in swelling-induced ATP release. Thus, it is concluded that the volume- and voltage-dependent ATP-conductive large-conductance anion channel serves as a conductive pathway for the swelling-induced ATP release in C127i cells.

Intrinsic spontaneous activity and subthreshold oscillations in neurones of the rat dorsal column nuclei in culture

PubMed Central

Reboreda, Antonio; Sánchez, Estela; Romero, Marcos; Lamas, J Antonio

2003-01-01

The basis of rhythmic activity observed at the dorsal column nuclei (DCN) is still open to debate. This study has investigated the electrophysiological properties of isolated DCN neurones deprived of any synaptic influence, using the perforated-patch technique. About half of the DCN neurones (64/130) were spontaneously active. More than half of the spontaneous neurones (36/64) showed a low threshold membrane oscillation (LTO) with a mean frequency of 11.4 Hz (range: 4.3–22.1 Hz, n = 20; I = 0). Cells showing LTOs also invariably showed a rhythmic 1.2 Hz clustering activity (groups of 2–5 action potentials separated by silent LTO periods). Also, more than one-third of the silent neurones presented clustering activity, always accompanied by LTOs, when slightly depolarised. The frequency of LTOs was voltage dependent and could be abolished by TTX (0.5 μM) and riluzole (30 μM), suggesting the participation of a sodium current. LTOs were also abolished by TEA (15 mM), which transformed clustering into tonic activity. In voltage clamp, most DCN neurones (85 %) showed a TTX-/riluzole-sensitive persistent sodium current (INa,p), which activated at about -60 mV and had a half-maximum activation at −49.8 mV. An M-like, non-inactivating outward current was present in 95 % of DCN neurones, and TEA (15 mM) inhibited this current by 73.7 %. The non-inactivating outward current was also inhibited by barium (1 mM) and linopirdine (10 μM), which suggests its M-like nature; both drugs failed to block the LTOs, but induced a reduction in their frequency by 56 and 20 %, respectively. These results demonstrate for the first time that DCN neurones have a complex and intrinsically driven clustering discharge pattern, accompanied by subthreshold membrane oscillations. Subthreshold oscillations rely on the interplay of a persistent sodium current and a non-inactivating TEA-sensitive outward current. PMID:12844503

Effects of Xinjining extract on inward rectifier potassium current in ventricular myocytes of guinea pig.

PubMed

Zhu, Ming-jun; Wang, Guo-juan; Wang, Yong-xia; Pu, Jie-lin; Liu, Hong-jun; Yu, Hai-bin

2010-02-01

To study the effect of Xinjining extract (, XJN) on inward rectifier potassium current (I(K1)) in ventricular myocyte (VMC) of guinea pigs and its anti-arrhythmic mechanism on ion channel level. Single VMC was enzymatically isolated by zymolisis, and whole-cell patch clamp recording technique was used to record the I(k1) in VMC irrigated with XJN of different concentrations (1.25, 2.50, 5.00 g/L; six samples for each). The stable current and conductance of the inward component of I(K1) as well as the outward component of peak I(K1) and conductance of it accordingly was recorded when the test voltage was set on -110 mV. The suppressive rate of XJN on the inward component of I(K1) was 9.54% + or - 5.81%, 34.82% + or - 15.03%, and 59.52% + or - 25.58% with a concentration of 1.25, 2.50, and 5.00 g/L, respectively, and that for the outward component of peak I(K1) was 23.94% + or - 7.45%, 52.98% + or - 19.62%, and 71.42% + or - 23.01%, respectively (all P<0.05). Moreover, different concentrations of XJN also showed effects for reducing I(K1) conductance. XJN has inhibitory effect on I(K1) in guinea pig's VMC, and that of the same concentration shows stronger inhibition on outward component than on inward component, which may be one of the mechanisms of its anti-arrhythmic effect.

Kv4.2 Knockout Mice Have Hippocampal-Dependent Learning and Memory Deficits

ERIC Educational Resources Information Center

Lugo, Joaquin N.; Brewster, Amy L.; Spencer, Corinne M.; Anderson, Anne E.

2012-01-01

Kv4.2 channels contribute to the transient, outward K[superscript +] current (A-type current) in hippocampal dendrites, and modulation of this current substantially alters dendritic excitability. Using Kv4.2 knockout (KO) mice, we examined the role of Kv4.2 in hippocampal-dependent learning and memory. We found that Kv4.2 KO mice showed a deficit…

Reconstruction of the action potential of ventricular myocardial fibres

PubMed Central

Beeler, G. W.; Reuter, H.

1977-01-01

1. A mathematical model of membrane action potentials of mammalian ventricular myocardial fibres is described. The reconstruction model is based as closely as possible on ionic currents which have been measured by the voltage-clamp method. 2. Four individual components of ionic current were formulated mathematically in terms of Hodgkin—Huxley type equations. The model incorporates two voltage- and time-dependent inward currents, the excitatory inward sodium current, iNa, and a secondary or slow inward current, is, primarily carried by calcium ions. A time-independent outward potassium current, iK1, exhibiting inward-going rectification, and a voltage- and time-dependent outward current, ix1, primarily carried by potassium ions, are further elements of the model. 3. The iNa is primarily responsible for the rapid upstroke of the action potential, while the other current components determine the configuration of the plateau of the action potential and the re-polarization phase. The relative importance of inactivation of is and of activation of ix1 for termination of the plateau is evaluated by the model. 4. Experimental phenomena like slow recovery of the sodium system from inactivation, frequency dependence of the action potential duration, all-or-nothing re-polarization, membrane oscillations are adequately described by the model. 5. Possible inadequacies and shortcomings of the model are discussed. PMID:874889

Activation of muscarinic M3 receptors inhibits large-conductance voltage- and Ca2+-activated K+ channels in rat urinary bladder smooth muscle cells

PubMed Central

Parajuli, Shankar P.

2013-01-01

Large conductance voltage- and Ca2+-activated K+ (BK) channels are key regulators of detrusor smooth muscle (DSM) contraction and relaxation during urine voiding and storage. Here, we explored whether BK channels are regulated by muscarinic receptors (M-Rs) in native freshly isolated rat DSM cells under physiological conditions using the perforated whole cell patch-clamp technique and pharmacological inhibitors. M-R activation with carbachol (1 μM) initially evoked large transient outward BK currents, followed by inhibition of the spontaneous transient outward BK currents (STBKCs) in DSM cells. Carbachol (1 μM) also inhibited the amplitude and frequency of spontaneous transient hyperpolarizations (STHs) and depolarized the DSM cell membrane potential. Selective inhibition of the muscarinic M3 receptors (M3-Rs) with 4-diphenylacetoxy-N-methylpiperidine (4-DAMP; 0.1 μM), but not muscarinic M2 receptors with methoctramine (1 μM), blocked the carbachol inhibitory effects on STBKCs. Furthermore, blocking the inositol 1,4,5-triphosphate (IP3) receptors with xestospongin-C (1 μM) inhibited the carbachol-induced large transient outward BK currents without affecting carbachol inhibitory effects on STBKCs. Upon pharmacological inhibition of all known cellular sources of Ca2+ for BK channel activation, carbachol (1 μM) did not affect the voltage-step-induced steady-state BK currents, suggesting that the muscarinic effects in DSM cells are mediated by mobilization of intracellular Ca2+. In conclusion, our findings provide strong evidence that activation of M3-Rs leads to inhibition of the STBKCs, STHs, and depolarization of DSM cells. Collectively, the data suggest the existence of functional interactions between BK channels and M3-Rs at a cellular level in DSM. PMID:23703523

Phospholipase C-independent effects of 3M3FBS in murine colon.

PubMed

Dwyer, Laura; Kim, Hyun Jin; Koh, Byoung Ho; Koh, Sang Don

2010-02-25

The muscarinic receptor subtype M(3) is coupled to Gq/11 proteins. Muscarinic receptor agonists such as carbachol stimulate these receptors that result in activation of phospholipase C (PLC) which hydrolyzes phosphatidylinositol 4,5-bisphosphate into diacylglycerol and Ins(1,4,5)P(3). This pathway leads to excitation and smooth muscle contraction. In this study the PLC agonist, 2, 4, 6-trimethyl-N-(meta-3-trifluoromethyl-phenyl)-benezenesulfonamide (m-3M3FBS), was used to investigate whether direct PLC activation mimics carbachol-induced excitation. We examined the effects of m-3M3FBS and 2, 4, 6-trimethyl-N-(ortho-3-trifluoromethyl-phenyl)-benzenesulfonamide (o-3M3FBS), on murine colonic smooth muscle tissue and cells by performing conventional microelectrode recordings, isometric force measurements and patch clamp experiments. Application of m-3M3FBS decreased spontaneous contractility in murine colonic smooth muscle without affecting the resting membrane potential. Patch clamp studies revealed that delayed rectifier K(+) channels were reversibly inhibited by m-3M3FBS and o-3M3FBS. The PLC inhibitor, 1-(6-((17b-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione (U73122), did not prevent this inhibition by m-3M3FBS. Both m-3M3FBS and o-3M3FBS decreased two components of delayed rectifier K(+) currents in the presence of tetraethylammonium chloride or 4-aminopyridine. Ca(2+) currents were significantly suppressed by m-3M3FBS and o-3M3FBS with a simultaneous increase in intracellular Ca(2+). Pretreatment with U73122 did not prevent the decrease in Ca(2+) currents upon m-3M3FBS application. In conclusion, both m-3M3FBS and o-3M3FBS inhibit inward and outward currents via mechanisms independent of PLC acting in an antagonistic manner. In contrast, both compounds also caused an increase in [Ca(2+)](i) in an agonistic manner. Therefore caution must be employed when interpreting their effects at the tissue and cellular level.

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

Molecular Coupling between Voltage Sensor and Pore Opening in the Arabidopsis Inward Rectifier K+ Channel KAT1

PubMed Central

Latorre, Ramon; Olcese, Riccardo; Basso, Claudia; Gonzalez, Carlos; Muñoz, Fabian; Cosmelli, Diego; Alvarez, Osvaldo

2003-01-01

Animal and plant voltage-gated ion channels share a common architecture. They are made up of four subunits and the positive charges on helical S4 segments of the protein in animal K+ channels are the main voltage-sensing elements. The KAT1 channel cloned from Arabidopsis thaliana, despite its structural similarity to animal outward rectifier K+ channels is, however, an inward rectifier. Here we detected KAT1-gating currents due to the existence of an intrinsic voltage sensor in this channel. The measured gating currents evoked in response to hyperpolarizing voltage steps consist of a very fast (τ = 318 ± 34 μs at −180 mV) and a slower component (4.5 ± 0.5 ms at −180 mV) representing charge moved when most channels are closed. The observed gating currents precede in time the ionic currents and they are measurable at voltages (less than or equal to −60) at which the channel open probability is negligible (≈10−4). These two observations, together with the fact that there is a delay in the onset of the ionic currents, indicate that gating charge transits between several closed states before the KAT1 channel opens. To gain insight into the molecular mechanisms that give rise to the gating currents and lead to channel opening, we probed external accessibility of S4 domain residues to methanethiosulfonate-ethyltrimethylammonium (MTSET) in both closed and open cysteine-substituted KAT1 channels. The results demonstrate that the putative voltage–sensing charges of S4 move inward when the KAT1 channels open. PMID:14517271

Geraniol blocks calcium and potassium channels in the mammalian myocardium: useful effects to treat arrhythmias.

PubMed

de Menezes-Filho, José Evaldo Rodrigues; Gondim, Antônio Nei Santana; Cruz, Jader Santos; de Souza, Américo Azevedo; Santos, José Nilson Andrade Dos; Conde-Garcia, Eduardo Antônio; de Sousa, Damião Pergentino; Santos, Michel Santana; de Oliveira, Evaleide Diniz; de Vasconcelos, Carla Maria Lins

2014-12-01

Geraniol is a monoterpene present in several essential oils, and it is known to have a plethora of pharmacological activities. In this study, we explored the contractile and electrophysiological properties of geraniol and its antiarrhythmic effects in the heart. The geraniol effects on atrial contractility, L-type Ca(2+) current, K(+) currents, action potential (AP) parameters, ECG profile and on the arrhythmia induced by ouabain were evaluated. In the atrium, geraniol reduced the contractile force (~98%, EC = 1,510 ± 160 μM) and diminished the positive inotropism of CaCl2 and BAY K8644. In cardiomyocytes, the IC a,L was reduced by 50.7% (n = 5) after perfusion with 300 μM geraniol. Moreover, geraniol prolonged the AP duration (APD) measured at 50% (n = 5) after repolarization, without changing the resting potential. The increased APD could be attributed to the blockade of the transient outward K(+) current (Ito ) (59.7%, n = 4), the non-inactivation K(+) current (Iss ) (39.2%, n = 4) and the inward rectifier K(+) current (IK 1 ) (33.7%, n = 4). In isolated hearts, geraniol increased PRi and QTi without affecting the QRS complex (n = 6), and it reduced both the left ventricular pressure (83%) and heart rate (16.5%). Geraniol delayed the time to onset of ouabain-induced arrhythmias by 128%, preventing 30% of the increase in resting tension (n = 6). Geraniol exerts its negative inotropic and chronotropic responses in the heart by decreasing both L-type Ca(2+) and voltage-gated K(+) currents, ultimately acting against ouabain-induced arrhythmias. © 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

The Extended Mind: Coupling Environment and Brain

NASA Astrophysics Data System (ADS)

Vrobel, Susie

2010-11-01

This paper describes embodiment and cognitive extension as examples of strong anticipation as defined by Dubois. Clark and Chalmers formulated a thesis which states that parts of the environment, if coupled successfully, can become part of the extended mind. This coupling, be it deliberate or unintentional, shifts the observer-world boundary outwards when the observer encompasses parts of his environment. The resulting extended observer forms a new systemic whole, which consists of both the assimilated context and the recalibrated version of the original observer. Recalibration occurs when conditioning and adaptation lead to corresponding changes on the neural level, for instance, when an agent compensates for delays in a control loop. Plasticity is a prerequisite for any successful incorporation of external structures. However, uncoupled parts of the observer must remain inviolate in order to preserve the boundary. Neither the extended mind nor the core observer are absolute concepts. Depending on whether we focus on local-scale interactions or on large-scale behaviour, boundaries are formed at different interfacial cuts, which lead to either an endo- or an exo-perspective or endo- or exo-anticipation, respectively. For biological extended agents which undergo a transition from exo- to endo-states, a tell-tale sign of a successful exo-endo transition is invisibility. This invisibility occurs when the agent is no longer aware of the delay originally introduced into the control loop by the assimilated part of the environment. Explaining the world in terms of effective causality is not sufficient to account for extended minds. The latter require explanations in terms of final causation. For extended minds, this ordering principle comes in the shape of nested hierarchical layers. The interfaces of these layers may have merged for an endo-observer, whereas an exo-observer can make out the detailed structure, including artificially introduced delays. A sufficient condition for an endo-observer to turn into an extended mind is the formation of a new systemic whole as a result of shifting the interfacial cut between exo-and endo-world outwards. However, this is only a necessary condition for an extended agent with strong anticipatory properties. It is invisibility which is a sufficient condition for strong or endo-anticipation.

Fluid flow plate for decreased density of fuel cell assembly

DOEpatents

Vitale, Nicholas G.

1999-01-01

A fluid flow plate includes first and second outward faces. Each of the outward faces has a flow channel thereon for carrying respective fluid. At least one of the fluids serves as reactant fluid for a fuel cell of a fuel cell assembly. One or more pockets are formed between the first and second outward faces for decreasing density of the fluid flow plate. A given flow channel can include one or more end sections and an intermediate section. An interposed member can be positioned between the outward faces at an interface between an intermediate section, of one of the outward faces, and an end section, of that outward face. The interposed member can serve to isolate the reactant fluid from the opposing outward face. The intermediate section(s) of flow channel(s) on an outward face are preferably formed as a folded expanse.

The changes of potassium currents in rabbit ventricle with healed myocardial infarction.

PubMed

Liu, Nian; Niu, Huiyan; Li, Yang; Zhang, Cuntai; Zhou, Qiang; Ruan, Yanfei; Pu, Jun; Lu, Zaiying

2004-01-01

To elucidate the mechanism of arrhythmia in healed myocardial infarction (HMI), the changes of action potential duration (APD), transient outward potassium current (Ito), delayed rectifier potassium current (IK) and inward rectifier potassium current (IK1) of left ventricular myocytes in non-infarcted zone of HMI were investigated. Rabbits were randomly assigned into two groups: HMI group, in which animals were subjected to thoracotomy and ligation of the circumflex coronary and sham-operated group, in which rabbits underwent thoracotomy but no conorary ligation. 3 months after the operation, the whole myocyte patch clamp technique was used to record APD, Ito, IK, and IK1 of ventricular myocytes in non-infarcted zone. Our results showed that the membrane capacitance was larger in HMI group than in sham-operated group. Action potential duration was significantly lengthened in HMI group and early afterdepolarization (EAD) appeared in HMI group. The densities of Ito, I(K, tail), and IK1 were reduced significantly in HMI group, from 6.72 +/- 0.42 pA/pF, 1.54 +/- 0.13 pA/pF and 25.6 +/- 2.6 pA/pF in sham-operated group to 4.03 +/- 0.33 pA/pF, 1.14 +/- 0.11 pA/pF and 17.6 +/- 2.3 pA/pF, respectively. It is concluded that the reduced densities of Ito, I(K, tail) and IK1 in ventricular myocytes of non-infarcted zone in HMI were responsible for the prolongation of APD and the presentation of EAD which played important roles in the development of malignant arrhythmia in HMI.

Present developments in theory of the solar wind

NASA Technical Reports Server (NTRS)

Parker, E. N.

1972-01-01

Current problems and developments in the theory of the large-scale expansion of the solar corona are reviewed. The outstanding question is whether the energy supply to the quiet corona is mainly thermal conduction outward from a region of active heating at its base, or mainly wave propagation outward from the base. It is suggested that the question can be settled only when the properties of the wind can be sampled over a wide range of radial distance from the sun, from far inside the orbit of earth to well beyond. It was suggested that hydromagnetic waves may drive the expansion of the active corona by direct transfer of momentum as well as energy.

Lightning Channel Corona Formation Treated as a Large System of Streamers

NASA Astrophysics Data System (ADS)

Carlson, B.; Lehtinen, N. G.; Kochkin, P.

2017-12-01

Transfer of charge along a lightning channel leads to strong electric fields that drive such charge outward. This charge flow is nonuniform, breaking up into millimeter-scale discharge structures called streamers. The motion of such streamers can carry charge many meters outward from the channel, but each individual streamer only carries a small amount of charge. Transfer of macroscopic charge outward thus requires a large population of streamers that are expected to interact and exhibit interesting collective behaviors. We attempt to simulate such collective behaviors by approximating the behavior of each streamer but retaining streamer interactions and overall electrodynamic effects and apply this simulation to a few key scenarios. For the case of flow of charge off a lightning channel, we simulate a continually growing population of streamers injected near a charged conducting channel. Further, motivated by lightning initiation, we simulate the growth of a population of streamers from a single seed streamer as might initiate from a hydrometeor. For all cases considered, we characterize the charges and currents involved, compare to observations where possible, and characterize the collective effects including spatial and temporal non-uniformity.

Radar Astrometry of Asteroid 99942 (2004 MN4): Predicting the 2029 Earth Encounter and Beyond

NASA Astrophysics Data System (ADS)

Giorgini, J. D.; Benner, L. A. M.; Nolan, M. C.; Ostro, S. J.

2005-08-01

Asteroid 2004 MN4 is expected to pass 4.6 (+/- 1.6) Earth-radii above the surface of the Earth on 2029-Apr-13. Such close approaches by objects as large as 2004 MN4 (D ≳ 0.3 km) are thought to occur at ≳ 1000-year intervals on average. 2004 MN4 is expected to reach 3rd magnitude and thus be visible to the unaided eye. With a disk 2-4 arcseconds across, it may be resolved by ground-based telescopes. Arecibo (2380-MHz) delay-Doppler radar astrometry, obtained in late January 2005, significantly corrected 2004 MN4's orbit by revealing a 1.4 arcsecond bias in pre-discovery optical measurements. Doppler-shifted echoes were acquired 4.8σ (176.4 mm/s) away from the predicted frequency on Jan 27. Range on Jan 29 was found to be 747 km (2.8σ ) closer to Earth than the pre-radar orbit predicted. Incorporation of these delay-Doppler measurements into a new weighted least-squares orbit solution moved the 2029-Apr-13 encounter prediction 5σ closer to the Earth, illustrating the problematic nature of prediction and statistical analysis with single-apparition optical data-sets. Without delay-Doppler data, the bias was not apparent, even when optical measurements spanned a full orbit period. The current combined data-set does not permit reliable trajectory propagation to encounters beyond 2029; Monte Carlo analysis shows that, by 2036, the 3σ confidence region wraps >300 degrees of heliocentric longitude around the Sun, with some sections of this statistical region experiencing low-probability encounters with the Earth in the 2030's, gravitationally scattering some possible trajectories inward to the orbit of Venus, or outward toward Mars. Future measurements from radar opportunities in August 2005 and May 2006 (SNR ≈5-10) have the potential to eliminate statistical encounters in the 2030's. Delay-Doppler astrometry from 2013 (SNR ≈30) should permit deterministic encounter prediction through 2070, shrinking the along-track uncertainty in 2036 by two orders of magnitude,from ≳ 8(10)8 km to ≲7(10)6 km.

Population of computational rabbit-specific ventricular action potential models for investigating sources of variability in cellular repolarisation.

PubMed

Gemmell, Philip; Burrage, Kevin; Rodriguez, Blanca; Quinn, T Alexander

2014-01-01

Variability is observed at all levels of cardiac electrophysiology. Yet, the underlying causes and importance of this variability are generally unknown, and difficult to investigate with current experimental techniques. The aim of the present study was to generate populations of computational ventricular action potential models that reproduce experimentally observed intercellular variability of repolarisation (represented by action potential duration) and to identify its potential causes. A systematic exploration of the effects of simultaneously varying the magnitude of six transmembrane current conductances (transient outward, rapid and slow delayed rectifier K(+), inward rectifying K(+), L-type Ca(2+), and Na(+)/K(+) pump currents) in two rabbit-specific ventricular action potential models (Shannon et al. and Mahajan et al.) at multiple cycle lengths (400, 600, 1,000 ms) was performed. This was accomplished with distributed computing software specialised for multi-dimensional parameter sweeps and grid execution. An initial population of 15,625 parameter sets was generated for both models at each cycle length. Action potential durations of these populations were compared to experimentally derived ranges for rabbit ventricular myocytes. 1,352 parameter sets for the Shannon model and 779 parameter sets for the Mahajan model yielded action potential duration within the experimental range, demonstrating that a wide array of ionic conductance values can be used to simulate a physiological rabbit ventricular action potential. Furthermore, by using clutter-based dimension reordering, a technique that allows visualisation of multi-dimensional spaces in two dimensions, the interaction of current conductances and their relative importance to the ventricular action potential at different cycle lengths were revealed. Overall, this work represents an important step towards a better understanding of the role that variability in current conductances may play in experimentally observed intercellular variability of rabbit ventricular action potential repolarisation.

Long-Term Fish Oil Supplementation Induces Cardiac Electrical Remodeling by Changing Channel Protein Expression in the Rabbit Model

PubMed Central

Xu, Xulin; Jiang, Min; Wang, Yuhong; Smith, Timothy; Baumgarten, Clive M.; Wood, Mark A.; Tseng, Gea-Ny

2010-01-01

Clinical trials and epidemiological studies have suggested that dietary fish oil (FO) supplementation can provide an anti-arrhythmic benefit in some patient populations. The underlying mechanisms are not entirely clear. We wanted to understand how FO supplementation (for 4 weeks) affected the action potential configuration/duration of ventricular myocytes, and the ionic mechanism(s)/molecular basis for these effects. The experiments were conducted on adult rabbits, a widely used animal model for cardiac electrophysiology and pathophysiology. We used gas chromatography - mass spectroscopy to confirm that FO feeding produced a marked increase in the content of n-3 polyunsaturated fatty acids in the phospholipids of rabbit hearts. Left ventricular myocytes were used in current and voltage clamp experiments to monitor action potentials and ionic currents, respectively. Action potentials of myocytes from FO-fed rabbits exhibited much more positive plateau voltages and prolonged durations. These changes could be explained by an increase in the L-type Ca current (ICaL) and a decrease in the transient outward current (Ito) in these myocytes. FO feeding did not change the delayed rectifier or inward rectifier current. Immunoblot experiments showed that the FO-feeding induced changes in ICaL and Ito were associated with corresponding changes in the protein levels of major pore-forming subunits of these channels: increase in Cav1.2 and decrease in Kv4.2 and Kv1.4. There was no change in other channel subunits (Cav1.1, Kv4.3, KChIP2, and ERG1). We conclude that long-term fish oil supplementation can impact on cardiac electrical activity at least partially by changing channel subunit expression in cardiac myocytes. PMID:20405051

Population of Computational Rabbit-Specific Ventricular Action Potential Models for Investigating Sources of Variability in Cellular Repolarisation

PubMed Central

Gemmell, Philip; Burrage, Kevin; Rodriguez, Blanca; Quinn, T. Alexander

2014-01-01

Variability is observed at all levels of cardiac electrophysiology. Yet, the underlying causes and importance of this variability are generally unknown, and difficult to investigate with current experimental techniques. The aim of the present study was to generate populations of computational ventricular action potential models that reproduce experimentally observed intercellular variability of repolarisation (represented by action potential duration) and to identify its potential causes. A systematic exploration of the effects of simultaneously varying the magnitude of six transmembrane current conductances (transient outward, rapid and slow delayed rectifier K+, inward rectifying K+, L-type Ca2+, and Na+/K+ pump currents) in two rabbit-specific ventricular action potential models (Shannon et al. and Mahajan et al.) at multiple cycle lengths (400, 600, 1,000 ms) was performed. This was accomplished with distributed computing software specialised for multi-dimensional parameter sweeps and grid execution. An initial population of 15,625 parameter sets was generated for both models at each cycle length. Action potential durations of these populations were compared to experimentally derived ranges for rabbit ventricular myocytes. 1,352 parameter sets for the Shannon model and 779 parameter sets for the Mahajan model yielded action potential duration within the experimental range, demonstrating that a wide array of ionic conductance values can be used to simulate a physiological rabbit ventricular action potential. Furthermore, by using clutter-based dimension reordering, a technique that allows visualisation of multi-dimensional spaces in two dimensions, the interaction of current conductances and their relative importance to the ventricular action potential at different cycle lengths were revealed. Overall, this work represents an important step towards a better understanding of the role that variability in current conductances may play in experimentally observed intercellular variability of rabbit ventricular action potential repolarisation. PMID:24587229

Functional changes in glutamate transporters and astrocyte biophysical properties in a rodent model of focal cortical dysplasia

PubMed Central

Campbell, Susan L.; Hablitz, John J.; Olsen, Michelle L.

2014-01-01

Cortical dysplasia is associated with intractable epilepsy and developmental delay in young children. Recent work with the rat freeze-induced focal cortical dysplasia (FCD) model has demonstrated that hyperexcitability in the dysplastic cortex is due in part to higher levels of extracellular glutamate. Astrocyte glutamate transporters play a pivotal role in cortical maintaining extracellular glutamate concentrations. Here we examined the function of astrocytic glutamate transporters in a FCD model in rats. Neocortical freeze lesions were made in postnatal day (PN) 1 rat pups and whole cell electrophysiological recordings and biochemical studies were performed at PN 21–28. Synaptically evoked glutamate transporter currents in astrocytes showed a near 10-fold reduction in amplitude compared to sham operated controls. Astrocyte glutamate transporter currents from lesioned animals were also significantly reduced when challenged exogenously applied glutamate. Reduced astrocytic glutamate transport clearance contributed to increased NMDA receptor-mediated current decay kinetics in lesioned animals. The electrophysiological profile of astrocytes in the lesion group was also markedly changed compared to sham operated animals. Control astrocytes demonstrate large-amplitude linear leak currents in response to voltage-steps whereas astrocytes in lesioned animals demonstrated significantly smaller voltage-activated inward and outward currents. Significant decreases in astrocyte resting membrane potential and increases in input resistance were observed in lesioned animals. However, Western blotting, immunohistochemistry and quantitative PCR demonstrated no differences in the expression of the astrocytic glutamate transporter GLT-1 in lesioned animals relative to controls. These data suggest that, in the absence of changes in protein or mRNA expression levels, functional changes in astrocytic glutamate transporters contribute to neuronal hyperexcitability in the FCD model. PMID:25565960

Involvement of Potassium and Cation Channels in Hippocampal Abnormalities of Embryonic Ts65Dn and Tc1 Trisomic Mice

PubMed Central

Stern, Shani; Segal, Menahem; Moses, Elisha

2015-01-01

Down syndrome (DS) mouse models exhibit cognitive deficits, and are used for studying the neuronal basis of DS pathology. To understand the differences in the physiology of DS model neurons, we used dissociated neuronal cultures from the hippocampi of Ts65Dn and Tc1 DS mice. Imaging of [Ca2+]i and whole cell patch clamp recordings were used to analyze network activity and single neuron properties, respectively. We found a decrease of ~ 30% in both fast (A-type) and slow (delayed rectifier) outward potassium currents. Depolarization of Ts65Dn and Tc1 cells produced fewer spikes than diploid cells. Their network bursts were smaller and slower than diploids, displaying a 40% reduction in Δf / f0 of the calcium signals, and a 30% reduction in propagation velocity. Additionally, Ts65Dn and Tc1 neurons exhibited changes in the action potential shape compared to diploid neurons, with an increase in the amplitude of the action potential, a lower threshold for spiking, and a sharp decrease of about 65% in the after-hyperpolarization amplitude. Numerical simulations reproduced the DS measured phenotype by variations in the conductance of the delayed rectifier and A-type, but necessitated also changes in inward rectifying and M-type potassium channels and in the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. We therefore conducted whole cell patch clamp measurements of M-type potassium currents, which showed a ~ 90% decrease in Ts65Dn neurons, while HCN measurements displayed an increase of ~ 65% in Ts65Dn cells. Quantitative real-time PCR analysis indicates overexpression of 40% of KCNJ15, an inward rectifying potassium channel, contributing to the increased inhibition. We thus find that changes in several types of potassium channels dominate the observed DS model phenotype. PMID:26501103

Activation of TRPC channels contributes to OA-NO2-induced responses in guinea-pig dorsal root ganglion neurons

PubMed Central

Zhang, Xiulin; Beckel, Jonathan M; Daugherty, Stephanie L; Wang, Ting; Woodcock, Stephen R; Freeman, Bruce A; de Groat, William C

2014-01-01

Effects of nitro-oleic acid (OA-NO2) on TRP channels were examined in guinea-pig dissociated dorsal root ganglia (DRG) neurons using calcium imaging and patch clamp techniques. OA-NO2 increased intracellular Ca2+ in 60–80% DRG neurons. 1-Oleoyl-2acetyl-sn-glycerol (OAG), a TRPC agonist, elicited responses in 36% of OA-NO2-sensitive neurons while capsaicin (TRPV1 agonist) or allyl-isothiocyanate (AITC, TRPA1 agonist) elicited responses in only 16% and 10%, respectively, of these neurons. A TRPV1 antagonist (diarylpiperazine, 5 μm) in combination with a TRPA1 antagonist (HC-030031, 30 μm) did not change the amplitude of the Ca2+ transients or percentage of neurons responding to OA-NO2; however, a reducing agent DTT (50 mm) or La3+ (50 μm) completely abolished OA-NO2 responses. OA-NO2 also induced a transient inward current associated with a membrane depolarization followed by a prolonged outward current and hyperpolarization in 80% of neurons. The reversal potentials of inward and outward currents were approximately −20 mV and −60 mV, respectively. Inward current was reduced when extracellular Na+ was absent, but unchanged by niflumic acid (100 μm), a Cl− channel blocker. Outward current was abolished in the absence of extracellular Ca2+ or a combination of two Ca2+-activated K+ channel blockers (iberiotoxin, 100 nm and apamin, 1 μm). BTP2 (1 or 10 μm), a broad spectrum TRPC antagonist, or La3+ (50 μm) completely abolished OA-NO2 currents. RT-PCR performed on mRNA extracted from DRGs revealed the expression of all seven subtypes of TRPC channels. These results support the hypothesis that OA-NO2 activates TRPC channels other than the TRPV1 and TRPA1 channels already known to be targets in rat and mouse sensory neurons and challenge the prevailing view that electrophilic compounds act specifically on TRPA1 or TRPV1 channels. The modulation of sensory neuron excitability via actions on multiple TRP channels can contribute to the anti-inflammatory effect of OA-NO2. PMID:25128576

Plasma circulation in Jupiter's magnetosphere

NASA Astrophysics Data System (ADS)

Chané, E.

2017-12-01

We are using our three-dimensional global MHD model of Jupiter's magnetosphere to study the plasma circulation in the magnetodisk. We show that the Iogenic plasma does not travel outward axisymmetrically but rather forms a long spiral arm of high density corotating with the planet. This leads to periodic phenomena in the magnetodisk: for instance, every rotation period, a region of high density is rapidly moving outward on the pre-noon sector. This leads to shearing motions that generate field aligned currents and periodically affect the main oval in this sector.We will also show how the interplanetary magnetic field influences the position of the magnetodisk in our simulations, displacing the current sheet above and below the equatorial plan. We will discuss how this is affecting the depleted flux-tubes returning from the night-side after unloading most of their plasma in the magnetotail (Vasyliunas cycle) and see how they can then move above or below the magnetodisk when arriving at dawn and then reconnect with the interplanetary magnetic field on the day-side.

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

Ahedo, Eduardo; Merino, Mario

A previous axisymmetric model of the supersonic expansion of a collisionless, hot plasma in a divergent magnetic nozzle is extended here in order to include electron-inertia effects. Up to dominant order on all components of the electron velocity, electron momentum equations still reduce to three conservation laws. Electron inertia leads to outward electron separation from the magnetic streamtubes. The progressive plasma filling of the adjacent vacuum region is consistent with electron-inertia being part of finite electron Larmor radius effects, which increase downstream and eventually demagnetize the plasma. Current ambipolarity is not fulfilled and ion separation can be either outwards ormore » inwards of magnetic streamtubes, depending on their magnetization. Electron separation penalizes slightly the plume efficiency and is larger for plasma beams injected with large pressure gradients. An alternative nonzero electron-inertia model [E. Hooper, J. Propul. Power 9, 757 (1993)] based on cold plasmas and current ambipolarity, which predicts inwards electron separation, is discussed critically. A possible competition of the gyroviscous force with electron-inertia effects is commented briefly.« less

Actions and mechanisms of action of novel analogues of sotalol on guinea-pig and rabbit ventricular cells.

PubMed Central

Connors, S. P.; Gill, E. W.; Terrar, D. A.

1992-01-01

1. The actions and mechanisms of action of novel analogues of sotalol which prolong cardiac action potentials were investigated in guinea-pig and rabbit isolated ventricular cells. 2. In guinea-pig and rabbit cells the compounds significantly prolonged action potential duration at 20% and 90% repolarization levels without affecting resting membrane potential. In guinea-pig but not rabbit cells there was an increase in action potential amplitude and in rabbit cells there was no change in the shape or position of the 'notch' in the action potential. 3. Possible mechanisms of action were studied in more detail in the case of compound II (1-(4-methanesulphonamidophenoxy)-3-(N-methyl 3,4 dichlorophenylethylamino)-2-propanol). Prolongation of action potential duration continued to occur in the presence of nisoldipine, and calcium currents recorded under voltage-clamp conditions were not reduced by compound II (1 microM). Action potential prolongation by compound II was also unaffected in the presence of 10 microM tetrodotoxin. 4. Compound II (1 microM) did not influence IK1 assessed from the current during ramp changes in membrane potential (20 mV s-1) over the range -90 to -10 mV. 5. Compound II (1 microM) blocked time-dependent delayed rectifier potassium current (IK) activated by step depolarizations and recorded as an outward tail following repolarization. When a submaximal concentration (50 nM) was applied there was no change in the apparent reversal potential of IK.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1393293

Therapeutic effects of a taurine-magnesium coordination compound on experimental models of type 2 short QT syndrome.

PubMed

An, Meng-Yao; Sun, Kai; Li, Yan; Pan, Ying-Ying; Yin, Yong-Qiang; Kang, Yi; Sun, Tao; Wu, Hong; Gao, Wei-Zhen; Lou, Jian-Shi

2018-03-01

Short QT syndrome (SQTS) is a genetic arrhythmogenic disease that can cause malignant arrhythmia and sudden cardiac death. The current therapies for SQTS have application restrictions. We previously found that Mg· (NH 2 CH 2 CH 2 SO 3 )2· H 2 O, a taurine-magnesium coordination compound (TMCC) exerted anti-arrhythmic effects with low toxicity. In this study we established 3 different models to assess the potential anti-arrhythmic effects of TMCC on type 2 short QT syndrome (SQT2). In Langendorff guinea pig-perfused hearts, perfusion of pinacidil (20 μmol/L) significantly shortened the QT interval and QTpeak and increased rTp-Te (P<0.05 vs control). Subsequently, perfusion of TMCC (1-4 mmol/L) dose-dependently increased the QT interval and QTpeak (P<0.01 vs pinacidil). TMCC perfusion also reversed the rTp-Te value to the normal range. In guinea pig ventricular myocytes, perfusion of trapidil (1 mmol/L) significantly shortened the action potential duration at 50% (APD 50 ) and 90% repolarization (APD 90 ), which was significantly reversed by TMCC (0.01-1 mmol/L, P<0.05 vs trapidil). In HEK293 cells that stably expressed the outward delayed rectifier potassium channels (I Ks ), perfusion of TMCC (0.01-1 mmol/L) dose-dependently inhibited the IKs current with an IC 50 value of 201.1 μmol/L. The present study provides evidence that TMCC can extend the repolarization period and inhibit the repolarizing current, I Ks , thereby representing a therapeutic candidate for ventricular arrhythmia in SQT2.

In vitro pharmacologic characterization of a cholinergic receptor on outer hair cells.

PubMed

Erostegui, C; Norris, C H; Bobbin, R P

1994-04-01

Acetylcholine (ACh) is the major neurotransmitter released from the efferent fibers in the cochlea onto the outer hair cells (OHCs). The type of ACh receptor on OHCs and the events subsequent to receptor activation are unclear. Therefore we studied the effect of agonists and antagonists of the ACh receptor on isolated OHCs from the guinea pig. OHCs were recorded from in whole cell voltage and current clamp configuration. ACh induced an increase in outward K+ current (IACh) which hyperpolarized the OHCs. No desensitization to ACh application was observed. Cs+ replaced K+ in carrying the IACh. The IACh is Ca(2+)-dependent, time and voltage sensitive, and different from the IKCa induced by depolarization of the membrane potential. When tested at 100 microM, several agonists also induced outward current responses (acetylcholine > suberyldicholine > or = carbachol > DMPP) whereas nicotine, cytisine and muscarine did not. The IACh response to 10 microM ACh was blocked by low concentrations of traditional and non-traditional-nicotinic antagonists (strychnine > curare > bicuculline > alpha-bungarotoxin > thimethaphan) and by higher concentrations of muscarinic antagonists (atropine > 4-DAMP > AF-DX 116 > pirenzepine). Pharmacologically, the ACh receptor on OHCs is nicotinic.

[Analysis of electrically evoked response (EER) in relation to the central visual pathway of the cat (1). Wave shape of the cat EER].

PubMed

Fukatsu, Y; Miyake, Y; Sugita, S; Saito, A; Watanabe, S

1990-11-01

To analyze the Electrically evoked response (EER) in relation to the central visual pathway, the authors studied the properties of wave patterns and peak latencies of EER in 35 anesthetized adult cats. The cat EER showed two early positive waves on outward current (cornea cathode) stimulus and three or four early positive waves on inward current (cornea anode) stimulus. These waves were recorded within 50 ms after stimulus onset, and were the most consistent components in cat EER. The stimulus threshold for EER showed a less individual variation than amplitude. The difference of stimulus threshold between outward and inward current stimulus was also essentially negligible. The stimulus threshold was higher in early components than in late components. The peak latency of EER became shorter and the amplitude became higher, as the stimulus intensity was increased. However, this tendency was reversed and some wavelets started to appear when the stimulus was extremely strong. The recording using short stimulus duration and bipolar electrodes enabled us to reduce the electrical artifact of EER. These results obtained from cats were compared with those of humans and rabbits.

Mechanism of block by tedisamil of transient outward current in human ventricular subepicardial myocytes

PubMed Central

Wettwer, Erich; Himmel, Herbert M; Amos, Gregory J; Li, Qi; Metzger, Franz; Ravens, Ursula

1998-01-01

Tedisamil is a new antiarrhythmic drug with predominant class III action. The aim of the present study was to investigate the blocking pattern of the compound on the transient outward current (Ito) in human subepicardial myocytes isolated from explanted left ventricles. Using the single electrode whole cell voltage clamp technique, Ito was analysed after appropriate voltage inactivation of sodium current and block of calcium current.Tedisamil reduced the amplitude of peak Ito, but did not affect the amplitude of non-inactivating outward current. The drug accelerated the apparent rate of Ito inactivation. The reduction in time constant of Ito inactivation depended on drug concentration, the apparent IC50 value was 4.4 μM.Tedisamil affected Ito amplitude in a use-dependent manner. After 2 min at −80 mV, maximum block of Ito was reached after 4–5 clamp steps either at the frequency of 0.2 or 2 Hz, indicating that the block was not frequency-dependent in an experimentally relevant range. Recovery from block was very slow and proceeded with a time constant of 12.1±1.8 s. Also in the presence of drug, a fraction of channels recovered from inactivation with a similar time constant as in control myocytes (i.e. 81±40 ms and 51±8 ms, respectively, n.s.).From the onset of fractional block of Ito by tedisamil during the initial 60 ms of a clamp step, we calculated k1=9×106 mol−1 s−1 for the association rate constant, and k2=23 s−1 for the dissociation rate constant. The resulting apparent KD was 2.6 μM and is similar to the IC50 value.The effects of tedisamil on Ito could be simulated by assuming a four state channel model where the drug binds to the channel in an open (activated) conformation. It is concluded that in human subepicardial myocytes tedisamil is an open channel blocker of Ito and that this effect probably contributes to the antiarrhythmic potential of this drug. PMID:9831899

Atrial-selective K+ channel blockers: potential antiarrhythmic drugs in atrial fibrillation?

PubMed

Ravens, Ursula

2017-11-01

In the wake of demographic change in Western countries, atrial fibrillation has reached an epidemiological scale, yet current strategies for drug treatment of the arrhythmia lack sufficient efficacy and safety. In search of novel medications, atrial-selective drugs that specifically target atrial over other cardiac functions have been developed. Here, I will address drugs acting on potassium (K + ) channels that are either predominantly expressed in atria or possess electrophysiological properties distinct in atria from ventricles. These channels include the ultra-rapidly activating, delayed outward-rectifying Kv1.5 channel conducting I Kur , the acetylcholine-activated inward-rectifying Kir3.1/Kir3.4 channel conducting I K,ACh , the Ca 2+ -activated K + channels of small conductance (SK) conducting I SK , and the two-pore domain K + (K2P) channels (tandem of P domains, weak inward-rectifying K + channels (TWIK-1), TWIK-related acid-sensitive K + channels (TASK-1 and TASK-3)) that are responsible for voltage-independent background currents I TWIK-1 , I TASK-1 , and I TASK-3 . Direct drug effects on these channels are described and their putative value in treatment of atrial fibrillation is discussed. Although many potential drug targets have emerged in the process of unravelling details of the pathophysiological mechanisms responsible for atrial fibrillation, we do not know whether novel antiarrhythmic drugs will be more successful when modulating many targets or a single specific one. The answer to this riddle can only be solved in a clinical context.

The Year Abroad: Understanding the Employability Skills of the Global Graduate

ERIC Educational Resources Information Center

López-Moreno, Cristina

2017-01-01

This chapter will examine the employability profile of outwardly mobile British graduates and the ways in which their international skillset fits the UK labour market. It will draw upon several recent reports to highlight the current shortage of professionals with such global skills. In this context, the chapter will demonstrate that…

Northwest Outward Bound Instructor's Manual.

ERIC Educational Resources Information Center

Northwest Outward Bound School, Portland, OR.

Instructor responsibilities, procedures for completing activities safely, and instructional methods and techniques are outlined to assist instructors in the Northwest Outward Bound School (Portland, Oregon) as they strive for teaching excellence. Information is organized into six chapters addressing: history and philosophy of Outward Bound; course…

Parasitic momentum flux in the tokamak core

DOE PAGES

Stoltzfus-Dueck, T.

2017-03-06

A geometrical correction to the E × B drift causes an outward flux of co-current momentum whenever electrostatic potential energy is transferred to ion parallel flows. The robust, fully nonlinear symmetry breaking follows from the free-energy flow in phase space and does not depend on any assumed linear eigenmode structure. The resulting rotation peaking is counter-current and scales as temperature over plasma current. Lastly, this peaking mechanism can only act when fluctuations are low-frequency enough to excite ion parallel flows, which may explain some recent experimental observations related to rotation reversals.

Outward-dipping ring-fault structure at rabaul caldera as shown by earthquake locations.

PubMed

Mori, J; McKee, C

1987-01-09

The locations of a large number of earthquakes recorded at Rabaul caldera in Papua New Guinea from late 1983 to mid-1985 have produced a picture of this active caldera's structural boundary. The earthquake epicenters form an elliptical annulus about 10 kilometers long by 4 kilometers wide, centered in the southern part of the Rabaul volcanic complex. A set of events with well-constrained depth determinations shows a ring-fault structure that extends from the surface to a depth of about 4 kilometers and slopes steeply outward from the center of the caldera. This is the first geophysical data set that clearly outlines the orientation of an active caldera's bounding faults. This orientation, however, conflicts with the configuration of many other calderas and is not in keeping with currently preferred models of caldera formation.

Gradual Streamer Expansions and the Relationship between Blobs and Inflows

NASA Astrophysics Data System (ADS)

Wang, Y.-M.; Hess, P.

2018-06-01

Coronal helmet streamers show a continual tendency to expand outward and pinch off, giving rise to flux ropes that are observed in white light as “blobs” propagating outward along the heliospheric current/plasma sheet. The blobs form within the r ∼ 2–6 R ⊙ heliocentric range of the Large Angle and Spectrometric Coronagraph (LASCO) C2 instrument, but the expected inward-moving counterparts are often not detected. Here we show that the height of blob formation varies as a function of the underlying photospheric field, with the helmet streamer loops expanding to greater heights when active regions (ARs) emerge underneath them. When the pinch-offs occur at r ∼ 3–4 R ⊙, diverging inward/outward tracks sometimes appear in height–time maps constructed from LASCO C2 running-difference images. When the underlying photospheric field is weak, the blobs form closer to the inner edge of the C2 field of view and only the outward tracks are clearly visible. Conversely, when the emergence of large ARs leads to a strengthening of the outer coronal field and an increase in the total white-light radiance (as during late 2014), the expanding helmet-streamer loops pinch off beyond r ∼ 4 R ⊙, triggering strong inflow streams whose outgoing counterparts are usually very faint. We deduce that the visibility of the blobs and inflows depends on the amount of material that the diverging components sweep up within the 2–6 R ⊙ field of view. We also note that the rate of blob production tends to increase when a helmet streamer is “activated” by underlying flux emergence.

Laboratory experiment on the 3D tide-induced Lagrangian residual current using the PIV technique

NASA Astrophysics Data System (ADS)

Chen, Yang; Jiang, Wensheng; Chen, Xu; Wang, Tao; Bian, Changwei

2017-12-01

The 3D structure of the tide-induced Lagrangian residual current was studied using the particle image velocimetry (PIV) technique in a long shallow narrow tank in the laboratory. At the mouth of the tank, a wave generator was used to make periodic wave which represents the tide movement, and at the head of the tank, a laterally sloping topography with the length of one fifth of the water tank was installed, above which the tide-induced Lagrangian residual current was studied. Under the weakly nonlinear condition in the present experiment setup, the results show that the Lagrangian residual velocity (LRV) field has a three-layer structure. The residual current flows inwards (towards the head) in the bottom layer and flows outwards in the middle layer, while in the surface layer, it flows inwards along the shallow side of the sloping topography and outwards along the deep side. The depth-averaged and breadth-averaged LRV are also analyzed based on the 3D LRV observations. Our results are in good agreement with the previous experiment studies, the analytical solutions with similar conditions and the observational results in real bays. Moreover, the volume flux comparison between the Lagrangian and Eulerian residual currents shows that the Eulerian residual velocity violates the mass conservation law while the LRV truly represents the inter-tidal water transport. This work enriches the laboratory studies of the LRV and offers valuable references for the LRV studies in real bays.

Mechanisms of the palmitoylcarnitine-induced response in vascular endothelial cells.

PubMed

Taki, H; Muraki, K; Imaizumi, Y; Watanabe, M

1999-09-01

The mechanisms of Ca2+ mobilization induced by palmitoylcarnitine (Palcar) in rabbit aortic endothelial cells (ETCs) were examined using electrophysiological techniques. The results obtained were compared with those induced by acetylcholine (ACh). When a rabbit aortic muscle preparation with an intact endothelium was treated with 10 microM Palcar, the ACh-induced relaxation was markedly attenuated, whereas endothelium-independent relaxation caused by sodium nitroprusside was not affected. Under perforated-patch whole-cell-clamp conditions, the application of Palcar over the concentration range 0.3 and 10 microM elicited a slowly activating outward current (IPalcar-out), whereas ACh induced a rapidly activating outward current (IACh). A potassium channel blocker, 4-aminopyridine, significantly inhibited both IPalcar-out and IACh. Removal of external Ca2+ almost abolished IPalcar-out. Under the same conditions, however, IACh remained transient. Addition of cation channel blockers SK&F96365 and La3+ inhibited IPalcar-out more effectively than IACh. Application of staurosporine, an inhibitor of protein kinase C, affected neither IACh nor IPalcar-out. In contrast, treatment of ETCs with pertussis toxin (PTX) reduced IACh and almost abolished IPalcar-out. These findings demonstrate that, in ETCs, Palcar induces Ca2+ influx via the activation of PTX-sensitive GTP-binding protein, leading to the activation of Ca(2+)-dependent K+ current and hyperpolarization of the cell.

Substorms At Jupiter: Galileo Observations of Transient Reconnection in The Near Tail

NASA Technical Reports Server (NTRS)

Russell, C. T.; Khurana, K. K.; Kivelson, M. G.; Huddleston, D. E.

2000-01-01

The magnetic flux content of the Jovian magnetosphere is set by the internal dynamo, but those magnetic field lines are constantly being loaded by heavy ions at the orbit of lo and dragged inexorably outward by the centrifugal force. Vasyliunas has proposed a steady state reconnecting magnetospheric model that sheds plasma islands of zero net magnetic flux and returns nearly empty flux tubes to the inner magnetosphere. The Galileo observations indicate that beyond 40 Rj the current sheet begins to tear and beyond 50 Rj on the nightside explosively reconnects as the tearing site reaches the low density lobe region above and below the current sheet. Small events occur irregularly but on average about every 4 hours and large events about once a day. The magnetic flux reconnected in such events amounts up to about 70,000 Webers/sec and is sufficient to return the outwardly convected magnetic flux to the inner magnetosphere. Since this process releases plasmoids into the jovian tail, as do terrestrial substorms; since this process involves explosive reconnection across the current sheet on the nightside of the planet, as do terrestrial substorms; and since the process is a key in closing the circulation pattern of the magnetic and plasma flux, as it is in terrestrial substorms; we refer to these events as jovian substorms.

Neuromedin U Type 1 Receptor Stimulation of A-type K+ Current Requires the βγ Subunits of Go Protein, Protein Kinase A, and Extracellular Signal-regulated Kinase 1/2 (ERK1/2) in Sensory Neurons*

PubMed Central

Zhang, Yiming; Jiang, Dongsheng; Zhang, Yuan; Jiang, Xinghong; Wang, Fen; Tao, Jin

2012-01-01

Although neuromedin U (NMU) has been implicated in analgesia, the detailed mechanisms still remain unclear. In this study, we identify a novel functional role of NMU type 1 receptor (NMUR1) in regulating the transient outward K+ currents (IA) in small dorsal root ganglion (DRG) neurons. We found that NMU reversibly increased IA in a dose-dependent manner, instead the sustained delayed rectifier K+ current (IDR) was not affected. This NMU-induced IA increase was pertussis toxin-sensitive and was totally reversed by NMUR1 knockdown. Intracellular application of GDPβS (guanosine 5′-O-(2-thiodiphosphate)), QEHA peptide, or a selective antibody raised against the Gαo or Gβ blocked the stimulatory effects of NMU. Pretreatment of the cells with the protein kinase A (PKA) inhibitor or ERK inhibitor abolished the NMU-induced IA response, whereas inhibition of phosphatidylinositol 3-kinase or PKC had no such effects. Exposure of DRG neurons to NMU markedly induced the phosphorylation of ERK (p-ERK), whereas p-JNK or p-p38 was not affected. Moreover, the NMU-induced p-ERK increase was attenuated by PKA inhibition and activation of PKA by foskolin would mimic the NMU-induced IA increase. Functionally, we observed a significant decrease of the firing rate of neuronal action potential induced by NMU and pretreatment of DRG neurons with 4-AP could abolish this effect. In summary, these results suggested that NMU increases IA via activation of NMUR1 that couples sequentially to the downstream activities of Gβγ of the Go protein, PKA, and ERK, which could contribute to its physiological functions including neuronal hypoexcitability in DRG neurons. PMID:22493291

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

Outward Bound--An Adjunctive Psychiatric Therapy: Preliminary Research Findings.

ERIC Educational Resources Information Center

Stich, Thomas F.; Sussman, Lewis R.

According to a small study, Outward Bound can enhance the treatment of hospitalized psychiatric patients. Researchers measured the effect of a therapeutic Outward Bound program of prescribed physical and social tasks on the contentment and self-esteem of seven patients undergoing short-term treatment at the Veterans Administration Hospital in…

Innovative Adolescent Chemical Dependency Treatment and Its Outcome: A Model Based on Outward Bound Programming.

ERIC Educational Resources Information Center

McPeake, John D.; And Others

1991-01-01

Describes adolescent chemical dependency treatment model developed at Beech Hill Hospital (New Hampshire) which integrated Twelve Step-oriented alcohol and drug rehabilitation program with experiential education school, Hurricane Island Outward Bound School. Describes Beech Hill Hurricane Island Outward Bound School Adolescent Chemical Dependency…

Closed Classrooms, High Mountains and Strange Lands: An Inquiry into Culture and Caring.

ERIC Educational Resources Information Center

Kraft, Richard J.

1992-01-01

The current closed classroom system of education is not sufficient in preparing students for real world life. Proposes that the wilderness, cross-cultural, and international settings are a very powerful learning environment in which life-changing experiences can and do occur. Presents the Outward Bound process and Adler's stage theory of…

Changes in left ventricular repolarization and ion channel currents following a transient rate increase superimposed on bradycardia in anesthetized dogs.

PubMed

Rubart, M; Lopshire, J C; Fineberg, N S; Zipes, D P

2000-06-01

We previously demonstrated in dogs that a transient rate increase superimposed on bradycardia causes prolongation of ventricular refractoriness that persists for hours after resumption of bradycardia. In this study, we examined changes in membrane currents that are associated with this phenomenon. The whole cell, patch clamp technique was used to record transmembrane voltages and currents, respectively, in single mid-myocardial left ventricular myocytes from dogs with 1 week of complete AV block; dogs either underwent 1 hour of left ventricular pacing at 120 beats/min or did not undergo pacing. Pacing significantly heightened mean phase 1 and peak plateau amplitudes by approximately 6 and approximately 3 mV, respectively (P < 0.02), and prolonged action potential duration at 90% repolarization from 235+/-8 msec to 278+/-8 msec (1 Hz; P = 0.02). Rapid pacing-induced changes in transmembrane ionic currents included (1) a more pronounced cumulative inactivation of the 4-aminopyridine-sensitive transient outward K+ current, Ito, over the range of physiologic frequencies, resulting from a approximately 30% decrease in the population of quickly reactivating channels; (2) increases in peak density of L-type Ca2+ currents, I(Ca.L), by 15% to 35 % between +10 and +60 mV; and (3) increases in peak density of the Ca2+-activated chloride current, I(Cl.Ca), by 30% to 120% between +30 and +50 mV. Frequency-dependent reduction in Ito combined with enhanced I(Ca.L) causes an increase in net inward current that may be responsible for the observed changes in ventricular repolarization. This augmentation of net cation influx is partially antagonized by an increase in outward I(Ca.Cl).

Ca2+ current of frog vestibular hair cells is modulated by intracellular ATP but not by long-lasting depolarisation.

PubMed

Martini, Marta; Farinelli, Federica; Rossi, Maria Lisa; Rispoli, Giorgio

2007-09-01

Some aspects of Ca(2+) channel modulation in hair cells isolated from semicircular canals of the frog (Rana esculenta) have been investigated using the whole-cell technique and intra and extracellular solutions designed to modify the basic properties of the Ca(2+) macrocurrent. With 1 mM ATP in the pipette solution, about 60% of the recorded cells displayed a Ca(2+) current constituted by a mix of an L and a drug-resistant (R2) component; the remaining 40% exhibited an additional drug-resistant fraction (R1), which inactivated in a Ca-dependent manner. If the pipette ATP was raised to 10 mM, cells exhibiting the R1 current fraction displayed an increase of both the R1 and L components by approximately 280 and approximately 70%, respectively, while cells initially lacking R1 showed a similar increase in the L component with R1 becoming apparent and raising up to a mean amplitude of approximately 44 pA. In both cell types the R2 current fraction was negligibly affect by ATP. The current run-up was unaffected by cyclic nucleotides, and was not triggered by 10 mM ATPgammaS, ADP, AMP or GTP. Long-lasting depolarisations (>5 s) produced a progressive, reversible decay in the inward current despite the presence of intracellular ATP. Ca(2+) channel blockade by Cd(2+) unmasked a slowly activating outward Cs(+) current flowing through a non-Ca(2+) channel type, which became progressively unblocked by prolonged depolarisation even though Cs(+) and TEA(+) were present on both sides of the channel. The outward current waveform could be erroneously ascribed to a Ca- and/or voltage dependence of the Ca(2+) macrocurrent.

Calcium Homeostasis Modulator 1-Like Currents in Rat Fungiform Taste Cells Expressing Amiloride-Sensitive Sodium Currents.

PubMed

Bigiani, Albertino

2017-05-01

Salt reception by taste cells is still the less understood transduction process occurring in taste buds, the peripheral sensory organs for the detection of food chemicals. Although there is evidence suggesting that the epithelial sodium channel (ENaC) works as sodium receptor, yet it is not clear how salt-detecting cells signal the relevant information to nerve endings. Taste cells responding to sweet, bitter, and umami substances release ATP as neurotransmitter through a nonvesicular mechanism. Three different channel proteins have been proposed as conduit for ATP secretion: pannexin channels, connexin hemichannels, and calcium homeostasis modulator 1 (CALHM1) channels. In heterologous expression systems, these channels mediate outwardly rectifying membrane currents with distinct biophysical and pharmacological properties. I therefore tested whether also salt-detecting taste cells were endowed with these currents. To this aim, I applied the patch-clamp techniques to single cells in isolated taste buds from rat fungiform papillae. Salt-detecting cells were functionally identified by exploiting the effect of amiloride, which induces a current response by shutting down ENaCs. I looked for the presence of outwardly rectifying currents by using appropriate voltage-clamp protocols and specific pharmacological tools. I found that indeed salt-detecting cells possessed these currents with properties consistent with the presence, at least in part, of CALHM1 channels. Unexpectedly, CALHM1-like currents in taste cells were potentiated by known blockers of pannexin, suggesting a possible inhibitory action of this protein on CALMH1. These findings indicate that communication between salt-detecting cells and nerve endings might involve ATP release by CALMH1 channels. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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

Biophysical mechanism of spike threshold dependence on the rate of rise of the membrane potential by sodium channel inactivation or subthreshold axonal potassium current

PubMed Central

Wester, Jason C.

2013-01-01

Spike threshold filters incoming inputs and thus gates activity flow through neuronal networks. Threshold is variable, and in many types of neurons there is a relationship between the threshold voltage and the rate of rise of the membrane potential (dVm/dt) leading to the spike. In primary sensory cortex this relationship enhances the sensitivity of neurons to a particular stimulus feature. While Na+ channel inactivation may contribute to this relationship, recent evidence indicates that K+ currents located in the spike initiation zone are crucial. Here we used a simple Hodgkin-Huxley biophysical model to systematically investigate the role of K+ and Na+ current parameters (activation voltages and kinetics) in regulating spike threshold as a function of dVm/dt. Threshold was determined empirically and not estimated from the shape of the Vm prior to a spike. This allowed us to investigate intrinsic currents and values of gating variables at the precise voltage threshold. We found that Na+ inactivation is sufficient to produce the relationship provided it occurs at hyperpolarized voltages combined with slow kinetics. Alternatively, hyperpolarization of the K+ current activation voltage, even in the absence of Na+ inactivation, is also sufficient to produce the relationship. This hyperpolarized shift of K+ activation allows an outward current prior to spike initiation to antagonize the Na+ inward current such that it becomes self-sustaining at a more depolarized voltage. Our simulations demonstrate parameter constraints on Na+ inactivation and the biophysical mechanism by which an outward current regulates spike threshold as a function of dVm/dt. PMID:23344915

Rivaroxaban modulates electrical and mechanical characteristics of left atrium

PubMed Central

2013-01-01

Background Rivaroxaban reduces stroke in patients with atrial fibrillation (AF). Left atrium (LA) plays a critical role in the pathophysiology of AF. However, the electromechanical effects of rivaroxaban on LA are not clear. Results Conventional microelectrodes and a whole-cell patch-clamp were used to record the action potentials (APs) and ionic currents in rabbit LA preparations and isolated single LA cardiomyocytes before and after the administration of rivaroxaban. Rivaroxaban (10, 30, 100, and 300 nM) concentration-dependently reduced LA (n = 7) AP durations at 90% repolarization (APD90) from 76 ± 2 to 79 ± 3, 67 ± 4 (P < 0.05, vs. control), 59 ± 5, (P < 0.01, vs. control), and 56 ± 4 ms (P < 0.005, vs. control), respectively. Rivaroxaban (10, 30, 100, and 300 nM) concentration-dependently increased the LA (n = 7) diastolic tension by 351 ± 69 (P < 0.05, vs. control), 563 ± 136 (P < 0.05, vs. control), 582 ± 119 (P < 0.05, vs. control), and 603 ± 108 mg (P < 0.005, vs. control), respectively, but did not change LA contractility. In the presence of L-NAME (100 μM) and indomethacin (10 μM), additional rivaroxaban (300 nM) treatment did not significantly further increase the LA (n = 7) diastolic tension, but shortened the APD90 from 73 ± 2 to 60 ± 6 ms (P < 0.05, vs. control). Rivaroxaban (100 nM) increased the L-type calcium current and ultra-rapid delayed rectifier potassium current, but did not change the transient outward potassium current in isolated LA cardiomyocytes. Conclusions Rivaroxaban modulates LA electrical and mechanical characteristics with direct ionic current effects. PMID:23497194

Modulation of intracellular Ca2+ via L-type calcium channels in heart cells by the autoantibody directed against the second extracellular loop of the alpha1-adrenoceptors.

PubMed

Bkaily, Ghassan; El-Bizri, Nesrine; Bui, Michel; Sukarieh, Rami; Jacques, Danielle; Fu, Michael L X

2003-03-01

The effects of methoxamine, a selective alpha1-adrenergic receptor agonist, and the autoantibody directed against the second extracellular loop of alpha1-adrenoceptors were studied on intracellular free Ca2+ levels using confocal microscopy and ionic currents using the whole-cell patch clamp technique in single cells of 10-day-old embryonic chick and 20-week-old fetal human hearts. We observed that like methoxamine, the autoantibody directed against the second extracellular loop of alpha1-adrenoreceptors significantly increased the L-type calcium current (I(Ca(L))) but had no effect on the T-type calcium current (I(Ca(T))), the delayed outward potassium current, or the fast sodium current. This effect of the autoantibody was prevented by a prestimulation of the receptors with methoxamine and vice versa. Moreover, treating the cells with prazosin, a selective alpha1-adrenergic receptor antagonist blocked the methoxamine and the autoantibody-induced increase in I(Ca(L)), respectively. In absence of prazosin, both methoxamine and the autoantibody showed a substantial enhancement in the frequency of cell contraction and that of the concomitant cytosolic and nuclear free Ca2+ variations. The subsequent addition of nifedipine, a specific L-type Ca2+ channel blocker, reversed not only the methoxamine or the autoantibody-induced effect but also completely abolished cell contraction. These results demonstrated that functional alpha1-adrenoceptors exist in both 10-day-old embryonic chick and 20-week-old human fetal hearts and that the autoantibody directed against the second extracellular loop of this type of receptors plays an important role in stimulating their activity via activation of L-type calcium channels. This loop seems to have a functional significance by being the target of alpha1-receptor agonists like methoxamine.

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.

Role of Nrf2 in preventing oxidative stress induced chloride current alteration in human lung cells.

PubMed

Canella, Rita; Benedusi, Mascia; Martini, Marta; Cervellati, Franco; Cavicchio, Carlotta; Valacchi, Giuseppe

2018-08-01

The lung tissue is one of the main targets of oxidative stress due to external sources and respiratory activity. In our previous work, we have demonstrated in that O 3 exposure alters the Cl - current-voltage relationship, with the appearance of a large outward rectifier component mainly sustained by outward rectifier chloride channels (ORCCs) in human lung epithelial cells (A549 line). In the present study, we have performed patch clamp experiments, in order to identify which one of the O 3 byproducts (4hydroxynonenal (HNE) and/or H 2 O 2 ) was responsible for chloride current change. While 4HNE exposition (up to 25 μM for 30' before electrophysiological analysis) did not reproduce O 3 effect, H 2 O 2 produced by glucose oxidase 10 mU for 24 hr before electrophysiological analysis mimicked O 3 response. This result was confirmed treating the cell with catalase (CAT) before O 3 exposure (1,000 U/ml for 2 hr): CAT was able to rescue Cl - current alteration. Since CAT is regulated by Nrf2 transcription factor, we pre-treated the cells with the Nrf2 activators, resveratrol and tBHQ. Immunochemical and immunocytochemical results showed Nrf2 activation with both substances that lead to prevent OS effect on Cl - current. These data bring new insights into the mechanisms involved in OS-induced lung tissue damage, pointing out the role of H 2 O 2 in chloride current alteration and the ability of Nfr2 activation in preventing this effect. © 2017 Wiley Periodicals, Inc.

Airway epithelial wounds in rhesus monkey generate ionic currents that guide cell migration to promote healing

PubMed Central

Sun, Yao-Hui; Reid, Brian; Fontaine, Justin H.; Miller, Lisa A.; Hyde, Dallas M.; Mogilner, Alex

2011-01-01

Damage to the respiratory epithelium is one of the most critical steps to many life-threatening diseases, such as acute respiratory distress syndrome and chronic obstructive pulmonary disease. The mechanisms underlying repair of the damaged epithelium have not yet been fully elucidated. Here we provide experimental evidence suggesting a novel mechanism for wound repair: endogenous electric currents. It is known that the airway epithelium maintains a voltage difference referred to as the transepithelial potential. Using a noninvasive vibrating probe, we demonstrate that wounds in the epithelium of trachea from rhesus monkeys generate significant outward electric currents. A small slit wound produced an outward current (1.59 μA/cm2), which could be enhanced (nearly doubled) by the ion transport stimulator aminophylline. In addition, inhibiting cystic fibrosis transmembrane conductance regulator (CFTR) with CFTR(Inh)-172 significantly reduced wound currents (0.17 μA/cm2), implicating an important role of ion transporters in wound induced electric potentials. Time-lapse video microscopy showed that applied electric fields (EFs) induced robust directional migration of primary tracheobronchial epithelial cells from rhesus monkeys, towards the cathode, with a threshold of <23 mV/mm. Reversal of the field polarity induced cell migration towards the new cathode. We further demonstrate that application of an EF promoted wound healing in a monolayer wound healing assay. Our results suggest that endogenous electric currents at sites of tracheal epithelial injury may direct cell migration, which could benefit restitution of damaged airway mucosa. Manipulation of ion transport may lead to novel therapeutic approaches to repair damaged respiratory epithelium. PMID:21719726

Effect of electrical coupling on ionic current and synaptic potential measurements.

PubMed

Rabbah, Pascale; Golowasch, Jorge; Nadim, Farzan

2005-07-01

Recent studies have found electrical coupling to be more ubiquitous than previously thought, and coupling through gap junctions is known to play a crucial role in neuronal function and network output. In particular, current spread through gap junctions may affect the activation of voltage-dependent conductances as well as chemical synaptic release. Using voltage-clamp recordings of two strongly electrically coupled neurons of the lobster stomatogastric ganglion and conductance-based models of these neurons, we identified effects of electrical coupling on the measurement of leak and voltage-gated outward currents, as well as synaptic potentials. Experimental measurements showed that both leak and voltage-gated outward currents are recruited by gap junctions from neurons coupled to the clamped cell. Nevertheless, in spite of the strong coupling between these neurons, the errors made in estimating voltage-gated conductance parameters were relatively minor (<10%). Thus in many cases isolation of coupled neurons may not be required if a small degree of measurement error of the voltage-gated currents or the synaptic potentials is acceptable. Modeling results show, however, that such errors may be as high as 20% if the gap-junction position is near the recording site or as high as 90% when measuring smaller voltage-gated ionic currents. Paradoxically, improved space clamp increases the errors arising from electrical coupling because voltage control across gap junctions is poor for even the highest realistic coupling conductances. Furthermore, the common procedure of leak subtraction can add an extra error to the conductance measurement, the sign of which depends on the maximal conductance.

Insulin stimulation of rat ventricular K+ currents depends on the integrity of the cytoskeleton.

PubMed

Shimoni, Y; Ewart, H S; Severson, D

1999-02-01

1. The effect of insulin on K+ currents was studied with enzymatically dispersed ventricular myocytes from insulin-deficient (type I) diabetic rats. Diabetic conditions were induced by a single intravenous injection of streptozotocin (100 mg kg-1) given 8-13 days before the experiments. Measurements of plasma glucose and insulin levels confirmed the diabetic status of the animals. 2. A Ca2+-independent transient outward K+ current, It, and a slowly inactivating, quasi-steady-state current, Iss, which are depressed in diabetic myocytes, could be restored by exposure to 1, 10 or 100 nM insulin. This was only observed after a delay of 5-6 h, although an insulin exposure of only 1 h was sufficient to initiate its stimulatory action on It and Iss. The stimulatory effect of insulin on these K+ currents was prevented by 2 microM cycloheximide, which in itself had no direct effect on these currents. 3. Disruption of the actin microfilament network with 1 microM cytochalasin D (CD) also prevented the stimulatory effect of 100 nM insulin on both It and Iss. Since CD was added 1 h after insulin, inhibitory effects on insulin signalling were ruled out. Adding CD (1 microM) 5-9 h after insulin, when currents were already augmented, had no effect (up to 50 min exposure). Incubating control cells for 6-10 h with 1 microM CD had no effect on any of the currents measured. 4. Stabilization of the actin network by pre-exposure to 2.5 microM phalloidin restored the stimulatory effect of insulin, in the continued presence of CD, ruling out any effects of CD on components other than the cytoskeleton. 5. The stimulatory effect of insulin was also prevented by incubating cells with insulin in the presence of the microtubule-disrupting agent colchicine (5 microM). 6. These results suggest that the insulin-mediated augmentation of K+ currents in diabetic myocytes requires protein synthesis, possibly of K+ channels, as well as an intact cytoskeleton. The possibility that newly formed channels translocate to the plasma membrane in a process dependent on different elements of the cytoskeleton is discussed.

Outward Bound Outcome Model Validation and Multilevel Modeling

ERIC Educational Resources Information Center

Luo, Yuan-Chun

2011-01-01

This study was intended to measure construct validity for the Outward Bound Outcomes Instrument (OBOI) and to predict outcome achievement from individual characteristics and course attributes using multilevel modeling. A sample of 2,340 participants was collected by Outward Bound USA between May and September 2009 using the OBOI. Two phases of…

Outward Bound Giwaykiwin: Connecting to Land and Culture through Indigenous Outdoor Education

ERIC Educational Resources Information Center

Lowan, Greg

2007-01-01

Outward Bound Canada's (OBC) Giwaykiwin Program was founded in 1985 in response to a recognized need for programming specific to students from Indigenous backgrounds. The Giwaykiwin program aims to integrate Outward Bound (OB) and Indigenous philosophies and traditions. Giwaykiwin means "coming home" in Ojibwa and signifies the program's…

Helical unwinding and side-chain unlocking unravel the outward open conformation of the melibiose transporter

NASA Astrophysics Data System (ADS)

Wang, Li-Ying; Ravi, Vidhya M.; Leblanc, Gérard; Padrós, Esteve; Cladera, Josep; Perálvarez-Marín, Alex

2016-09-01

Molecular dynamics simulations have been used to study the alternate access mechanism of the melibiose transporter from Escherichia coli. Starting from the outward-facing partially occluded form, 2 out of 12 simulations produced an outward full open form and one partially open, whereas the rest yielded fully or partially occluded forms. The shape of the outward-open form resembles other outward-open conformations of secondary transporters. During the transporter opening, conformational changes in some loops are followed by changes in the periplasm region of transmembrane helix 7. Helical curvature relaxation and unlocking of hydrophobic and ionic locks promote the outward opening of the transporter making accessible the substrate binding site. In particular, FRET studies on mutants of conserved aromatic residues of extracellular loop 4 showed lack of substrate binding, emphasizing the importance of this loop for making crucial interactions that control the opening of the periplasmic side. This study indicates that the alternate access mechanism for the melibiose transporter fits better into a flexible gating mechanism rather than the archetypical helical rigid-body rocker-switch mechanism.

David Triggle: Research collaborations and scientific exchanges with the China Pharmaceutical University, Nanjing, China.

PubMed

Dai, De-Zai

2015-11-15

Over the period 1995-2012, David Triggle was a frequent visitor to the China Pharmaceutical University in Nanjing, China making many important contributions that enhanced the activities of the Research Division of Pharmacology at the University. In addition to providing collegial advice and facilitating interactions with the international pharmacological community, Professor Triggle's international reputation as a thought leader in the field of ion channel research and drug discovery provided important insights into the potential pathophysiological and therapeutic effects of targeting ion channels. This included the L-type calcium channel and the outward delayed rectified potassium currents of rapid (IKr) and slow (IKs) components in the myocardium. The Nanjing research team had been particularly interested in ion channel dysfunction in the context of cardiac arrhythmias, remodeling and drug discovery. With Professor Triggle's assistance, the relationship between an increase in ICa.L and other biological events including an enhancement of IKr and IKr currents, NADPH oxidase and endothelin receptor activation, down regulation of calcium modulating protein FKBP12.6, sarco/endoplasmic reticulum Ca(2+)ATPse (SERCA2A) and calsequens 2 (CASQ2), calcium leak at the diastole and endoplasmic reticulum stress, were evaluated and are discussed. Additionally, the organization of several international symposia was greatly enhanced by input from Professor Triggle as were the published research manuscripts in international pharmacology journals. During his association with the China Pharmaceutical University, Professor Triggle aided in enhancing the scientific standing of the Pharmacology department and was a highly effective ambassador for international research cooperation. Copyright © 2015. Published by Elsevier Inc.

Representing delayed force feedback as a combination of current and delayed states.

PubMed

Avraham, Guy; Mawase, Firas; Karniel, Amir; Shmuelof, Lior; Donchin, Opher; Mussa-Ivaldi, Ferdinando A; Nisky, Ilana

2017-10-01

To adapt to deterministic force perturbations that depend on the current state of the hand, internal representations are formed to capture the relationships between forces experienced and motion. However, information from multiple modalities travels at different rates, resulting in intermodal delays that require compensation for these internal representations to develop. To understand how these delays are represented by the brain, we presented participants with delayed velocity-dependent force fields, i.e., forces that depend on hand velocity either 70 or 100 ms beforehand. We probed the internal representation of these delayed forces by examining the forces the participants applied to cope with the perturbations. The findings showed that for both delayed forces, the best model of internal representation consisted of a delayed velocity and current position and velocity. We show that participants relied initially on the current state, but with adaptation, the contribution of the delayed representation to adaptation increased. After adaptation, when the participants were asked to make movements with a higher velocity for which they had not previously experienced with the delayed force field, they applied forces that were consistent with current position and velocity as well as delayed velocity representations. This suggests that the sensorimotor system represents delayed force feedback using current and delayed state information and that it uses this representation when generalizing to faster movements. NEW & NOTEWORTHY The brain compensates for forces in the body and the environment to control movements, but it is unclear how it does so given the inherent delays in information transmission and processing. We examined how participants cope with delayed forces that depend on their arm velocity 70 or 100 ms beforehand. After adaptation, participants applied opposing forces that revealed a partially correct representation of the perturbation using the current and the delayed information. Copyright © 2017 the American Physiological Society.

Rectification of Acetylcholine-Elicited Currents in PC12 Pheochromocytoma Cells

NASA Astrophysics Data System (ADS)

Ifune, C. K.; Steinbach, J. H.

1990-06-01

The current-voltage (I-V) relationship for acetylcholine-elicited currents in the rat pheochromocytoma cell line PC12 is nonlinear. Two voltage-dependent processes that could account for the whole-cell current rectification were examined, receptor channel gating and single receptor channel permeation. We found that both factors are involved in the rectification of the whole-cell currents. The voltage dependence of channel gating determines the shape of the I-V curve at negative potentials. The single-channel I-V relationship is inwardly rectifying and largely responsible for the characteristic shape of the whole-cell I-V curve at positive potentials. The rectification of the single-channel currents is produced by the voltage-dependent block of outward currents by intracellular Mg2+ ions.

A Means-End Investigation of Outcomes Associated with Outward Bound and NOLS Programs

ERIC Educational Resources Information Center

Goldenberg, Marni; Pronsolino, Dan

2008-01-01

This study compares outcomes associated with participation in Outward Bound (OB) and National Outdoor Leadership Schools (NOLS) courses in the United States. OB and NOLS (two of the largest providers of outdoor adventure education [OAE] courses) combined saw more than 30,000 students in 2006 (NOLS, n.d.; Outward Bound, n.d.). Comparing these two…

Convergent regulation of the lysosomal two-pore channel-2 by Mg2+, NAADP, PI(3,5)P2 and multiple protein kinases

PubMed Central

Jha, Archana; Ahuja, Malini; Patel, Sandip; Brailoiu, Eugen; Muallem, Shmuel

2014-01-01

Lysosomal Ca2+ homeostasis is implicated in disease and controls many lysosomal functions. A key in understanding lysosomal Ca2+ signaling was the discovery of the two-pore channels (TPCs) and their potential activation by NAADP. Recent work concluded that the TPCs function as a PI(3,5)P2 activated channels regulated by mTORC1, but not by NAADP. Here, we identified Mg2+ and the MAPKs, JNK and P38 as novel regulators of TPC2. Cytoplasmic Mg2+ specifically inhibited TPC2 outward current, whereas lysosomal Mg2+ partially inhibited both outward and inward currents in a lysosomal lumen pH-dependent manner. Under controlled Mg2+, TPC2 is readily activated by NAADP with channel properties identical to those in response to PI(3,5)P2. Moreover, TPC2 is robustly regulated by P38 and JNK. Notably, NAADP-mediated Ca2+ release in intact cells is regulated by Mg2+, PI(3,5)P2, and P38/JNK kinases, thus paralleling regulation of TPC2 currents. Our data affirm a key role for TPC2 in NAADP-mediated Ca2+ signaling and link this pathway to Mg2+ homeostasis and MAP kinases, pointing to roles for lysosomal Ca2+ in cell growth, inflammation and cancer. PMID:24502975

Convergent regulation of the lysosomal two-pore channel-2 by Mg²⁺, NAADP, PI(3,5)P₂ and multiple protein kinases.

PubMed

Jha, Archana; Ahuja, Malini; Patel, Sandip; Brailoiu, Eugen; Muallem, Shmuel

2014-03-03

Lysosomal Ca(2+) homeostasis is implicated in disease and controls many lysosomal functions. A key in understanding lysosomal Ca(2+) signaling was the discovery of the two-pore channels (TPCs) and their potential activation by NAADP. Recent work concluded that the TPCs function as a PI(3,5)P2 activated channels regulated by mTORC1, but not by NAADP. Here, we identified Mg(2+) and the MAPKs, JNK and P38 as novel regulators of TPC2. Cytoplasmic Mg(2+) specifically inhibited TPC2 outward current, whereas lysosomal Mg(2+) partially inhibited both outward and inward currents in a lysosomal lumen pH-dependent manner. Under controlled Mg(2+), TPC2 is readily activated by NAADP with channel properties identical to those in response to PI(3,5)P2. Moreover, TPC2 is robustly regulated by P38 and JNK. Notably, NAADP-mediated Ca(2+) release in intact cells is regulated by Mg(2+), PI(3,5)P2, and P38/JNK kinases, thus paralleling regulation of TPC2 currents. Our data affirm a key role for TPC2 in NAADP-mediated Ca(2+) signaling and link this pathway to Mg(2+) homeostasis and MAP kinases, pointing to roles for lysosomal Ca(2+) in cell growth, inflammation and cancer.

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

The Cooperstown Outward Bound Summer Program: An Informal Look at the Program's Impact on the Lives of Students.

ERIC Educational Resources Information Center

Sakofs, Mitchell S.; And Others

During the summer of 1987, 29 students from the Cooperstown High School in New York received scholarships and participated in an Outward Bound course. This report presents the results of a study assessing the impact of the Outward Bound experience on these students. Data gathering instruments included: the Self Report Survey (SRS), developed by…

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.

Action potentials and ion conductances in wild-type and CALHM1-knockout type II taste cells

PubMed Central

Saung, Wint Thu; Foskett, J. Kevin

2017-01-01

Taste bud type II cells fire action potentials in response to tastants, triggering nonvesicular ATP release to gustatory neurons via voltage-gated CALHM1-associated ion channels. Whereas CALHM1 regulates mouse cortical neuron excitability, its roles in regulating type II cell excitability are unknown. In this study, we compared membrane conductances and action potentials in single identified TRPM5-GFP-expressing circumvallate papillae type II cells acutely isolated from wild-type (WT) and Calhm1 knockout (KO) mice. The activation kinetics of large voltage-gated outward currents were accelerated in cells from Calhm1 KO mice, and their associated nonselective tail currents, previously shown to be highly correlated with ATP release, were completely absent in Calhm1 KO cells, suggesting that CALHM1 contributes to all of these currents. Calhm1 deletion did not significantly alter resting membrane potential or input resistance, the amplitudes and kinetics of Na+ currents either estimated from action potentials or recorded from steady-state voltage pulses, or action potential threshold, overshoot peak, afterhyperpolarization, and firing frequency. However, Calhm1 deletion reduced the half-widths of action potentials and accelerated the deactivation kinetics of transient outward currents, suggesting that the CALHM1-associated conductance becomes activated during the repolarization phase of action potentials. NEW & NOTEWORTHY CALHM1 is an essential ion channel component of the ATP neurotransmitter release mechanism in type II taste bud cells. Its contribution to type II cell resting membrane properties and excitability is unknown. Nonselective voltage-gated currents, previously associated with ATP release, were absent in cells lacking CALHM1. Calhm1 deletion was without effects on resting membrane properties or voltage-gated Na+ and K+ channels but contributed modestly to the kinetics of action potentials. PMID:28202574

Action potentials and ion conductances in wild-type and CALHM1-knockout type II taste cells.

PubMed

Ma, Zhongming; Saung, Wint Thu; Foskett, J Kevin

2017-05-01

Taste bud type II cells fire action potentials in response to tastants, triggering nonvesicular ATP release to gustatory neurons via voltage-gated CALHM1-associated ion channels. Whereas CALHM1 regulates mouse cortical neuron excitability, its roles in regulating type II cell excitability are unknown. In this study, we compared membrane conductances and action potentials in single identified TRPM5-GFP-expressing circumvallate papillae type II cells acutely isolated from wild-type (WT) and Calhm1 knockout (KO) mice. The activation kinetics of large voltage-gated outward currents were accelerated in cells from Calhm1 KO mice, and their associated nonselective tail currents, previously shown to be highly correlated with ATP release, were completely absent in Calhm1 KO cells, suggesting that CALHM1 contributes to all of these currents. Calhm1 deletion did not significantly alter resting membrane potential or input resistance, the amplitudes and kinetics of Na + currents either estimated from action potentials or recorded from steady-state voltage pulses, or action potential threshold, overshoot peak, afterhyperpolarization, and firing frequency. However, Calhm1 deletion reduced the half-widths of action potentials and accelerated the deactivation kinetics of transient outward currents, suggesting that the CALHM1-associated conductance becomes activated during the repolarization phase of action potentials. NEW & NOTEWORTHY CALHM1 is an essential ion channel component of the ATP neurotransmitter release mechanism in type II taste bud cells. Its contribution to type II cell resting membrane properties and excitability is unknown. Nonselective voltage-gated currents, previously associated with ATP release, were absent in cells lacking CALHM1. Calhm1 deletion was without effects on resting membrane properties or voltage-gated Na + and K + channels but contributed modestly to the kinetics of action potentials. Copyright © 2017 the American Physiological Society.

Permeation and block of TRPV1 channels by the cationic lidocaine derivative QX-314

PubMed Central

Puopolo, Michelino; Binshtok, Alexander M.; Yao, Gui-Lan; Oh, Seog Bae; Woolf, Clifford J.

2013-01-01

QX-314 (N-ethyl-lidocaine) is a cationic lidocaine derivative that blocks voltage-dependent sodium channels when applied internally to axons or neuronal cell bodies. Coapplication of external QX-314 with the transient receptor potential vanilloid 1 protein (TRPV1) agonist capsaicin produces long-lasting sodium channel inhibition in TRPV1-expressing neurons, suggestive of QX-314 entry into the neurons. We asked whether QX-314 entry occurs directly through TRPV1 channels or through a different pathway (e.g., pannexin channels) activated downstream of TRPV1 and whether QX-314 entry requires the phenomenon of “pore dilation” previously reported for TRPV1. With external solutions containing 10 or 20 mM QX-314 as the only cation, inward currents were activated by stimulation of both heterologously expressed and native TRPV1 channels in rat dorsal root ganglion neurons. QX-314-mediated inward current did not require pore dilation, as it activated within several seconds and in parallel with Cs-mediated outward current, with a reversal potential consistent with PQX-314/PCs = 0.12. QX-314-mediated current was no different when TRPV1 channels were expressed in C6 glioma cells, which lack expression of pannexin channels. Rapid addition of QX-314 to physiological external solutions produced instant partial inhibition of inward currents carried by sodium ions, suggesting that QX-314 is a permeant blocker. Maintained coapplication of QX-314 with capsaicin produced slowly developing reduction of outward currents carried by internal Cs, consistent with intracellular accumulation of QX-314 to concentrations of 50–100 μM. We conclude that QX-314 is directly permeant in the “standard” pore formed by TRPV1 channels and does not require either pore dilation or activation of additional downstream channels for entry. PMID:23303863

The membrane current of single rod outer segments.

PubMed

Baylor, D A; Lamb, T D; Yau, K W

1979-03-01

1. Outer segments of individual rods in the retina of the toad, Bufo marinus, were drawn into a glass pipette to record the membrane current. 2. Light flashes evoked transient outward currents. The peak response amplitude was related to flash intensity by a Michaelis equation with half-saturating intensity about 1 photon mum-2. 3. The saturating response amplitude ranged up to 27 pA and corresponded closely to complete suppression of the steady inward current present in darkness. 4. For a given cell the saturating response amplitude varied linearly with the length of outer segment within the pipette. This is consistent with a uniform density of light-sensitive channels and negligible gradient of membrane potential along the outer segment. 5. Responses to bright flashes never showed the relaxation from an initial peak seen previously in intracellular voltage recordings, suggesting that the conductance change responsible for the relaxation does not occur in the outer segment. 6. Responses to local illumination of only the recorded outer segment were very similar to those obtained with diffuse light at the same intensity, indicating that peripheral rods made little contribution to the responses. 7. The spectral sensitivity of 'red' rods was consistent with a retinal1-based pigment with lambda max = 498 +/- 2 nm. 8. The kinetics of the response were consistent with four stages of delay affecting action of the internal transmitter. Responses were faster at the basal end of the outer segment than at the distal tip. 9. Background light reduced the sensitivity to a superposed dim test flash and shortened the time course of the response, indicating that adapting light modifies the kinetics and gain of the transduction mechanism within the outer segment. 10. Responses to dim lights exhibited pronounced fluctuations which are attributed in the succeeding paper (Baylor, Lamb & Yau, 1979) to the quantal nature of light.

Chloride currents activated by caffeine in rat intestinal smooth muscle cells.

PubMed Central

Ohta, T; Ito, S; Nakazato, Y

1993-01-01

1. Current responses to caffeine in single smooth muscle cells isolated from rat intestine were studied with the whole-cell patch clamp technique. Intracellular calcium concentration, [Ca2+]i, was simultaneously monitored with fura-2 (0.1 mM) introduced into the cell through a patch pipette. 2. With a potassium-containing pipette solution, caffeine (10 mM) produced an outward current at a holding potential of 0 mV and an inward current at -60 mV, both of which were accompanied by parallel increases in [Ca2+]i. The outward current response disappeared after the removal of K+ from pipette solutions, indicating that caffeine activates a Ca(2+)-activated K+ conductance. 3. When NaCl was present in both pipette and external solutions as the major constituent, caffeine evoked an inward current at -60 mV simultaneously with a rise in [Ca2+]i. The reversal potential (Er) of this current was about 0 mV. 4. Substitution of Tris+ or choline+ for external Na+ did not alter the Er. When external Cl- was replaced by thiocyanate-, iodide- or glutamate-, the Er changed to respectively -55, -38 and +35 mV. 5. The current response to caffeine decreased with increasing concentration of EGTA in the pipette solution. The caffeine-induced current and the intracellular Ca2+ transient was still observed for a few minutes after exposure of the cells to Ca(2+)-free external solution containing 2 mM EGTA. Caffeine failed to produce an inward current and Ca2+ transient after treatment with extracellular ryanodine. 6. It is concluded that caffeine caused an increase in membrane Cl- conductance and in K+ conductance resulting from a rise in [Ca2+]i derived from ryanodine-sensitive intracellular Ca2+ stores in isolated smooth muscle cells of the rat intestine. PMID:8229831

Observation and simulation of the ionosphere disturbance waves triggered by rocket exhausts

NASA Astrophysics Data System (ADS)

Lin, Charles C. H.; Chen, Chia-Hung; Matsumura, Mitsuru; Lin, Jia-Ting; Kakinami, Yoshihiro

2017-08-01

Observations and theoretical modeling of the ionospheric disturbance waves generated by rocket launches are investigated. During the rocket passage, time rate change of total electron content (rTEC) enhancement with the V-shape shock wave signature is commonly observed, followed by acoustic wave disturbances and region of negative rTEC centered along the trajectory. Ten to fifteen min after the rocket passage, delayed disturbance waves appeared and propagated along direction normal to the V-shape wavefronts. These observation features appeared most prominently in the 2016 North Korea rocket launch showing a very distinct V-shape rTEC enhancement over enormous areas along the southeast flight trajectory despite that it was also appeared in the 2009 North Korea rocket launch with the eastward flight trajectory. Numerical simulations using the physical-based nonlinear and nonhydrostatic coupled model of neutral atmosphere and ionosphere reproduce promised results in qualitative agreement with the characteristics of ionospheric disturbance waves observed in the 2009 event by considering the released energy of the rocket exhaust as the disturbance source. Simulations reproduce the shock wave signature of electron density enhancement, acoustic wave disturbances, the electron density depletion due to the rocket-induced pressure bulge, and the delayed disturbance waves. The pressure bulge results in outward neutral wind flows carrying neutrals and plasma away from it and leading to electron density depletions. Simulations further show, for the first time, that the delayed disturbance waves are produced by the surface reflection of the earlier arrival acoustic wave disturbances.

Active signal conduction through the sensory dendrite of a spider mechanoreceptor neuron.

PubMed

Gingl, Ewald; French, Andrew S

2003-07-09

Rapid responses to sensory stimulation are crucial for survival. This must be especially true for mechanical stimuli containing temporal information, such as vibration. Sensory transduction occurs at the tips of relatively long sensory dendrites in many mechanoreceptors of both vertebrates and invertebrates, but little is known about the electrical properties of these crucial links between transduction and action potential generation. The VS-3 slit-sense organ of the spider Cupiennius salei contains bipolar mechanosensory neurons that allow voltage-clamp recording from the somata, whereas mechanotransduction occurs at the tips of 100- to 200-microm-long sensory dendrites. We studied the properties of VS-3 sensory dendrites using three approaches. Voltage-jump experiments measured the spread of voltage outward from the soma by observing total mechanically transduced charge recovered at the soma as a function of time after a voltage jump. Frequency-response measurements between pseudorandom mechanical stimulation and somatic membrane potential estimated the passive cable properties of the dendrite for voltage spread in the opposite direction. Both of these sets of data indicated that the dendritic cable would significantly attenuate and retard a passively propagated receptor potential. Finally, current-clamp observations of receptor potentials and action potentials indicated that action potentials normally start at the distal dendrites and propagate regeneratively to the soma, reducing the temporal delay of passive conduction.

Mouths of the Amazon River, Brazil, South America

NASA Image and Video Library

1992-08-08

STS046-80-009 (31 July-8 Aug. 1992) --- A view of the mouth of the Amazon River and the Amazon Delta shows a large sediment plume expanding outward into the Atlantic Ocean. The sediment plume can be seen hugging the coast north of the Delta. This is caused by the west-northwest flowing Guyana Current. The large island of Marajo is partially visible through the clouds.

Plasma convection in Saturn's magnetosphere: A diagnosis using Cassini observations of the magnetic field spiral

NASA Astrophysics Data System (ADS)

Smith, Edward; Dougherty, Michele K.

The global distribution of plasma and its flows inside Saturn's magnetosphere is complex. The large satellites in the inner magnetosphere are a persistent source of plasma that must make its way into the outer magnetosphere and exit through the magnetotail. The mass loaded into the magnetic field stretches the field lines outward resulting in the formation of the equatorial current sheet. The outward radial flow causes the closed stretched fields to spiral out of magnetic meridian planes. The angle associated with the spiralling is given by the ratio of the azimuthal field component, B , to the radial component Br : tan = B / Br . The magnetic spiral is directly related to the corresponding components of plasma velocity, v and v r, provided the conductivity of the ionosphere, , is high enough to enforce co-rotation of the field lines. If, as has been inferred, the conductivity is low, the field and plasma do not co-rotate and the conductivity also enters the expression for . Conditions are more uncertain further out in the magnetosphere where convective motions associated with magnetic reconnection between planetary and interplanetary fields and the motion of the shocked solar wind become dominant. The prevailing model is a superposition of two modes of plasma circulation inside the magnetosphere and magnetotail, the Dungey and Vasyliunas cycles, that depend on radial distance and local time with an x-line in the midnight sector that separates the two cycles. The measured spiral angle will be affected by this complexity and holds the promise of distinguishing the relative influences of v ,v r and . The two field components that define the spiral angle are also involved in the transfer of angular momentum from the ionosphere to the magnetospheric plasma and the outward mass flux. The spiral should also contain evidence, especially at high latitudes, of the return of the current to the ionosphere from the current sheet. Our major objective, therefore, is to characterize as a function of radius, latitude and local time using the global coverage provided by Cassini and apply the findings to the topics listed above.

Role of 5-HTTLPR polymorphism in the development of the inward/outward personality organization: a genetic association study.

PubMed

Nardi, Bernardo; Marini, Alessandra; Turchi, Chiara; Arimatea, Emidio; Tagliabracci, Adriano; Bellantuono, Cesario

2013-01-01

Reciprocity with primary caregivers affects subjects' adaptive abilities toward the construction of the most useful personal meaning organization (PMO) with respect to their developmental environment. Within cognitive theory the post-rationalist approach has outlined two basic categories of identity construction and of regulation of cognitive and emotional processes: the Outward and the Inward PMO. The presence of different, consistent clinical patterns in Inward and Outward subjects is paralleled by differences in cerebral activation during emotional tasks on fMRI and by different expression of some polymorphisms in serotonin pathways. Since several lines of evidence support a role for the 5-HTTLPR polymorphism in mediating individual susceptibility to environmental emotional stimuli, this study was conducted to investigate its influence in the development of the Inward/Outward PMO. PMO was assessed and the 5-HTTLPR polymorphism investigated in 124 healthy subjects who were subdivided into an Inward (n = 52) and an Outward (n = 72) group. Case-control comparisons of short allele (S) frequencies showed significant differences between Inwards and Outwards (p = 0.036, χ2 test; p = 0.026, exact test). Genotype frequencies were not significantly different although values slightly exceeded p ≤ 0.05 (p = 0.056, χ2 test; p = 0.059, exact test). Analysis of the 5-HTTLPR genotypes according to the recessive inheritance model showed that the S/S genotype increased the likelihood of developing an Outward PMO (p = 0.0178, χ2 test; p = 0.0143, exact test; OR = 3.43, CI (95%) = 1.188-9.925). A logistic regression analysis confirmed the association between short allele and S/S genotypes with the Outward PMO also when gender and age were considered. However none of the differences remained significant after correction for multiple testing, even though using the recessive model they approach significance. Overall our data seem to suggest a putative genetic basis for interindividual differences in PMO development.

Role of 5-HTTLPR Polymorphism in the Development of the Inward/Outward Personality Organization: A Genetic Association Study

PubMed Central

Nardi, Bernardo; Marini, Alessandra; Turchi, Chiara; Arimatea, Emidio; Tagliabracci, Adriano; Bellantuono, Cesario

2013-01-01

Reciprocity with primary caregivers affects subjects' adaptive abilities toward the construction of the most useful personal meaning organization (PMO) with respect to their developmental environment. Within cognitive theory the post-rationalist approach has outlined two basic categories of identity construction and of regulation of cognitive and emotional processes: the Outward and the Inward PMO. The presence of different, consistent clinical patterns in Inward and Outward subjects is paralleled by differences in cerebral activation during emotional tasks on fMRI and by different expression of some polymorphisms in serotonin pathways. Since several lines of evidence support a role for the 5-HTTLPR polymorphism in mediating individual susceptibility to environmental emotional stimuli, this study was conducted to investigate its influence in the development of the Inward/Outward PMO. PMO was assessed and the 5-HTTLPR polymorphism investigated in 124 healthy subjects who were subdivided into an Inward (n = 52) and an Outward (n = 72) group. Case-control comparisons of short allele (S) frequencies showed significant differences between Inwards and Outwards (p = 0.036, χ2 test; p = 0.026, exact test). Genotype frequencies were not significantly different although values slightly exceeded p≤0.05 (p = 0.056, χ2 test; p = 0.059, exact test). Analysis of the 5-HTTLPR genotypes according to the recessive inheritance model showed that the S/S genotype increased the likelihood of developing an Outward PMO (p = 0.0178, χ2 test; p = 0.0143, exact test; OR = 3.43, CI (95%) = 1.188–9.925). A logistic regression analysis confirmed the association between short allele and S/S genotypes with the Outward PMO also when gender and age were considered. However none of the differences remained significant after correction for multiple testing, even though using the recessive model they approach significance. Overall our data seem to suggest a putative genetic basis for interindividual differences in PMO development. PMID:24358153

Fast Simulations of Gas Sloshing and Cold Front Formation

NASA Technical Reports Server (NTRS)

Roediger, E.; ZuHone, J. A.

2011-01-01

We present a simplified and fast method for simulating minor mergers between galaxy clusters. Instead of following the evolution of the dark matter halos directly by the N-body method, we employ a rigid potential approximation for both clusters. The simulations are run in the rest frame of the more massive cluster and account for the resulting inertial accelerations in an optimised way. We test the reliability of this method for studies of minor merger induced gas sloshing by performing a one-to-one comparison between our simulations and hydro+N-body ones. We find that the rigid potential approximation reproduces the sloshing-related features well except for two artefacts: the temperature just outside the cold fronts is slightly over-predicted, and the outward motion of the cold fronts is delayed by typically 200 Myr. We discuss reasons for both artefacts.

Fast Simulations of Gas Sloshing and Cold Front Formation

NASA Technical Reports Server (NTRS)

Roediger, E.; ZuHone, J. A.

2012-01-01

We present a simplified and fast method for simulating minor mergers between galaxy clusters. Instead of following the evolution of the dark matter halos directly by the N-body method, we employ a rigid potential approximation for both clusters. The simulations are run in the rest frame of the more massive cluster and account for the resulting inertial accelerations in an optimised way. We test the reliability of this method for studies of minor merger induced gas sloshing by performing a one-to-one comparison between our simulations and hydro+N-body ones. We find that the rigid potential approximation reproduces the sloshing-related features well except for two artifacts: the temperature just outside the cold fronts is slightly over-predicted, and the outward motion of the cold fronts is delayed by typically 200 Myr. We discuss reasons for both artifacts.

Deletion of the Slo3 gene abolishes alkalization-activated K+ current in mouse spermatozoa

PubMed Central

Zeng, Xu-Hui; Yang, Chengtao; Kim, Sung Tae; Lingle, Christopher J.; Xia, Xiao-Ming

2011-01-01

Mouse spermatozoa express a pH-dependent K+ current (KSper) thought to be composed of subunits encoded by the Slo3 gene. However, the equivalence of KSper and Slo3-dependent current remains uncertain, because heterologous expression of Slo3 results in currents that are less effectively activated by alkalization than are native KSper currents. Here, we show that genetic deletion of Slo3 abolishes all pH-dependent K+ current at physiological membrane potentials in corpus epididymal sperm. A residual pH-dependent outward current (IKres) is observed in Slo3−/− sperm at potentials of >0 mV. Differential inhibition of KSper/Slo3 and IKres by clofilium reveals that the amplitude of IKres is similar in both wild-type (wt) and Slo3−/− sperm. The properties of IKres suggest that it likely represents outward monovalent cation flux through CatSper channels. Thus, KSper/Slo3 may account for essentially all mouse sperm K+ current and is the sole pH-dependent K+ conductance in these sperm. With physiological ionic gradients, alkalization depolarizes Slo3−/− spermatozoa, presumably from CatSper activation, in contrast to Slo3/KSper-mediated hyperpolarization in wt sperm. Slo3−/− male mice are infertile, but Slo3−/− sperm exhibit some fertility within in vitro fertilization assays. Slo3−/− sperm exhibit a higher incidence of morphological abnormalities accentuated by hypotonic challenge and also exhibit deficits in motility in the absence of bicarbonate, revealing a role of KSper under unstimulated conditions. Together, these results show that KSper/Slo3 is the primary spermatozoan K+ current, that KSper may play a critical role in acquisition of normal morphology and sperm motility when faced with hyperosmotic challenges, and that Slo3 is critical for fertility. PMID:21427226

Effects of premature stimulation on HERG K+ channels

PubMed Central

Lu, Yu; Mahaut-Smith, Martyn P; Varghese, Anthony; Huang, Christopher L-H; Kemp, Paul R; Vandenberg, Jamie I

2001-01-01

The unusual kinetics of human ether-à-go-go-related gene (HERG) K+ channels are consistent with a role in the suppression of arrhythmias initiated by premature beats. Action potential clamp protocols were used to investigate the effect of premature stimulation on HERG K+ channels, transfected in Chinese hamster ovary cells, at 37 °C. HERG K+ channel currents peaked during the terminal repolarization phase of normally paced action potential waveforms. However, the magnitude of the current and the time point at which conductance was maximal depended on the type of action potential waveform used (epicardial, endocardial, Purkinje fibre or atrial). HERG K+ channel currents recorded during premature action potentials consisted of an early transient outward current followed by a sustained outward current. The magnitude of the transient current component showed a biphasic dependence on the coupling interval between the normally paced and premature action potentials and was maximal at a coupling interval equivalent to 90% repolarization (APD90) for ventricular action potentials. The largest transient current response occurred at shorter coupling intervals for Purkinje fibre (APD90– 20 ms) and atrial (APD90– 30 ms) action potentials. The magnitude of the sustained current response following premature stimulation was similar to that recorded during the first action potential for ventricular action potential waveforms. However, for Purkinje and atrial action potentials the sustained current response was significantly larger during the premature action potential than during the normally paced action potential. A Markov model that included three closed states, one open and one inactivated state with transitions permitted between the pre-open closed state and the inactivated state, successfully reproduced our results for the effects of premature stimuli, both during square pulse and action potential clamp waveforms. These properties of HERG K+ channels may help to suppress arrhythmias initiated by early afterdepolarizations and premature beats in the ventricles, Purkinje fibres or atria. PMID:11744759

Estrogen Contributes to Gender Differences in Mouse Ventricular Repolarization

PubMed Central

Saito, Tomoaki; Ciobotaru, Andrea; Bopassa, Jean Chrisostome; Toro, Ligia; Stefani, Enrico; Eghbali, Mansoureh

2010-01-01

Rationale Fast-transient outward K+ (Ito,f) and ultra-rapid delayed rectifier K+ currents (IKur or IK,slow) contribute to mouse cardiac repolarization. Gender studies on these currents have reported conflicting results. Objective One key missing piece information in these studies is the animals’ estral stage. We decided to revisit gender-related differences in K+ currents, taking into consideration the females’ estral stage. Methods and Results We hypothesized that changes in estrogen levels during the estral cycle could play a role in determining the densities of K+ currents underlying ventricular repolarization. Peak total K+ current (IK,total) densities (pA/pF, at +40 mV) were much higher in males (48.6±3.0) than in females at estrus (27.2±2.3) but not at diestrus-2 (39.1±3.4). Underlying this change, Ito,f and IK,slow were lower in females at estrus vs males and diestrus-2 (IK,slow: male 21.9±1.8, estrus 14.6±0.6, diestrus-2 20.3±1.4; Ito,f: male 26.8±1.9, estrus 14.9±1.6, diestrus-2 22.1±2.1). The lower IK,slow in estrus was only due to IK,slow1 reduction without changes of IK,slow2. Estrogen treatment of ovariectomized mice decreased IK,total (46.4±3.0 to 28.4±1.6), Ito,f (26.6±1.6 to 12.8±1.0) and IK,slow (22.2±1.6 to 17.2±1.4). Transcript levels of Kv4.3 and Kv1.5 (underlying Ito,f and IK,slow, respectively) were lower in estrus vs. diestrus-2 and male. In ovariectomized mice, estrogen treatment resulted in downregulation of Kv4.3 and Kv1.5, but not Kv4.2, KChIP2 and Kv2.1 transcripts. K+ current reduction in high estrogenic conditions were associated with prolongation of the action potential duration and corrected QT interval. Conclusion Downregulation of Kv4.3 and Kv1.5 transcripts by estrogen are one mechanism defining gender-related differences in mouse ventricular repolarization. PMID:19608983

Stimulation of the BKCa channel in cultured smooth muscle cells of human trachea by magnolol

PubMed Central

Wu, S; Chen, C; Li, H; Lo, Y; Chen, S; Chiang, H

2002-01-01

Background: Magnolol, a compound isolated from the cortex of Magnolia officinalis, has been found to possess anti-allergic and anti-asthmatic activity. Methods: The effect of magnolol on ionic currents was studied in cultured smooth muscle cells of human trachea with the aid of the patch clamp technique. Results: In whole cell current recordings magnolol reversibly increased the amplitude of K+ outward currents. The increase in outward current caused by magnolol was sensitive to inhibition by iberiotoxin (200 nM) or paxilline (1 µM) but not by glibenclamide (10 µM). In inside out patches, magnolol added to the bath did not modify single channel conductance but effectively enhanced the activity of large conductance Ca2+ activated K+ (BKCa) channels. Magnolol increased the probability of these channel openings in a concentration dependent manner with an EC50 value of 1.5 µM. The magnolol stimulated increase in the probability of channels opening was independent of internal Ca2+. The application of magnolol also shifted the activation curve of BKCa channels to less positive membrane potentials. The change in the kinetic behaviour of BKCa channels caused by magnolol in these cells is the result of an increase in dissociation and gating constants. Conclusions: These results provide evidence that, in addition to the presence of antioxidative activity, magnolol is potent in stimulating BKCa channel activity in tracheal smooth muscle cells. The direct stimulation of these BKCa channels by magnolol may contribute to the underlying mechanism by which it acts as an anti-asthmatic compound. PMID:11809993

The NO donor DETA-NONOate reversibly activates an inward current in neurones and is not mediated by the released nitric oxide

PubMed Central

Thompson, AJ; Mander, PK; Brown, GC

2009-01-01

Background and purpose: It has been previously shown that high levels of nitric oxide (NO), from NO donors, kill neurones, but the mechanisms are unclear. Experimental approach: The effects of NO donors on the electrical properties of rat cultured cerebellar granule cells (CGC neurones) were investigated using the whole-cell patch-clamp technique. Key results: The NO donor (Z)-1-[2-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA-NONOate or NOC-18) caused a rapid, persistent, but fully reversible inward current that was associated with an increase in baseline noise and was concentration dependent (100 µM–10 mM). The response to 3 mM DETA-NONOate was completely inhibited by 1 mM gadolinium, but not by NO scavengers (1 mM haemoglobin or 1 mM PTIO) or glutamate receptor antagonists (10 µM MK-801 or 60 µM CNQX). Application of decomposed 3 mM DETA-NONOate or 3 mM nitrite had no effect. In contrast, the NO donor S-nitrosoglutathione (GSNO) caused a rapid, persistent, but fully reversible outward current that was also concentration dependent (1–10 mM). The 3 mM GSNO response was unaltered by NO scavengers, glutamate antagonists or gadolinium, but was mimicked by decomposed 3 mM GSNO and 3 mM oxidized glutathione. Conclusions and implications: These results suggest that DETA-NONOate directly activates cation-selective channels, causing an inward current in CGCs. In contrast, GSNO causes an outward current in these cells. Some of the effects of these NO donors are independent of NO, and thus caution is required in interpreting results when using high concentrations of these compounds. PMID:19785659

The NO donor DETA-NONOate reversibly activates an inward current in neurones and is not mediated by the released nitric oxide.

PubMed

Thompson, A J; Mander, P K; Brown, G C

2009-11-01

It has been previously shown that high levels of nitric oxide (NO), from NO donors, kill neurones, but the mechanisms are unclear. The effects of NO donors on the electrical properties of rat cultured cerebellar granule cells (CGC neurones) were investigated using the whole-cell patch-clamp technique. The NO donor (Z)-1-[2-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA-NONOate or NOC-18) caused a rapid, persistent, but fully reversible inward current that was associated with an increase in baseline noise and was concentration dependent (100 microM-10 mM). The response to 3 mM DETA-NONOate was completely inhibited by 1 mM gadolinium, but not by NO scavengers (1 mM haemoglobin or 1 mM PTIO) or glutamate receptor antagonists (10 microM MK-801 or 60 microM CNQX). Application of decomposed 3 mM DETA-NONOate or 3 mM nitrite had no effect. In contrast, the NO donor S-nitrosoglutathione (GSNO) caused a rapid, persistent, but fully reversible outward current that was also concentration dependent (1-10 mM). The 3 mM GSNO response was unaltered by NO scavengers, glutamate antagonists or gadolinium, but was mimicked by decomposed 3 mM GSNO and 3 mM oxidized glutathione. These results suggest that DETA-NONOate directly activates cation-selective channels, causing an inward current in CGCs. In contrast, GSNO causes an outward current in these cells. Some of the effects of these NO donors are independent of NO, and thus caution is required in interpreting results when using high concentrations of these compounds.

Developing rods transplanted into the degenerating retina of Crx-knockout mice exhibit neural activity similar to native photoreceptors

PubMed Central

Homma, Kohei; Okamoto, Satoshi; Mandai, Michiko; Gotoh, Norimoto; Rajasimha, Harsha K.; Chang, Yi-Sheng; Chen, Shan; Li, Wei; Cogliati, Tiziana; Swaroop, Anand; Takahashi, Masayo

2013-01-01

Replacement of dysfunctional or dying photoreceptors offers a promising approach for retinal neurodegenerative diseases, including age-related macular degeneration and retinitis pigmentosa. Several studies have demonstrated the integration and differentiation of developing rod photoreceptors when transplanted in wild type or degenerating retina; however, the physiology and function of the donor cells are not adequately defined. Here, we describe the physiological properties of developing rod photoreceptors that are tagged with GFP driven by the promoter of rod differentiation factor, Nrl. GFP-tagged developing rods show Ca2+ responses and rectifier outward currents that are smaller than those observed in fully developed photoreceptors, suggesting their immature developmental state. These immature rods also exhibit hyperpolarization-activated current (Ih) induced by the activation of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. When transplanted into the subretinal space of wild type or retinal degeneration mice, GFP-tagged developing rods can integrate into the photoreceptor outer nuclear layer in wild-type mouse retina, and exhibit Ca2+ responses and membrane current comparable to native rod photoreceptors. A proportion of grafted rods develop rhodopsin-positive outer segment-like structures within two weeks after transplantation into the retina of Crx-knockout mice, and produce rectifier outward current and Ih upon membrane depolarization and hyperpolarization. GFP-positive rods derived from induced pluripotent stem (iPS) cells also display similar membrane current Ih as native developing rod photoreceptors, express rod-specific phototransduction genes, and HCN-1 channels. We conclude that Nrl-promoter driven GFP-tagged donor photoreceptors exhibit physiological characteristics of rods and that iPS cell-derived rods in vitro may provide a renewable source for cell replacement therapy. PMID:23495178

Atrial cellular electrophysiological changes in patients with ventricular dysfunction may predispose to AF

PubMed Central

Workman, Antony J; Pau, Davide; Redpath, Calum J; Marshall, Gillian E; Russell, Julie A; Norrie, John; Kane, Kathleen A; Rankin, Andrew C

2009-01-01

Background Left ventricular systolic dysfunction (LVSD) is a risk factor for atrial fibrillation (AF), but the atrial cellular electrophysiological mechanisms in humans are unclear. Objective To investigate whether LVSD in patients who are in sinus rhythm (SR) is associated with atrial cellular electrophysiological changes which could predispose to AF. Methods Right atrial myocytes were obtained from 214 consenting patients in SR who were undergoing cardiac surgery. Action potentials or ion currents were measured using the whole-cell-patch clamp technique. Results The presence of moderate or severe LVSD was associated with a shortened atrial cellular effective refractory period, ERP (209±8 ms; 52 cells, 18 patients vs 233±7 ms; 134 cells, 49 patients; P<0.05); confirmed by multiple linear regression analysis. The LV ejection fraction (LVEF) was markedly lower in patients with moderate or severe LVSD (36±4%, n=15) than in those without LVSD (62±2%, n=31; P<0.05). In cells from patients with LVEF≤45%, the ERP and action potential duration at 90% repolarisation were shorter than in those from patients with LVEF>45%, by 24 and 18%, respectively. The LVEF and ERP were positively correlated (r=0.65, P<0.05). The L-type calcium ion current, inward rectifier potassium ion current, and sustained outward ion current was unaffected by LVSD. The transient outward potassium ion current was decreased by 34%, with a positive shift in its activation voltage, and no change in its decay kinetics. Conclusion LVSD in patients in SR is independently associated with a shortening of the atrial cellular ERP, which may be expected to contribute to a predisposition to AF. PMID:19324301

Modulation of ventricular transient outward K+ current by acidosis and its effects on excitation-contraction coupling

PubMed Central

Saegusa, Noriko; Garg, Vivek

2013-01-01

The contribution of transient outward current (Ito) to changes in ventricular action potential (AP) repolarization induced by acidosis is unresolved, as is the indirect effect of these changes on calcium handling. To address this issue we measured intracellular pH (pHi), Ito, L-type calcium current (ICa,L), and calcium transients (CaTs) in rabbit ventricular myocytes. Intracellular acidosis [pHi 6.75 with extracellular pH (pHo) 7.4] reduced Ito by ∼50% in myocytes with both high (epicardial) and low (papillary muscle) Ito densities, with little effect on steady-state inactivation and activation. Of the two candidate α-subunits underlying Ito, human (h)Kv4.3 and hKv1.4, only hKv4.3 current was reduced by intracellular acidosis. Extracellular acidosis (pHo 6.5) shifted Ito inactivation toward less negative potentials but had negligible effect on peak current at +60 mV when initiated from −80 mV. The effects of low pHi-induced inhibition of Ito on AP repolarization were much greater in epicardial than papillary muscle myocytes and included slowing of phase 1, attenuation of the notch, and elevation of the plateau. Low pHi increased AP duration in both cell types, with the greatest lengthening occurring in epicardial myocytes. The changes in epicardial AP repolarization induced by intracellular acidosis reduced peak ICa,L, increased net calcium influx via ICa,L, and increased CaT amplitude. In summary, in contrast to low pHo, intracellular acidosis has a marked inhibitory effect on ventricular Ito, perhaps mediated by Kv4.3. By altering the trajectory of the AP repolarization, low pHi has a significant indirect effect on calcium handling, especially evident in epicardial cells. PMID:23585132

Enhanced functional expression of transient outward current in hypertrophied feline myocytes.

PubMed

Ten Eick, R E; Zhang, K; Harvey, R D; Bassett, A L

1993-08-01

Cardiac hypertrophy can decrease myocardial contractility and alter the electrophysiological activity of the heart. It is well documented that action potentials recorded from hypertrophied feline ventricular cells can exhibit depressed plateau voltages and prolonged durations. Similar findings have been made by others in rabbit, rat, guinea pig, and human heart. Whole-cell patch voltage-clamp studies designed to explain these changes in the action potential suggest that the only component of the membrane current recorded from feline right ventricular (RV) myocytes found to be substantially different from normal is the 4-amino-pyridine-sensitive transient outward current (I(to)). However, it was not clear if the change in I(to) could explain the changes in the action potential of hypertrophied cardiocytes, nor was it clear if these changes reflect an alteration in the electrophysiological character of the channels underlying I(to). A kinetic comparison of I(to) elicited by hypertrophied RV myocytes with that elicited by comparable normal RV myocytes previously revealed no differences, suggesting that the increased magnitude of the peak I(to) recorded from hypertrophied myocytes arises because the current density increases and not because of any alteration in the kinetic parameters governing the current. This finding suggests that in hypertrophy additional normal channels are expressed rather than a kinetically different channel subtype emerging. Investigations designed to determine if enhancement of I(to) could explain the hypertrophy-induced changes in plateau voltage and action potential duration suggest that a change in I(to) density can indeed explain the entire effect of hypertrophy on RV action potentials. If this notion is correct, the likelihood of "sudden death" in patients with myocardial hypertrophy might be decreased by a blocker selective for cardiac I(to).

The Effects of Nicotinic and Muscarinic Receptor Activation on Patch-Clamped Cells in the Optic Tectum of Rana Pipiens

PubMed Central

Yu, C.-J.; Debski, E. A.

2008-01-01

Both nicotinic and muscarinic cholinergic receptors are present in the optic tectum. To begin to understand how the activation of these receptors affects visual activity patterns, we have determined the types of physiological responses induced by their activation. Using tectal brain slices from the leopard frog, we found that application of nicotine (100 μM) evoked long-lasting responses in 60% of patch-clamped tectal cells. Thirty percent of these responses consisted of an increase in spontaneous postsynaptic currents (sPSCs) and had both a glutamatergic and GABAergic component as determined by the use of 6-cyano-7-nitroquinoxaline-2,3-dione (50 μM) and bicuculline (25 μM), respectively. Remaining response types consisted of an inward membrane current (16%) and an increase in sPSCs combined with an inward membrane current (14%). All responses could be elicited in the presence of tetrodotoxin (0.5 μM). Muscarinic receptor-mediated responses, induced by carbachol (100 μM) application after nicotinic receptor desensitization, produced responses in 70% of tectal cells. In contrast to responses elicited by nicotine, carbachol-induced responses could be evoked multiple times without significant decrement. Responses consisted of either an outward current (57%), a decrease in sPSCs (5%) or an increase in sPSCs, with (almost 6%) or without (almost 3%) an outward current. The response elicited by carbachol was not predicted by the response of the cell to nicotine. Our results suggest that nicotinic receptors are found predominantly at presynaptic locations in the optic tectum while muscarinic receptors are most often present at postsynaptic sites. We conclude that both of these receptor types could substantially modulate visual activity by changing either the input to tectal neurons or the level of their response to that input. PMID:12676145

The effects of nicotinic and muscarinic receptor activation on patch-clamped cells in the optic tectum of Rana pipiens.

PubMed

Yu, C-J; Debski, E A

2003-01-01

Both nicotinic and muscarinic cholinergic receptors are present in the optic tectum. To begin to understand how the activation of these receptors affects visual activity patterns, we have determined the types of physiological responses induced by their activation. Using tectal brain slices from the leopard frog, we found that application of nicotine (100 microM) evoked long-lasting responses in 60% of patch-clamped tectal cells. Thirty percent of these responses consisted of an increase in spontaneous postsynaptic currents (sPSCs) and had both a glutamatergic and GABAergic component as determined by the use of 6-cyano-7-nitroquinoxaline-2,3-dione (50 microM) and bicuculline (25 microM), respectively. Remaining response types consisted of an inward membrane current (16%) and an increase in sPSCs combined with an inward membrane current (14%). All responses could be elicited in the presence of tetrodotoxin (0.5 microM). Muscarinic receptor-mediated responses, induced by carbachol (100 microM) application after nicotinic receptor desensitization, produced responses in 70% of tectal cells. In contrast to responses elicited by nicotine, carbachol-induced responses could be evoked multiple times without significant decrement. Responses consisted of either an outward current (57%), a decrease in sPSCs (5%) or an increase in sPSCs, with (almost 6%) or without (almost 3%) an outward current. The response elicited by carbachol was not predicted by the response of the cell to nicotine. Our results suggest that nicotinic receptors are found predominantly at presynaptic locations in the optic tectum while muscarinic receptors are most often present at postsynaptic sites. We conclude that both of these receptor types could substantially modulate visual activity by changing either the input to tectal neurons or the level of their response to that input.

Combination induction plasma tube and current concentrator for introducing a sample into a plasma

DOEpatents

Hull, Donald E.; Bieniewski, Thomas M.

1988-01-01

An induction plasma tube in combination with a current concentrator. The rent concentrator has a substantially cylindrical body having an open end and a partially closed end which defines an aperture. A first slot extends the longitudinal length of the cylindrical body and a second slot extends radially outward from the aperture. Together the first and second slots form a single L-shaped slot. The current concentrator is disposed within a volume bounded by an induction coil substantially along the axis thereof, and when power is applied to the induction coil a concentrated current is induced within the current concentrator aperture. The concentrator is moveable relative to the coil along the longitudinal axis of the coil to control the amount of current which is concentrated at the aperture.

Blockade by N-3 polyunsaturated fatty acid of the Kv4.3 current stably expressed in Chinese hamster ovary cells

PubMed Central

Singleton, C B; Valenzuela, S M; Walker, B D; Tie, H; Wyse, K R; Bursill, J A; Qiu, M R; Breit, S N; Campbell, T J

1999-01-01

The Kv4.3 gene is believed to encode a large proportion of the transient outward current (Ito), responsible for the early phase of repolarization of the human cardiac action potential. There is evidence that this current is involved in the dispersion of refractoriness which develops during myocardial ischaemia and which predisposes to the development of potentially fatal ventricular tachyarrhythmias. Epidemiological, clinical, animal, and cellular studies indicate that these arrhythmias may be ameliorated in myocardial ischaemia by n-3 polyunsaturated fatty acids (n-3 PUFA) present in fish oils. We describe stable transfection of the Kv4.3 gene into a mammalian cell line (Chinese hamster ovary cells), and using patch clamp techniques have shown that the resulting current closely resembles human Ito. The current is rapidly activating and inactivating, with both processes being well fit by double exponential functions (time constants of 3.8±0.2 and 5.3±0.4 ms for activation and 20.0±1.2 and 96.6±6.7 ms for inactivation at +45 mV at 23°C). Activation and steady state inactivation both show voltage dependence (V1/2 of activation=−6.7±2.5 mV, V1/2 of steady state inactivation=−51.3±0.2 mV at 23°C). Current inactivation and recovery from inactivation are faster at physiologic temperature (37°C) compared to room temperature (23°C). The n-3 PUFA docosahexaenoic acid blocks the Kv4.3 current with an IC50 of 3.6 μmol L−1. Blockade of the transient outward current may be an important mechanism by which n-3 PUFA provide protection against the development of ventricular fibrillation during myocardial ischaemia. PMID:10433502

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

Nonlinear reconnecting edge localized modes in current-carrying plasmas

DOE PAGES

Ebrahimi, F.

2017-05-22

Nonlinear edge localized modes in a tokamak are examined using global three-dimensional resistive magnetohydrodynamics simulations. Coherent current-carrying filament (ribbon-like) structures wrapped around the torus are nonlinearly formed due to nonaxisymmetric reconnecting current sheet instabilities, the so-called peeling-like edge localized modes. These fast growing modes saturate by breaking axisymmetric current layers isolated near the plasma edge and go through repetitive relaxation cycles by expelling current radially outward and relaxing it back. The local bidirectional fluctuation-induced electromotive force (emf) from the edge localized modes, the dynamo action, relaxes the axisymmetric current density and forms current holes near the edge. Furthermore, the three-dimensionalmore » coherent current-carrying filament structures (sometimes referred to as 3-D plasmoids) observed here should also have strong implications for solar and astrophysical reconnection.« less

Ringing After a High-Energy Collision: Ambipolar Oscillations During Impact Plasma Expansion

NASA Technical Reports Server (NTRS)

Zimmerman, M. I.; Farrell, W. M.; Stubbs, T. J.

2012-01-01

High-velocity impacts on the Moon and other airless bodies deliver energy and material to the lunar surface and exosphere. The target and i mpactor material may become vaporized and ionized to form a collision al plasma that expands outward and eventually becomes collisionless. In the present work, kinetic simulations of the later collision less stage of impact plasma expansion are performed. Attention is paid to characterizing "ambipolar oscillations" in which thermodynamic distur bances propagate outward to generate "ringing" within the expanding e lectron cloud, which could radiate an electromagnetic signature of lo cal plasma conditions. The process is not unlike a beam-plasma intera ction, with the perturbing electron population in the present case ac ting as a highly thermal "beam" that resonates along the expanding de nsity gradient. Understanding the electromagnetic aspects of impact p lasma expansion could provide insight into the lasting effects of nat ural, impact-generated currents on airless surfaces and charging haza rds to human exploration infrastructure and instrumentation.

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.

Some aspects of the cosmogonic outward migration of Neptune. Co-planar migration

NASA Astrophysics Data System (ADS)

Neslušan, L.; Jakubík, M.

2013-10-01

Considering a simple model of the cosmogonic outward migration of Neptune, we investigate if the assumption of an extremely low orbital inclination of small bodies in a once-existing proto-planetary disk could influence the structure of reservoirs of the objects in the trans-Neptunian region. We found no significant influence. Our models predict only the existence of the mean-motion resonances (MMRs) with Neptune 2:3, 3:5, 1:2, and an anemic scattered disk (MMRs 3:4, 5:7, and 9:11 are also indicated). To explain the classical Edgeworth-Kuiper belt, relatively abundant 4:7 and 2:5 MMRs, and the more numerous scattered disk, we need to assume that, e.g., the outer boundary of the original proto-planetary disk considerably exceeded the distance of the current Neptune's orbit (Neptune probably ended its migration at the distance, where the disk's density started to be sub-critical), or that some Pluto-sized objects resided inside the MMRs and in the distant parts of the original proto-planetary disk.

Effect of Er,Cr:YSGG laser on human dentin fluid flow.

PubMed

Al-Omari, Wael M; Palamara, Joseph E

2013-11-01

The aim of the current investigation was to assess the rate and magnitude of dentin fluid flow of dentinal surfaces irradiated with Er,Cr:YSGG laser. Twenty extracted third molars were sectioned, mounted, and irradiated with Er,Cr:YSGG laser at 3.5 and 4.5 W power settings. Specimens were connected to an automated fluid flow measurement apparatus (Flodec). The rate, magnitude, and direction of dentin fluid flow were recorded at baseline and after irradiation. Nonparametric Wilcoxon signed ranks repeated measure t test revealed a statistically significant reduction in fluid flow for all the power settings. The 4.5-W power output reduced the flow significantly more than the 3.5 W. The samples showed a baseline outward flow followed by inward flow due to irradiation then followed by decreased outward flow. It was concluded that Er,Cr:YSGG laser irradiation at 3.5 and 4.5 W significantly reduced dentinal fluid flow rate. The reduction was directly proportional to power output.

Outward Migration of Giant Planets in Orbital Resonance

NASA Astrophysics Data System (ADS)

D'Angelo, G.; Marzari, F.

2013-05-01

A pair of giant planets interacting with a gaseous disk may be subject to convergent orbital migration and become locked into a mean motion resonance. If the orbits are close enough, the tidal gaps produced by the planets in the disk may overlap. This represents a necessary condition to activate the outward migration of the pair. However, a number of other conditions must also be realized in order for this mechanism to operate. We have studied how disk properties, such as turbulence viscosity, temperature, surface density gradient, mass, and age, may affect the outcome of the outward migration process. We have also investigated the implications on this mechanism of the planets' gas accretion. If the pair resembles Jupiter and Saturn, the 3:2 orbital resonance may drive them outward until they reach stalling radii for migration, which are within ~10 AU of the star for disks representative of the early proto-solar nebula. However, planet post-formation conditions in the disk indicate that such planets become typically locked in the 1:2 orbital resonance, which does not lead to outward migration. Planet growth via gas accretion tends to alter the planets' mass-ratio and/or the disk accretion rate toward the star, reducing or inhibiting outward migration. Support from NASA Outer Planets Research Program and NASA Origins of Solar Systems Program is gratefully acknowledged.

'Oxytocin' for the outwardly oriented: Evidence for interactive effects in placebo responding.

PubMed

Darragh, Margot; Booth, Roger J; Consedine, Nathan S

2016-04-01

In order to harness the placebo effect for clinical benefit, more research is needed to determine who might be responsive to a placebo treatment. Recently, a two-faceted Transactional Model of Placebo Responding (TMPR) was offered, which suggests different personality types might respond to different contextual cues. The current study directly tested this model by manipulating treatment descriptors to match the two purported facets of responsiveness. Physically healthy volunteers (N=77) experiencing life stress were randomised to either the: (1) wait-list control, (2) 'serotonin treatment' group; or (3) 'oxytocin treatment' group. Both treatment groups received an 'antistress' intranasal spray (placebo). The 'serotonin' and 'oxytocin' treatments were described to appeal to the two purported facets responsiveness set out in the TMPR, inward and outward orientation. The BIS/BAS scale was used as proxies for inward (BIS) and outward (BAS) orientation. It was hypothesised that high BAS types would be more responsive to the 'oxytocin' and high BIS types would be more responsive to the 'serotonin'. Findings provide partial support for hypotheses, with high but not low BAS types having a greater response to the 'oxytocin' placebo; but the pattern of responses from high BIS types were contrary to predictions. Findings indicate interactions between personality type and environmental cues may contribute to placebo responding, but more research is needed to investigate possible operationalisations of responsiveness and the contextual cues to which different types may respond. Copyright © 2016 Elsevier Inc. All rights reserved.

Synergistic Effect of Light and Fusicoccin on Stomatal Opening 1

PubMed Central

Assmann, Sarah M.; Schwartz, Amnon

1992-01-01

Upon incubation of epidermal peels of Commelina communis in 1 millimolar KCl, a synergistic effect of light and low fusicoccin (FC) concentrations on stomatal opening is observed. In 1 millimolar KCl, stomata remain closed even in the light. However, addition of 0.1 micromolar FC results in opening up to 12 micrometers. The same FC concentration stimulates less than 5 micrometers of opening in darkness. The synergistic effect (a) decreases with increasing FC or KCl concentrations; (b) is dark-reversible; (c) like stomatal opening in high KCl concentrations (120 millimolar) is partially inhibited by the K+ channel blocker, tetraethyl-ammonium+ (20 millimolar). In whole-cell patch-clamp experiments with guard cell protoplasts of Vicia faba, FC (1 or 10 micromolar) stimulates an increase in outward current that is essentially voltage independent between - 100 and +60 millivolts, and occurs even when the membrane potential is held at a voltage (−60 millivolts) at which K+ channels are inactivated. These results are indicative of FC activation of a H+ pump. FC effects on the magnitude of inward and outward K+ currents are not observed. Epidermal peel and patch clamp data are both consistent with the hypothesis that the plasma membrane H+ ATPase of guard cells is a primary locus for the FC effect on stomatal apertures. PMID:16668799

METHOD OF PRODUCING AND ACCELERATING AN ION BEAM

NASA Technical Reports Server (NTRS)

Foster, John E. (Inventor)

2005-01-01

A method of producing and accelerating an ion beam comprising the steps of providing a magnetic field with a cusp that opens in an outward direction along a centerline that passes through a vertex of the cusp: providing an ionizing gas that sprays outward through at least one capillary-like orifice in a plenum that is positioned such that the orifice is on the centerline in the cusp, outward of the vortex of the cusp; providing a cathode electron source, and positioning it outward of the orifice and off of the centerline; and positively charging the plenum relative to the cathode electron source such that the plenum functions as m anode. A hot filament may be used as the cathode electron source, and permanent magnets may be used to provide the magnetic field.

Current Vaccine Shortages and Delays

MedlinePlus

... value="Submit" /> Related Links Vaccines & Immunizations Current Vaccine Shortages & Delays Recommend on Facebook Tweet Share Compartir ... vaccination are included in this update. Chart of Vaccines* in Delay or Shortage National Vaccine Supply Shortages ...

Current limiting mechanisms in electron and ion beam experiments

NASA Technical Reports Server (NTRS)

Olsen, R. C.

1990-01-01

The emission and collection of current from satellites or rockets in the ionosphere is a process which, at equilibrium, requires a balance between inward and outward currents. In most active experiments in the ionosphere and magnetosphere, the emitted current exceeds the integrated thermal current by one or more orders of magnitude. The system response is typically for the emitted current to be limited by processes such as differential charging of insulating surfaces, interactions between an emitted beam and the local plasma, and interactions between the beam and local neutral gas. These current limiting mechanisms have been illustrated for 20 years in sounding rocket and satellite experiments, which are reviewed here. Detailed presentations of the Spacecraft Charging at High Altitude (SCATHA) electron and ion gun experiments are used to demonstrate the general range of observed phenomena.

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

Calcium-activated K(+) channel (K(Ca)3.1) activity during Ca(2+) store depletion and store-operated Ca(2+) entry in human macrophages.

PubMed

Gao, Ya-dong; Hanley, Peter J; Rinné, Susanne; Zuzarte, Marylou; Daut, Jurgen

2010-07-01

STIM1 'senses' decreases in endoplasmic reticular (ER) luminal Ca(2+) and induces store-operated Ca(2+) (SOC) entry through plasma membrane Orai channels. The Ca(2+)/calmodulin-activated K(+) channel K(Ca)3.1 (previously known as SK4) has been implicated as an 'amplifier' of the Ca(2+)-release activated Ca(2+) (CRAC) current, especially in T lymphocytes. We have previously shown that human macrophages express K(Ca)3.1, and here we used the whole-cell patch-clamp technique to investigate the activity of these channels during Ca(2+) store depletion and store-operated Ca(2+) influx. Using RT-PCR, we found that macrophages express the elementary CRAC channel components Orai1 and STIM1, as well as Orai2, Orai3 and STIM2, but not the putatively STIM1-activated channels TRPC1, TRPC3-7 or TRPV6. In whole-cell configuration, a robust Ca(2+)-induced outwardly rectifying K(+) current inhibited by clotrimazole and augmented by DC-EBIO could be detected, consistent with K(Ca)3.1 channel current (also known as intermediate-conductance IK1). Introduction of extracellular Ca(2+) following Ca(2+) store depletion via P2Y(2) receptors induced a robust charybdotoxin (CTX)- and 2-APB-sensitive outward K(+) current and hyperpolarization. We also found that SOC entry induced by thapsigargin treatment induced CTX-sensitive K(+) current in HEK293 cells transiently expressing K(Ca)3.1. Our data suggest that SOC and K(Ca)3.1 channels are tightly coupled, such that a small Ca(2+) influx current induces a much large K(Ca)3.1 channel current and hyperpolarization, providing the necessary electrochemical driving force for prolonged Ca(2+) signaling and store repletion. Copyright 2010 Elsevier Ltd. All rights reserved.

Substrate transport pathway inside outward open conformation of EmrD: a molecular dynamics simulation study.

PubMed

Xianwei, Tan; Diannan, Lu; Boxiong, Wang

2016-07-19

The EmrD transporter, which is a classical major facilitator superfamily (MFS) protein, can extrude a range of drug molecules out of E. coil. The drug molecules transport through the channel of MFS in an outward open state, an important issue in research about bacterial drug resistance, which however, is still unknown. In this paper, we construct a starting outward-open model of the EmrD transporter using a state transition method. The starting model is refined by a conventional molecular dynamics simulation. Locally enhanced sampling simulation (LES) is used to validate the outward-open model of EmrD. In the locally enhanced sampling simulation, ten substrates are placed along the channel of the outward-open EmrD, and these substrates are sampled in the outward-open center cavity. It is found that the translocation pathway of these substrates from the inside to the outside of the cell through the EmrD transporter is composed of two sub-pathways, one sub-pathway, including H2, H4, and H5, and another sub-pathway, including H8, H10, and H11. The results give us have a further insight to the ways of substrate translocation of an MFS protein. The model method is based on common features of an MFS protein, so this modeling method can be used to construct various MFS protein models which have a desired state with other conformations not known in the alternating-access mechanism.

Inhibitory effects of purified antibody against α-1 repeat (117-137) on Na(+)-Ca(2+) exchange and L-type Ca(2+) currents in rat cardiomyocytes.

PubMed

Feng, Qi-Long; Wu, Dong-Mei; Cui, Xiang-Li; Zhao, Hua-Chen; Lin, Yuan-Yuan; Zhao, Lu-Ying; Wu, Bo-Wei

2010-10-25

Considering that α-1 repeat region may be involved in the ion binding and translocation of Na(+)-Ca(2+) exchanger (NCX), it is possible that the antibodies against NCX α-1 repeat may have a crucial action on NCX activity. The aim of the present study is to investigate the effect of antibody against α-1 repeat (117-137), designated as α-1(117-137), on NCX activity. The antibody against the synthesized α-1(117-137) was prepared and affinity-purified. Whole-cell patch clamp technique was used to study the change of Na(+)-Ca(2+) exchange current (I(Na/Ca)) in adult rat cardiomyocytes. To evaluate the functional specificity of this antibody, its effects on L-type Ca(2+) current (I(Ca,L)), voltage-gated Na(+) current (I(Na)) and delayed rectifier K(+) current (I(K)) were also observed. The amino acid sequences of α-1(117-137) in NCX and residues 1 076-1 096 within L-type Ca(2+) channel were compared using EMBOSS Pairwise Alignment Algorithms. The results showed that outward and inward I(Na/Ca) were decreased by the antibody against α-1(117-137) dose-dependently in the concentration range from 10 to 160 nmol/L, with IC(50) values of 18.9 nmol/L and 22.4 nmol/L, respectively. Meanwhile, the antibody also decreased I(Ca,L) in a concentration-dependent manner with IC(50) of 22.7 nmol/L. No obvious effects of the antibody on I(Na) and I(K) were observed. Moreover, comparison of the amino acid sequences showed there was 23.8% sequence similarity between NCX α-1(117-137) and residues 1 076-1 096 within L-type Ca(2+) channel. These results suggest that antibody against α-1(117-137) is a blocking antibody to NCX and can also decrease I(Ca,L) in a concentration-dependent manner, while it does not have obvious effects on I(Na) and I(K).

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

Stoltzfus-Dueck, T.; Scott, B.

An often-neglected portion of the radialmore » $$\\boldsymbol{E}\\times \\boldsymbol{B}$$ drift is shown to drive an outward flux of co-current momentum when free energy is transferred from the electrostatic potential to ion parallel flows. This symmetry breaking is fully nonlinear, not quasilinear, necessitated simply by free-energy balance in parameter regimes for which significant energy is dissipated via ion parallel flows. The resulting rotation peaking is counter-current and has a scaling and order of magnitude that are comparable with experimental observations. Finally, the residual stress becomes inactive when frequencies are much higher than the ion transit frequency, which may explain the observed relation of density peaking and counter-current rotation peaking in the core.« less

Is slack an intrinsic seizure terminator?

PubMed

Igelström, Kajsa M

2013-06-01

Understanding how epileptic seizures are initiated and propagated across large brain networks is difficult, but an even greater mystery is what makes them stop. Failure of spontaneous seizure termination leads to status epilepticus-a state of uninterrupted seizure activity that can cause death or permanent brain damage. Global factors, like changes in neuromodulators and ion concentrations, are likely to play major roles in spontaneous seizure cessation, but individual neurons also have intrinsic active ion currents that may contribute. The recently discovered gene Slack encodes a sodium-activated potassium channel that mediates a major proportion of the outward current in many neurons. Although given little attention, the current flowing through this channel may have properties consistent with a role in seizure termination.

Long Duration Responses in Squid Giant Axons Injected with 134Cesium Sulfate Solutions

PubMed Central

Sjodin, R. A.

1966-01-01

Giant axons from the squid were injected with 1.5 M cesium sulfate solutions containing the radioactive isotopes 42K and 134Cs. These axons, when stimulated, gave characteristic long duration action potentials lasting between 5 and 45 msec. The effluxes of 42K and 134Cs were measured both under resting conditions and during periods of repetitive stimulation. During the lengthened responses there were considerable increases in potassium efflux but only small increases in cesium efflux. The selectivity of the delayed rectification process was about 9 times greater for potassium ions than for cesium ions. The data suggest that internal cesium ions inhibit the outward potassium movement occurring during an action potential. The extra potassium effluxes taking place during excitation appear to be reduced in the presence of cesium ions to values between 7 and 22% of those expected in the absence of cesium inhibition. PMID:11526828

Coupling of an acoustic wave to shear motion due to viscous heating

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

Liu, Bin; Goree, J.

2016-07-15

Viscous heating due to shear motion in a plasma can result in the excitation of a longitudinal acoustic wave, if the shear motion is modulated in time. The coupling mechanism is a thermal effect: time-dependent shear motion causes viscous heating, which leads to a rarefaction that can couple into a longitudinal wave, such as an acoustic wave. This coupling mechanism is demonstrated in an electrostatic three-dimensional (3D) simulation of a dusty plasma, in which a localized shear flow is initiated as a pulse, resulting in a delayed outward propagation of a longitudinal acoustic wave. This coupling effect can be profoundmore » in plasmas that exhibit localized viscous heating, such as the dusty plasma we simulated using parameters typical of the PK-4 experiment. We expect that a similar phenomenon can occur with other kinds of plasma waves.« less

DSS range delay calibrations: Current performance level

NASA Technical Reports Server (NTRS)

Spradlin, G. L.

1976-01-01

A means for evaluating Deep Space Station (DSS) range delay calibration performance was developed. Inconsistencies frequently noted in these data are resolved. Development of the DSS range delay data base is described. The data base is presented with comments regarding apparent discontinuities. Data regarding the exciter frequency dependence of the delay values are presented. The improvement observed in the consistency of current DSS range delay calibration data over the performance previously observed is noted.

Nicotine is a potent blocker of the cardiac A-type K(+) channels. Effects on cloned Kv4.3 channels and native transient outward current.

PubMed

Wang, H; Shi, H; Zhang, L; Pourrier, M; Yang, B; Nattel, S; Wang, Z

2000-09-05

Nicotine is a main constituent of cigarette smoke and smokeless tobacco, known to increase the risk of sudden cardiac death. This study aimed at establishing ionic mechanisms underlying potential electrophysiological effects of nicotine. Effects of nicotine on Kv4.3 and Kv4.2 channels expressed in Xenopus oocytes were studied at the whole-cell and single-channel levels. The effects of nicotine on the transient outward K(+) current (I:(to)) were studied by use of whole-cell patch-clamp techniques in canine ventricular myocytes. Nicotine potently inhibited Kv4 current. The concentration for half-maximal inhibition (IC(50)) was 40+/-4 nmol/L, and the current was abolished by 100 micromol/L nicotine. The IC(50) for block of native I:(to) was 270+/-43 nmol/L. The steady-state activation properties of Kv4.3 and I:(to) were unaltered by nicotine, whereas positive shifts of the inactivation curves were observed. Of the total inhibition of Kv4.3 and I:(to) by nicotine, 40% was due to tonic block and 60% was attributable to use-dependent block. Activation, inactivation, and reactivation kinetics were not significantly changed by nicotine. Nicotine reduced single-channel conductance, open probability, and open time but increased the closed time of Kv4.3. The effects of nicotine were not altered by antagonists to various neurotransmitter receptors, indicating direct effects on I:(to) channels. Nicotine is a potent inhibitor of cardiac A-type K(+) channels, with blockade probably due to block of closed and open channels. This action may contribute to the ability of nicotine to affect cardiac electrophysiology and induce arrhythmias.

A mathematical model of the electrophysiological alterations in rat ventricular myocytes in type-I diabetes.

PubMed

Pandit, Sandeep V; Giles, Wayne R; Demir, Semahat S

2003-02-01

Our mathematical model of the rat ventricular myocyte (Pandit et al., 2001) was utilized to explore the ionic mechanism(s) that underlie the altered electrophysiological characteristics associated with the short-term model of streptozotocin-induced, type-I diabetes. The simulations show that the observed reductions in the Ca(2+)-independent transient outward K(+) current (I(t)) and the steady-state outward K(+) current (I(ss)), along with slowed inactivation of the L-type Ca(2+) current (I(CaL)), can result in the prolongation of the action potential duration, a well-known experimental finding. In addition, the model demonstrates that the slowed reactivation kinetics of I(t) in diabetic myocytes can account for the more pronounced rate-dependent action potential duration prolongation in diabetes, and that a decrease in the electrogenic Na(+)-K(+) pump current (I(NaK)) results in a small depolarization in the resting membrane potential (V(rest)). This depolarization reduces the availability of the Na(+) channels (I(Na)), thereby resulting in a slower upstroke (dV/dt(max)) of the diabetic action potential. Additional simulations suggest that a reduction in the magnitude of I(CaL), in combination with impaired sarcoplasmic reticulum uptake can lead to a decreased sarcoplasmic reticulum Ca(2+) load. These factors contribute to characteristic abnormal [Ca(2+)](i) homeostasis (reduced peak systolic value and rate of decay) in myocytes from diabetic animals. In combination, these simulation results provide novel information and integrative insights concerning plausible ionic mechanisms for the observed changes in cardiac repolarization and excitation-contraction coupling in rat ventricular myocytes in the setting of streptozotocin-induced, type-I diabetes.

Outward Bound Goes to the Inner City.

ERIC Educational Resources Information Center

Buchanan, David

1993-01-01

A program at the Thompson Island Outward Bound Education Center in Boston (Massachusetts) supplements the traditional program of ropes and rocks with community service, giving urban students opportunities to try out new leadership skills in local neighborhoods. (MLF)

Fading Away

NASA Image and Video Library

2009-06-09

This NAC image from MESSENGER’s second Mercury flyby shows a crater with a set of light-colored rays radiating outward from it. Such rays are formed when an impact excavates material from below the surface and throws it outward from the crater.

Demonstration of current drive by a rotating magnetic dipole field

NASA Astrophysics Data System (ADS)

Giersch, L.; Slough, J. T.; Winglee, R.

2007-04-01

Abstract.A dipole-like rotating magnetic field was produced by a pair of circular, orthogonal coils inside a metal vacuum chamber. When these coils were immersed in plasma, large currents were driven outside the coils: the currents in the plasma were generated and sustained by the rotating magnetic dipole (RMD) field. The peak RMD-driven current was at roughly two RMD coil radii, and this current (60 kA m-) was sufficient to reverse the ambient magnetic field (33 G). Plasma density, electron temperature, magnetic field and current probes indicated that plasma formed inside the coils, then expanded outward until the plasma reached equilibrium. This equilibrium configuration was adequately described by single-fluid magnetohydrodynamic equilibrium, wherein the cross product of the driven current and magnetic filed was approximately equal to the pressure gradient. The ratio of plasma pressure to magnetic field pressure, β, was locally greater than unity.

Apparatus and Method for Compensating for Process, Voltage, and Temperature Variation of the Time Delay of a Digital Delay Line

NASA Technical Reports Server (NTRS)

Seefeldt, James (Inventor); Feng, Xiaoxin (Inventor); Roper, Weston (Inventor)

2013-01-01

A process, voltage, and temperature (PVT) compensation circuit and a method of continuously generating a delay measure are provided. The compensation circuit includes two delay lines, each delay line providing a delay output. The two delay lines may each include a number of delay elements, which in turn may include one or more current-starved inverters. The number of delay lines may differ between the two delay lines. The delay outputs are provided to a combining circuit that determines an offset pulse based on the two delay outputs and then averages the voltage of the offset pulse to determine a delay measure. The delay measure may be one or more currents or voltages indicating an amount of PVT compensation to apply to input or output signals of an application circuit, such as a memory-bus driver, dynamic random access memory (DRAM), a synchronous DRAM, a processor or other clocked circuit.

[The modification of electrophysiology affected by ectopic synapse in ON-retinal bipolar cells of RCS rats].

PubMed

Zhang, Chen-xing; Yin, Zheng-qin; Weng, Chuan-huang; Zeng, Yu-xiao

2011-03-01

To study the influence of the ectopic synapse for electrophysiological characteristics modification in ON retinal bipolar cells (ON-RBCs) of RCS rat. Immunofluorescence of the retinal frozen section was taken in P60 d, P90 d of RCS rat (RCS) and control rat (CTR) with the anti-mGluR6 and anti-Synaptophysin, Lucifer Yellow staining solo ON-RBCs was taken in all the group. The whole cell recording was performed in the retinal slice of P60 d, P90 d in RCS and CTR. The modification of the passive membrane properties and the outward currents properties in RCS-ON-RBCs, CTR-ON-RBCs and CTR-OFF-RBCs were observed. RCS-ON-RBCs stretched out the ectopic neurite in different direction and the activity of synapse could be detected around the ectopic neurite. From Pn60d, passive membrane properties of RCS-ON-RBCs kept immature, The RMP in RCS-ON-RBCs and CTR-ON-RBCs were (-61.8 ± 3.07), (-50.44 ± 1.36) mV and (-63.1 ± 2.59), (-48.37 ± 3.69) mV when P60 d and P90 d, there ware significantly higher than CTR group (t = 2.191, 2.435, 5.817, 6.912;P < 0.05). The IR in RCS-ON-RBCs and CTR-ON-RBCs were (323.3 ± 42.6), (337.6 ± 71.3) MΩ and (321.2 ± 58.6), (340.3 ± 62.8) MΩ when P60 d and P90 d, there ware significantly higher than CTR group (t = 3.561, 1.987, 5.211, 4.034; P < 0.05). Outward currents were recorded when giving hyper- and depolarized voltage steps. In retinal degeneration, the amplitude of outward currents in RCS-ON-RBCs is significantly different with CTR-ON-RBCs (t = 5.561, 6.341; P < 0.05) or CTR-OFF-RBCs (t = 5.357, 6.997; P < 0.05). The ectopic neurite from RCS-ON-RBCs has the possibility for translating the signal. In retinitis pigmentosa, the modification of electrophysiology characteristics in RCS-ON-RBCs was significantly different with CTR-ON-RBCs and CTR-OFF-RBCs. Influence with the ectopic neurite is the possible cause.

A slow calcium-dependent component of charge movement in Rana temporaria cut twitch fibres.

PubMed

Hui, C S

1998-06-15

1. Charge movement was studied in highly stretched frog cut twitch fibres in a double Vaseline-gap voltage-clamp chamber, with the internal solution containing either 0.1 mM EGTA or 20 mM EGTA plus 1. 8 mM total Ca2+. 2. Fibres were stimulated with TEST pulses lasting 100-400 ms. Replacement of the external Cl- with an 'impermeant' anion, such as SO42-, CH3SO3-, gluconate or glutamate, greatly reduced the calcium-dependent Cl- current in the ON segment and generated a slowly decaying inward OFF current in charge movement traces. 3. Application of 20 mM EGTA to the internal solution abolished the slow inward OFF current, implying that the activation of the current depended on the presence of Ca2+ in the myoplasm. The possibility that the slow inward OFF current was carried by cations flowing inwards or anions flowing outwards was studied and determined to be unlikely. 4. During a long (2000 ms) TEST pulse, a slowly decaying ON current was also observed. When the slow ON and OFF currents were included as parts of the total charge movement, ON-OFF charge equality was preserved. This slow capacitive current is named Idelta. 5. When Cl- was the major anion in the external solution, the OFF Idelta was mostly cancelled by a slow outward current carried by the inflow of Cl-. 6. The OFF Idelta component showed a rising phase. The average values of the rising time constants in CH3SO3- and SO42- were similar and about half of that in gluconate. 7. The OFF Idelta component in CH3SO3- had a larger magnitude and longer time course than that in SO42-. The maximum amount of Qdelta in CH3SO3- was about three times as much as that in SO42-, whereas the voltage dependence of Qdelta was similar in the two solutions. 8. Since the existence of Qdelta depends on the presence of Ca2+ in the myoplasm, it is speculated that Qdelta could be a function of intracellular calcium release.

Delayed Intermodal Contingency Affects Young Children's Recognition of Their Current Self

ERIC Educational Resources Information Center

Miyazaki, Michiko; Hiraki, Kazuo

2006-01-01

This study investigated whether 2-, 3-, and 4-year-olds use their video feedback as a reflection of their current state, even when their feedback was presented with a short temporal delay. In Experiment 1, the effects of 1- and 2-s delayed feedback were examined on an analog of the mark test. In the case of live and 1-s delayed feedback,…

Development of a current sheet in the wake of a fast coronal mass ejection

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

Ling, A. G.; Webb, D. F.; Burkepile, J. T.

2014-04-01

A bright ray that developed in the wake of a fast coronal mass ejection (CME) on 2005 September 7 presents a unique opportunity to study the early development and physical characteristics of a reconnecting current sheet (CS). Polarization brightness images from the Mk4 K-Coronameter at the Mauna Loa Solar Observatory are used to determine the structure of the ray along its axis low in the corona as it progressed outward. Coverage of the early development of the ray out to ∼1.3 R {sub ☉} for a period of ∼27 hr after the start of the event enables for the firstmore » time in white light a measurement of a CME CS from the top of the arcade to the base of the flux rope. Measured widths of the ray are combined to obtain the kinematics of the upper and lower {sup Y-}points described in reconnection flux-rope models such as that of Lin and Forbes. The time dependence of these points are used to derive values for the speed and acceleration of the growth of the CS. We note the appearance of a large structure which increases in size as it expands outward in the early development of the ray and an apparent oscillation with a period of ∼0.5 hr in the position angle of the ray.« less

Mefenamic acid bi-directionally modulates the transient outward K{sup +} current in rat cerebellar granule cells

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

Zhang Man; Shi Wenjie; Fei Xiaowei

2008-02-01

The effect of non-steroidal anti-inflammatory drugs (NSAIDs) on ion channels has been widely studied in several cell models, but less is known about their modulatory mechanisms. In this report, the effect of mefenamic acid on voltage-activated transient outward K{sup +} current (I{sub A}) in cultured rat cerebellar granule cells was investigated. At a concentration of 5 {mu}M to 100 {mu}M, mefenamic acid reversibly inhibited I{sub A} in a dose-dependent manner. However, mefenamic acid at a concentration of 1 {mu}M significantly increased the amplitude of I{sub A} to 113 {+-} 1.5% of the control. At more than 10 {mu}M, mefenamic acidmore » inhibited the amplitude of I{sub A} without any effect on activation or inactivation. In addition, a higher concentration of mefenamic acid induced a significant acceleration of recovery from inactivation with an increase of the peak amplitude elicited by the second test pulse. Intracellular application of mefenamic acid could significantly increase the amplitude of I{sub A}, but had no effect on the inhibition induced by extracellular mefenamic acid, implying that mefenamic acid may exert its effect from both inside and outside the ion channel. Furthermore, the activation of current induced by intracellular application of mefenamic acid was mimicked by other cyclooxygenase inhibitors and arachidonic acid. Our data demonstrate that mefenamic acid is able to bi-directionally modulate I{sub A} channels in neurons at different concentrations and by different methods of application, and two different mechanisms may be involved.« less

The Cosmic Battery in Astrophysical Accretion Disks

NASA Astrophysics Data System (ADS)

Contopoulos, Ioannis; Nathanail, Antonios; Katsanikas, Matthaios

2015-06-01

The aberrated radiation pressure at the inner edge of the accretion disk around an astrophysical black hole imparts a relative azimuthal velocity on the electrons with respect to the ions which gives rise to a ring electric current that generates large-scale poloidal magnetic field loops. This is the Cosmic Battery established by Contopoulos and Kazanas in 1998. In the present work we perform realistic numerical simulations of this important astrophysical mechanism in advection-dominated accretion flows, ADAFs. We confirm the original prediction that the inner parts of the loops are continuously advected toward the central black hole and contribute to the growth of the large-scale magnetic field, whereas the outer parts of the loops are continuously diffusing outward through the turbulent accretion flow. This process of inward advection of the axial field and outward diffusion of the return field proceeds all the way to equipartition, thus generating astrophysically significant magnetic fields on astrophysically relevant timescales. We confirm that there exists a critical value of the magnetic Prandtl number between unity and 10 in the outer disk above which the Cosmic Battery mechanism is suppressed.

Implementation of a transcutaneous charger for fully implantable middle ear hearing device.

PubMed

Lim, H; Yoon, Y; Lee, C; Park, I; Song, B; Cho, J

2005-01-01

A transcutaneous charger for the fully implantable middle ear hearing device (F-IMEHD), which can monitor the charging level of battery, has been designed and implemented. In order to recharge the battery of F-IMEHD, the electromagnetic coupling between primary coil at outer body and secondary coil at inner body has been used. Considering the implant condition of the F-IMEHD, the primary coil and the secondary coil have been designed. Using the resonance of LC tank circuit at each coil, transmission efficiency was increased. Since the primary and the secondary coil are magnetically coupled, the current variation of the primary coil is related with the impedance of internal resonant circuit. Using the principle mentioned above, the implanted module could transmit outward the information about charging state of battery or coupling between two coils by the changing internal impedance. As in the demonstrated results of experiment, the implemented charger has supplied the sufficient operating voltage for the implanted battery within about 10 mm distance. And also, it has been confirmed that the implanted module can transmit information outward by control of internal impedance.

Momentum flux parasitic to free-energy transfer

DOE PAGES

Stoltzfus-Dueck, T.; Scott, B.

2017-05-11

An often-neglected portion of the radialmore » $$\\boldsymbol{E}\\times \\boldsymbol{B}$$ drift is shown to drive an outward flux of co-current momentum when free energy is transferred from the electrostatic potential to ion parallel flows. This symmetry breaking is fully nonlinear, not quasilinear, necessitated simply by free-energy balance in parameter regimes for which significant energy is dissipated via ion parallel flows. The resulting rotation peaking is counter-current and has a scaling and order of magnitude that are comparable with experimental observations. Finally, the residual stress becomes inactive when frequencies are much higher than the ion transit frequency, which may explain the observed relation of density peaking and counter-current rotation peaking in the core.« less

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

The turbulent generation of outward traveling Alfvenic fluctuations in the solar wind

NASA Technical Reports Server (NTRS)

Matthaeus, W. H.; Goldstein, M. L.; Montgomery, D. C.

1983-01-01

From an analysis of the incompressible MHD equations, it is concluded that the frequent observation of outward propagating Alfvenic fluctuations in the solar wind can arise from early stages of in situ turbulent evolution, and need not reflect coronal processes.

Revealing an outward-facing open conformational state in a CLC Cl –/H + exchange transporter

DOE PAGES

Khantwal, Chandra M.; Abraham, Sherwin J.; Han, Wei; ...

2016-01-22

CLC secondary active transporters exchange Cl - for H + . Crystal structures have suggested that the conformational change from occluded to outward-facing states is unusually simple, involving only the rotation of a conserved glutamate (Glu ex ) upon its protonation. Using 19 F NMR, we show that as [H + ] is increased to protonate Glu ex and enrich the outward-facing state, a residue ~20 Å away from Glu ex , near the subunit interface, moves from buried to solvent-exposed. Consistent with functional relevance of this motion, constriction via inter-subunit cross-linking reduces transport. Molecular dynamics simulations indicate that themore » cross-link dampens extracellular gate-opening motions. In support of this model, mutations that decrease steric contact between Helix N (part of the extracellular gate) and Helix P (at the subunit interface) remove the inhibitory effect of the cross-link. Together, these results demonstrate the formation of a previously uncharacterized 'outward-facing open' state, and highlight the relevance of global structural changes in CLC function.« less

Inhibitory action of ICI-182,780, an estrogen receptor antagonist, on BK(Ca) channel activity in cultured endothelial cells of human coronary artery.

PubMed

Liu, Yen-Chin; Lo, Yi-Ching; Huang, Chin-Wei; Wu, Sheng-Nan

2003-11-15

ICI-182,780 is known to be a selective inhibitor of the intracellular estrogen receptors. The effect of ICI-182,780 on ion currents was studied in cultured endothelial cells of human coronary artery. In whole-cell current recordings, ICI-182,780 reversibly decreased the amplitude of K(+) outward currents. The decrease in outward current caused by ICI-182,780 could be counteracted by further application of magnolol or nordihydroguaiaretic acid, yet not by 17beta-estradiol. Under current-clamp condition, ICI-182,780 (3microM) depolarized the membrane potentials of the cells, and magnolol (10 microM) or nordihydroguaiaretic acid (10 microM) reversed ICI-182,780-induced depolarization. In inside-out patches, ICI-182,780 added to the bath did not alter single-channel conductance of large-conductance Ca(2+)-activated K(+) channels (BK(Ca) channels), but decreased their open probability. ICI-182,780 reduced channel activity in a concentration-dependent manner with an IC(50) value of 3 microM. After BK(Ca) channel activity was suppressed by 2-methoxyestradiol (3 microM), subsequent application of ICI-182,780 (3 microM) did not further reduce the channel activity. The application of ICI-182,780 shifted the activation curve of BK(Ca) channels to positive potentials. Its decrease in the open probability primarily involved a reduction in channel open duration. ICI-182,780 also suppressed the proliferation of these endothelial cells with an IC(50) value of 2 microM. However, in coronary smooth muscle cells, a bell-shaped concentration-response curve for the ICI-182,780 effect on BK(Ca) channel activity was observed. This study provides evidence that ICI-182,780 can inhibit BK(Ca) channels in vascular endothelial cells in a mechanism unlikely to be linked to its anti-estrogen activity. The inhibitory effects on these channels may partly contribute to the underlying mechanisms by which ICI-182,780 affects endothelial function.

Modulation of contraction by intracellular Na+ via Na(+)-Ca2+ exchange in single shark (Squalus acanthias) ventricular myocytes.

PubMed Central

Näbauer, M; Morad, M

1992-01-01

1. The effect of direct alteration of intracellular Na+ concentration on contractile properties of whole-cell clamped shark ventricular myocytes was studied using an array of 256 photodiodes to monitor the length of the isolated myocytes. 2. In myocytes dialysed with Na(+)-free solution, the voltage dependence of Ca2+ current (ICa) and contraction were similar and bell shaped. Contractions activated at all voltages were completely suppressed by nifedipine (5 microM), and failed to show significant tonic components, suggesting dependence of the contraction on Ca2+ influx through the L-type Ca2+ channel. 3. In myocytes dialysed with 60 mM Na+, a ICa-dependent and a ICa-independent component of contraction could be identified. The Ca2+ current-dependent component was prominent in voltages between -30 to +10 mV. The ICa-independent contractions were maintained for the duration of depolarization, increased with increasing depolarization between +10 to +100 mV, and were insensitive to nifedipine. 4. In such myocytes, repolarization produced slowly decaying inward tail currents closely related to the time course of relaxation and the degree of shortening prior to repolarization. 5. With 60 mM Na+ in the pipette solution, positive clamp potentials activated decaying outward currents which correlated to the size of contraction. These outward currents appeared to be generated by the Na(+)-Ca(2+)-exchanger since they depended on the presence of intracellular Na+, and were neither suppressed by nifedipine nor by K+ channel blockers. 6. The results suggest that in shark (Squalus acanthias) ventricular myocytes, which lack functionally relevant Ca2+ release pools, both Ca2+ channel and the Na(+)-Ca2+ exchanger deliver sufficient Ca2+ to activate contraction, though the effectiveness of the latter mechanism was highly dependent on the [Na+]i. PMID:1338467

Mouths of the Amazon River, Brazil, South America

NASA Technical Reports Server (NTRS)

1992-01-01

In this view of the Amazon River Mouth (0.0, 51.0W), a large sediment plume can be seen expanding outward into the Atlantic Ocean. The sediment plume can be seen hugging the coast north of the delta as a result of the northwest flowing coastal Guyana Current. In recent years, the flow of the Amazon has become heavily laden with sediment as soil runoff from the denuded landscape of the interior enters the Amazon River (and other rivers) drainage system.

Outward transport of high-temperature materials around the midplane of the solar nebula.

PubMed

Ciesla, Fred J

2007-10-26

The Stardust samples collected from Comet 81P/Wild 2 indicate that large-scale mixing occurred in the solar nebula, carrying materials from the hot inner regions to cooler environments far from the Sun. Similar transport has been inferred from telescopic observations of protoplanetary disks around young stars. Models for protoplanetary disks, however, have difficulty explaining the observed levels of transport. Here I report the results of a new two-dimensional model that shows that outward transport of high-temperature materials in protoplanetary disks is a natural outcome of disk formation and evolution. This outward transport occurs around the midplane of the disk.

Turbine assembly containing an inner shroud

DOEpatents

Bagepalli, Bharat Sampathkumaran; Corman, Gregory Scot; Dean, Anthony John; DiMascio, Paul Stephen; Mirdamadi, Massoud

2000-01-01

A turbine assembly having a turbine stator, a ceramic inner shroud, and a first spring. The stator has a longitudinal axis and an outer shroud block with opposing and longitudinally outward facing first and second sides. The first side has a longitudinally outward projecting first ledge and has a first side portion located radially outward of the first ledge. The ceramic inner shroud has a first hook portion longitudinally and radially surrounding the first ledge. The first spring is attached to one of the first side portion and the first hook portion and unattachedly and resiliently contacts the other of the first side portion and the first hook portion.

The Articulatory In-Out Effect Resists Oral Motor Interference

ERIC Educational Resources Information Center

Lindau, Berit; Topolinski, Sascha

2018-01-01

People prefer words with inward directed consonantal patterns (e.g., MENIKA) compared to outward patterns (KENIMA), because inward (outward) articulation movements resemble positive (negative) mouth actions such as swallowing (spitting). This effect might rely on covert articulation simulations, or subvocalizations, since it occurs also under…

Summer in the City

ERIC Educational Resources Information Center

Gewertz, Catherine

2005-01-01

This article describes the different experiences of the participants in an Outward Bound-sponsored "urban expedition" to New York City that was designed to make them better teachers by examining their beliefs and biases. The participants in this "urban expedition" came from schools that work with Outward Bound USA, the…

Colorado Outward Bound School Rafting Manual.

ERIC Educational Resources Information Center

Brown, Al

River rafting trips at the Colorado Outward Bound School (COBS) present participants with an opportunity for developing self-confidence, self-awareness, and concern for others through challenging and adventuresome group effort, combined with a program of instruction in rafting skills, safety consciousness, and awareness of the natural environment.…

Logistics Handbook, 1976. Colorado Outward Bound School.

ERIC Educational Resources Information Center

Colorado Outward Bound School, Denver.

Logistics, a support mission, is vital to the successful operation of the Colorado Outward Bound School (COBS) courses. Logistics is responsible for purchasing, maintaining, transporting, and replenishing a wide variety of items, i.e., food, mountaineering and camping equipment, medical and other supplies, and vehicles. The Logistics coordinator…

Does Anger Regulation Mediate the Discrimination-Mental Health Link among Mexican-Origin Adolescents? A Longitudinal Mediation Analysis Using Multilevel Modeling

PubMed Central

Park, Irene J. K.; Wang, Lijuan; Williams, David R.; Alegría, Margarita

2016-01-01

Although prior research has consistently documented the association between racial/ethnic discrimination and poor mental health outcomes, the mechanisms that underlie this link are still unclear. The present three-wave longitudinal study tested the mediating role of anger regulation in the discrimination—mental health link among 269 Mexican-origin adolescents (Mage = 14.1 years, SD = 1.6; 57% girls), 12 – 17 years old. Three competing anger regulation variables were tested as potential mediators: outward anger expression, anger suppression, and anger control. Longitudinal mediation analyses were conducted using multilevel modeling that disaggregated within-person effects from between-person effects. Results indicated that outward anger expression was a significant mediator; anger suppression and anger control were not significant mediators. Within a given individual, greater racial/ethnic discrimination was associated with more frequent outward anger expression. In turn, more frequent outward anger expression was associated with higher levels of anxiety and depression at a given time point. Gender, age, and nativity status were not significant moderators of the hypothesized mediation models. By identifying outward anger expression as an explanatory mechanism in the discrimination-distress link among Latino youths, this study points to a malleable target for prevention and intervention efforts aimed at mitigating the detrimental impact of racism on Latino youths’ mental health during the developmentally critical period of adolescence. PMID:27893238

Active ion transport in dog tongue: a possible role in taste.

PubMed

DeSimone, J A; Heck, G L; DeSimone, S K

1981-11-27

An in vitro preparation of the dorsal epithelium of the dog tongue actively transports ions, producing a transepithelial potential difference characteristic of the ions and their concentration. Hypertonic sodium chloride solutions generally cause increased potentials and short-circuit currents and reduced resistances when placed on the mucosal surface. This hypertonic flux is eliminated by ouabain and is not found in ventral lingual epithelia. When either sodium acetate or tetramethylammonium chloride is substituted for sodium chloride in the mucosal medium, the currents are diminished but their sum at a given concentration approximates that for sodium chloride at the same concentration. This result suggests a current composed of inward sodium ion movement and outward chloride ion movement. Actively regulated potentials and currents, whether generated in the taste buds or in supporting cells, may be important in both normal chemotransduction and in taste responses evoked by currents passing through the tongue.

Transverse field focused system

DOEpatents

Anderson, O.A.

1983-06-01

It is an object of the invention to provide a transport apparatus for a high current negative-ion beam which will bend the beam around corners through a baffled path in a differential pump or a neutron trap. It is another object of the invention to provide a transport apparatus for a high current negative-ion beam which will allow gas molecules in the beam to exit outwardly from the transport apparatus. A further object of the invention is to provide a multi-stage accelerator for a high current negative-ion beam which will enable acceleration of the beam to very high energy levels with a minimum loss of current carrying capacity. A still further object of the invention is to provide an apparatus for transport or accelertion of a sheet beam of negative ions which is shaped to confine the beam against divergence or expansion.

Urocortin2 prolongs action potential duration and modulates potassium currents in guinea pig myocytes and HEK293 cells.

PubMed

Yang, Li-Zhen; Zhu, Yi-Chun

2015-07-05

We previously reported that activation of corticotropin releasing factor receptor type 2 by urocortin2 up-regulates both L-type Ca(2+) channels and intracellular Ca(2+) concentration in ventricular myocytes and plays an important role in cardiac contractility and arrhythmogenesis. This study goal was to further test the hypothesis that urocortin2 may modulate action potentials as well as rapidly and slowly activating delayed rectifier potassium currents. With whole cell patch-clamp techniques, action potentials and slowly activating delayed rectifier potassium currents were recorded in isolated guinea pig ventricular myocytes, respectively. And rapidly activating delayed rectifier potassium currents were tested in hERG-HEK293 cells. Urocortin2 produced a time- and concentration-dependent prolongation of action potential duration. The EC50 values of action potential duration and action potential duration at 90% of repolarization were 14.73 and 24.3nM respectively. The prolongation of action potential duration of urocortin2 was almost completely or partly abolished by H-89 (protein kinase A inhibitor) or KB-R7943 (Na(+)/Ca(2+) exchange inhibitor) pretreatment respectively. And urocortin2 caused reduction of rapidly activating delayed rectifier potassium currents in hERG-HEK293 cells. In addition, urocortin2 slowed the rate of slowly activating delayed rectifier potassium channel activation, and rightward shifted the threshold of slowly activating delayed rectifier potassium currents to more positive potentials. Urocortin2 prolonged action potential duration via activation of protein kinase A and Na(+)/ Ca(2+) exchange in isolated guinea pig ventricular myocytes in a time- and concentration- dependent manner. In hERG-HEK293 cells, urocortin2 reduced rapidly activating delayed rectifier potassium current density which may contribute to action potential duration prolongation. Copyright © 2015 Elsevier B.V. All rights reserved.

The role of Na-Ca exchange current in the cardiac action potential.

PubMed

Janvier, N C; Boyett, M R

1996-07-01

Since 1981, when Mullins published his provocative book proposing that the Na-Ca exchanger is electrogenic, it has been shown, first by computer simulation by Noble and later by experiment by various investigators, that inward iNaCa triggered by the Ca2+ transient is responsible for the low plateau of the atrial action potential and contributes to the high plateau of the ventricular action potential. Reduction or complete block of inward iNaCa by buffering intracellular Ca2+ with EGTA or BAPTA, by blocking SR Ca2+ release or by substituting extracellular Na+ with Li+ can result in a shortening of the action potential. The effect of block of outward iNaCa or complete block of both inward and outward iNaCa on the action potential has not been investigated experimentally, because of the lack of a suitable blocker, and remains a goal for the future. An increase in the intracellular Na+ concentration (after the application of cardiac glycoside or an increase in heart rate) or an increase in extracellular Ca2+ are believed to lead to an outward shift in iNaCa at plateau potentials and a shortening of the action potential. Changes in the Ca2+ transient are expected to result in changes in inward iNaCa and thus the action potential. This may explain the shortening of the premature action potential as well as the prolongation of the action potential when a muscle is allowed to shorten during the action potential. Inward iNaCa may play an important role in both normal and abnormal pacemaker activity in the heart.

Outward foreign direct investments and home country's economic growth

NASA Astrophysics Data System (ADS)

Ciesielska, Dorota; Kołtuniak, Marcin

2017-09-01

The study examines the time stability of the causality direction and cross-correlations between the home country's economic growth and pace of growth of its outward foreign direct investment (OFDI) stocks within the complex system of the Polish national economy. The research has been performed in order to verify, using both the time and frequency domains time series analyses, if economic agents' long term decisions on outward foreign direct investments, leading to cross-border value chains and production fragmentation processes, are of adaptive or predictive character. Consequently, the aim was to check if the home country's economic growth leads the internationalization processes of domestic enterprises, which stays in line with Dunning's Investment Development Path (IDP) paradigm, or if these complex processes, thanks to entrepreneurs' ability to formulate relevant rational expectations, precede the home country's economic growth, which would be supported with the introduction of the policy on reinforcing the internationalization processes of domestic enterprises. The presence of the unidirectional economic growth-led internationalization, consistent with the IDP concept's base assumptions, has been ascertained by the results of the short term Granger causality tests. Nevertheless, the results of the wavelet analyses, supported with the results of the econometric block exogeneity long term causality Wald tests, have revealed that in the long term the OFDI stocks' growth permanently precedes the home country's economic growth, which stays in the unequivocal contrast with the IDP paradigm's premises, as well as with the indicated above short term Granger causality tests' outcomes and indicates that economic agents' choices are not strictly of adaptive but also of predictive character, which influences the current state of knowledge on economic complex systems' characteristics. Such a result is of a great importance in the light of the existence of the significant and still unexploited internationalization potential of Polish enterprises.

A Route to Chaos after Bifurcation in a Two-section Semiconductor Laser Using Opto-electronic Delayed Feedback at Each In-current

NASA Astrophysics Data System (ADS)

Yan, Sen-lin

2014-12-01

We study dynamics in an opto-electronic delayed feedback two-section semiconductor laser. We predict theoretically that the system can result in bistability and bifurcation. We analyze numerically the route to chaos from stability to bifurcation by varying the delayed time, feedback strength and two in-currents. The system displays the four distinct types or modes of stable, periodic pulsed or self-pulsing, undamped oscillating or beating, and chaos. The frequency and intensity varying with the delayed time in the self-pulsation regions are discussed detailedly to find that the pulsing frequency is reduced with the long delayed time while the pulsing intensity is added. And the chaotic pulsing frequency is increased with the large in-current Ja. The laser relaxation oscillation frequency is decreased with the large in-current Jb. One in-current characterize dynamics in the laser to conduce to stable, periodic pulsed, beating and chaotic states by altering its values. The other in-current characterize dynamics in the chaotic laser to be controlled to a stable state after a road to quasi-period by adding the values.

Outdoor Education Academic Programs in the United States

ERIC Educational Resources Information Center

Bell, Brent J.; Seaman, Jayson; Trauntvein, Nate

2017-01-01

The growth of outdoor adventure programs developed, in part, from the Outward Bound movement in the 1970s (MacArthur, 1979; Outward Bound, 1968), which created a demand for specialized collegiate training. Since the inaugural conference on outdoor pursuits in higher education at Appalachian State University in 1974 (Smathers, 1974), approximately…

Outward Bound...Into the Mainstream of Education.

ERIC Educational Resources Information Center

Outward Bound, Inc., Andover, MA.

Outward Bound schools have instituted advanced courses designed specifically for adults engaged in education and youth work. Benefits for teachers include greater development of capacitites and potentialities, greater confidence in their abilities, and the ability to relate more effectively to others. Some of the specific training elements in an…

Instructor's Field Manual: North Carolina Outward Bound School.

ERIC Educational Resources Information Center

Outward Bound, Morganton, NC.

A supplement to the North Carolina Outward Bound School's Instructor's Handbook, this field manual presents useful, but not required, information gleaned from old timers and resource books which may enable the instructor to conduct a better course. Section one considers advantages and disadvantages and provides directions and topographical maps…

An Investigation of the Outward Bound Final Expedition

ERIC Educational Resources Information Center

Bobilya, Andrew J.; Kalisch, Ken; Daniel, Brad

2011-01-01

Research of wilderness programs indicates a clear need for additional investigation of specific program components and their influence on participant outcomes. This study examines one component of the Outward Bound wilderness program--the Final Expedition. The Final Expedition is a student-led wilderness expedition and is also referred to as an…

Adapted Outward Bound Programmes: An Alternative for Corrections.

ERIC Educational Resources Information Center

Cardwell, G. R.

A number of programmes for delinquent youth have been established throughout North America based on the Outward Bound concept: to involve volunteer participants in an outdoor programme which offers challenging and adventuresome tasks in a high-impact environment. Project D.A.R.E. (Development through Adventure, Responsibility and Education) in…

Alternate Semester 1972. An Evaluation.

ERIC Educational Resources Information Center

Copp, Barry D.; And Others

Five students from a Boston high school and 35 from Lincoln-Sudbury took part in an alternate semester consisting of 5 units: Outward Bound, environmental issues, urban, rural, and river/building. Students had to be juniors or seniors, have parental permission, and meet graduation requirements. The alternate semester began with Outward Bound, a…

Girls Leading Outward

ERIC Educational Resources Information Center

Hamed, Heather; Reyes, Jazmin; Moceri, Dominic C.; Morana, Laura; Elias, Maurice J.

2011-01-01

The authors describe a program implemented in Red Bank Middle School in New Jersey to help at-risk, minority middle school girls realize their leadership potential. The GLO (Girls Leading Outward) program was developed by the Developing Safe and Civil Schools Project at Rutgers University and is facilitated by university students. Selected middle…

Break-before-make CMOS inverter for power-efficient delay implementation.

PubMed

Puhan, Janez; Raič, Dušan; Tuma, Tadej; Bűrmen, Árpád

2014-01-01

A modified static CMOS inverter with two inputs and two outputs is proposed to reduce short-circuit current in order to increment delay and reduce power overhead where slow operation is required. The circuit is based on bidirectional delay element connected in series with the PMOS and NMOS switching transistors. It provides differences in the dynamic response so that the direct-path current in the next stage is reduced. The switching transistors are never ON at the same time. Characteristics of various delay element implementations are presented and verified by circuit simulations. Global optimization procedure is used to obtain the most power-efficient transistor sizing. The performance of the modified CMOS inverter chain is compared to standard implementation for various delays. The energy (charge) per delay is reduced up to 40%. The use of the proposed delay element is demonstrated by implementing a low-power delay line and a leading-edge detector cell.

Break-before-Make CMOS Inverter for Power-Efficient Delay Implementation

PubMed Central

Raič, Dušan

2014-01-01

A modified static CMOS inverter with two inputs and two outputs is proposed to reduce short-circuit current in order to increment delay and reduce power overhead where slow operation is required. The circuit is based on bidirectional delay element connected in series with the PMOS and NMOS switching transistors. It provides differences in the dynamic response so that the direct-path current in the next stage is reduced. The switching transistors are never ON at the same time. Characteristics of various delay element implementations are presented and verified by circuit simulations. Global optimization procedure is used to obtain the most power-efficient transistor sizing. The performance of the modified CMOS inverter chain is compared to standard implementation for various delays. The energy (charge) per delay is reduced up to 40%. The use of the proposed delay element is demonstrated by implementing a low-power delay line and a leading-edge detector cell. PMID:25538951

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.

Differences in transient outward currents of feline endocardial and epicardial myocytes.

PubMed

Furukawa, T; Myerburg, R J; Furukawa, N; Bassett, A L; Kimura, S

1990-11-01

Whole-cell voltage-clamp experiments were performed on enzymatically dissociated single ventricular myocytes harvested from feline endocardial and epicardial surfaces. The studies were designed to test the hypothesis that the differences in the amplitude of transient outward current (Ito) contribute to the difference in action potential configuration between endocardial and epicardial myocytes. In the control state, action potentials recorded from epicardial cells demonstrated a prominent notch between phases 1 and 2, and membrane current recordings displayed a prominent Ito, whereas in endocardial cells the notch in action potentials and Ito were small. External application of 4-aminopyridine (2 mM) reduced the amplitudes of notch and Ito in epicardial cells but not in endocardial cells. After application of 4-aminopyridine (2 mM) and caffeine (5 mM), the notch and Ito were abolished completely in both endocardial and epicardial cells. The first component of Ito (Ito1) was present in all epicardial cells studied (n = 20); it was absent in 12 of the 20 endocardial cells, and a small Ito1 was present in the remaining eight endocardial cells. The mean amplitude of Ito1 was significantly greater in epicardial than in endocardial cells. At a test voltage of +80 mV, the amplitude of Ito1 was 102.0 +/- 47.7 pA/pF in epicardial cells and 3.3 +/- 3.3 pA/pF in endocardial cells (p less than 0.01). The second component of Ito (Ito2) was present in all endocardial (n = 30) and epicardial (n = 30) cells studied. The amplitude of Ito2 was significantly greater in epicardial than in endocardial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Cooling arrangement for a superconducting coil

DOEpatents

Herd, K.G.; Laskaris, E.T.

1998-06-30

A superconducting device is disclosed, such as a superconducting rotor for a generator or motor. A vacuum enclosure has an interior wall surrounding a cavity containing a vacuum. A superconductive coil is placed in the cavity. A generally-annularly-arranged, thermally-conductive sheet has an inward-facing surface contacting generally the entire outward-facing surface of the superconductive coil. A generally-annularly-arranged coolant tube contains a cryogenic fluid and contacts a generally-circumferential portion of the outward-facing surface of the sheet. A generally-annularly-arranged, thermally-insulative coil overwrap generally circumferentially surrounds the sheet. The coolant tube and the inward-facing surface of the coil overwrap together contact generally the entire outward-facing surface of the sheet. 3 figs.

Selective control of cortical axonal spikes by a slowly inactivating K+ current

PubMed Central

Shu, Yousheng; Yu, Yuguo; Yang, Jing; McCormick, David A.

2007-01-01

Neurons are flexible electrophysiological entities in which the distribution and properties of ionic channels control their behaviors. Through simultaneous somatic and axonal whole-cell recording of layer 5 pyramidal cells, we demonstrate a remarkable differential expression of slowly inactivating K+ currents. Depolarizing the axon, but not the soma, rapidly activated a low-threshold, slowly inactivating, outward current that was potently blocked by low doses of 4-aminopyridine, α-dendrotoxin, and rTityustoxin-Kα. Block of this slowly inactivating current caused a large increase in spike duration in the axon but only a small increase in the soma and could result in distal axons generating repetitive discharge in response to local current injection. Importantly, this current was also responsible for slow changes in the axonal spike duration that are observed after somatic membrane potential change. These data indicate that low-threshold, slowly inactivating K+ currents, containing Kv1.2 α subunits, play a key role in the flexible properties of intracortical axons and may contribute significantly to intracortical processing. PMID:17581873

Signaling of Pigment-Dispersing Factor (PDF) in the Madeira Cockroach Rhyparobia maderae

PubMed Central

Funk, Nico W.; Giese, Maria; Baz, El-Sayed; Stengl, Monika

2014-01-01

The insect neuropeptide pigment-dispersing factor (PDF) is a functional ortholog of vasoactive intestinal polypeptide, the coupling factor of the mammalian circadian pacemaker. Despite of PDF's importance for synchronized circadian locomotor activity rhythms its signaling is not well understood. We studied PDF signaling in primary cell cultures of the accessory medulla, the circadian pacemaker of the Madeira cockroach. In Ca2+ imaging studies four types of PDF-responses were distinguished. In regularly bursting type 1 pacemakers PDF application resulted in dose-dependent long-lasting increases in Ca2+ baseline concentration and frequency of oscillating Ca2+ transients. Adenylyl cyclase antagonists prevented PDF-responses in type 1 cells, indicating that PDF signaled via elevation of intracellular cAMP levels. In contrast, in type 2 pacemakers PDF transiently raised intracellular Ca2+ levels even after blocking adenylyl cyclase activity. In patch clamp experiments the previously characterized types 1–4 could not be identified. Instead, PDF-responses were categorized according to ion channels affected. Application of PDF inhibited outward potassium or inward sodium currents, sometimes in the same neuron. In a comparison of Ca2+ imaging and patch clamp experiments we hypothesized that in type 1 cells PDF-dependent rises in cAMP concentrations block primarily outward K+ currents. Possibly, this PDF-dependent depolarization underlies PDF-dependent phase advances of pacemakers. Finally, we propose that PDF-dependent concomitant modulation of K+ and Na+ channels in coupled pacemakers causes ultradian membrane potential oscillations as prerequisite to efficient synchronization via resonance. PMID:25269074

Enhancement of delayed-rectifier potassium conductance by low concentrations of local anaesthetics in spinal sensory neurones

PubMed Central

Olschewski, Andrea; Wolff, Matthias; Bräu, Michael E; Hempelmann, Gunter; Vogel, Werner; Safronov, Boris V

2002-01-01

Combining the patch-clamp recordings in slice preparation with the ‘entire soma isolation' method we studied action of several local anaesthetics on delayed-rectifier K+ currents in spinal dorsal horn neurones.Bupivacaine, lidocaine and mepivacaine at low concentrations (1–100 μM) enhanced delayed-rectifier K+ current in intact neurones within the spinal cord slice, while exhibiting a partial blocking effect at higher concentrations (>100 μM). In isolated somata 0.1–10 μM bupivacaine enhanced delayed-rectifier K+ current by shifting its steady-state activation characteristic and the voltage-dependence of the activation time constant to more negative potentials by 10–20 mV.Detailed analysis has revealed that bupivacaine also increased the maximum delayed-rectifier K+ conductance by changing the open probability, rather than the unitary conductance, of the channel.It is concluded that local anaesthetics show a dual effect on delayed-rectifier K+ currents by potentiating them at low concentrations and partially suppressing at high concentrations. The phenomenon observed demonstrated the complex action of local anaesthetics during spinal and epidural anaesthesia, which is not restricted to a suppression of Na+ conductance only. PMID:12055132

An Evaluation of Dropouts from Outward Bound Programs for the Unemployed

ERIC Educational Resources Information Center

Maxwell, Robert; Perry, Martin; Martin, Andrew John

2008-01-01

Outward Bound New Zealand provides 21-day residential motivational intervention courses (Catalyst courses) to long-term unemployed clients approved by the Ministry of Social Development. During the period 2002/03, 20% of participants starting the course dropped out before course completion; which was double the contracted acceptable level set by…

Exploring Familial Relationship Growth and Negotiation: A Case Study of Outward Bound Family Courses

ERIC Educational Resources Information Center

Overholt, Jillisa R.

2013-01-01

This study explored the phenomenon of father-child relationship development within the context of an Outward Bound (OB) family course, an environment that may both disrupt the ordinary aspects of an established relationship, and provide activities to purposefully encourage relationship development through a variety of aspects inherent to the…

Academic Perspectives on the Outcomes of Outward Student Mobility

ERIC Educational Resources Information Center

Bridger, Kath

2015-01-01

This research project was commissioned by the UK Higher Education International Unit (IU) and the Higher Education Academy (HEA) in June 2014 to explore academic perspectives on the outcomes of outward mobility at undergraduate, postgraduate and research levels for UK domiciled students, and to consider how best to facilitate the take up as well…

Service at the Heart of Learning: Teachers' Writings.

ERIC Educational Resources Information Center

Cousins, Emily, Ed.; Mednick, Amy, Ed.

Expeditionary Learning Outward Bound (ELOB) is a framework for comprehensive school improvement that uses the philosophy and pedagogy of Outward Bound to make learning more hands-on, project-based, and adventurous. One of the 10 ELOB design principles is service and compassion. This book by teachers in ELOB schools contains accounts of students'…

Outward Bound Leadership Model: An Exploratory Study of Leadership Variables.

ERIC Educational Resources Information Center

Bartley, Natalie L.

A field study of 29 mountain-course instructors at the Colorado Outward Bound School (COBS) explored the relationships of gender-related personality traits and soft skills to outdoor leadership styles and course outcomes. Soft skills are competencies necessary for effective interpersonal helping skills, as opposed to hard skills, which are…

To Know By Experience: Outward Bound, North Carolina.

ERIC Educational Resources Information Center

Meyer, Dan; Meyer, Diane

Directed at discovering one's inner resources and the dignity of one's fellow man, the Outward Bound experience seeks to instill self-reliance, physical fitness, and compassion as fundamental values recognizing there are few opportunities to formulate such values in an increasingly technological and urbanized society. For 3 1/2 weeks, people from…

Classes in Courage

ERIC Educational Resources Information Center

Berger, Ron

2013-01-01

Renaissance School is part of a network of Expeditionary Learning (EL) schools that was borne of a collaboration between the Harvard Graduate School of Education and Outward Bound, USA. The EL model is centered on the Outward Bound ethic of having youth work together to achieve a task. EL schools take an approach to teaching and learning that…

Colorado Outward Bound School River Rafters' Manual.

ERIC Educational Resources Information Center

Leachman, Mark

Instructional sequences, safety rules, duties of crew members, and procedures for Colorado Outward Bound School river rafting trips are summarized in this manual. Designed to acquaint instructors with the duties expected of them on the trips, the information in the manual is presented in outline form and is intended for those with prior river…

The Influence of Anger Expression on Wound Healing

PubMed Central

Gouin, Jean-Philippe; Kiecolt-Glaser, Janice K.; Malarkey, William B.; Glaser, Ronald

2008-01-01

Certain patterns of anger expression have been associated with maladaptive alterations in cortisol secretion, immune functioning, and surgical recovery. We hypothesized that outward and inward anger expression and lack of anger control would be associated with delayed wound healing. A sample of 98 community-dwelling participants received standardized blister wounds on their non-dominant forearm. After blistering, the wounds were monitored daily for eight days to assess speed of repair. Logistic regression was used to distinguish fast and slow healers based on their anger expression pattern. Individuals exhibiting lower levels of anger control were more likely to be categorized as slow healers. The anger control variable predicted wound repair over and above differences in hostility, negative affectivity, social support, and health behaviors. Furthermore, participants with lower levels of anger control exhibited higher cortisol reactivity during the blistering procedure. This enhanced cortisol secretion was in turn related to longer time to heal. These findings suggest that the ability to regulate the expression of one’s anger has a clinically relevant impact on wound healing. PMID:18078737

Revealing an outward-facing open conformational state in a CLC Cl–/H+ exchange transporter

PubMed Central

Khantwal, Chandra M; Abraham, Sherwin J; Han, Wei; Jiang, Tao; Chavan, Tanmay S; Cheng, Ricky C; Elvington, Shelley M; Liu, Corey W; Mathews, Irimpan I; Stein, Richard A; Mchaourab, Hassane S; Tajkhorshid, Emad; Maduke, Merritt

2016-01-01

CLC secondary active transporters exchange Cl- for H+. Crystal structures have suggested that the conformational change from occluded to outward-facing states is unusually simple, involving only the rotation of a conserved glutamate (Gluex) upon its protonation. Using 19F NMR, we show that as [H+] is increased to protonate Gluex and enrich the outward-facing state, a residue ~20 Å away from Gluex, near the subunit interface, moves from buried to solvent-exposed. Consistent with functional relevance of this motion, constriction via inter-subunit cross-linking reduces transport. Molecular dynamics simulations indicate that the cross-link dampens extracellular gate-opening motions. In support of this model, mutations that decrease steric contact between Helix N (part of the extracellular gate) and Helix P (at the subunit interface) remove the inhibitory effect of the cross-link. Together, these results demonstrate the formation of a previously uncharacterized 'outward-facing open' state, and highlight the relevance of global structural changes in CLC function. DOI: http://dx.doi.org/10.7554/eLife.11189.001 PMID:26799336

Ceramic turbine stator vane and shroud support

DOEpatents

Glenn, Robert G.

1981-01-01

A support system for supporting the stationary ceramic vanes and ceramic outer shrouds which define the motive fluid gas path in a gas turbine engine is shown. Each individual segment of the ceramic component whether a vane or shroud segment has an integral radially outwardly projecting stem portion. The stem is enclosed in a split collet member of a high-temperature alloy material having a cavity configured to interlock with the stem portion. The generally cylindrical external surface of the collet engages a mating internal cylindrical surface of an aperture through a supporting arcuate ring segment with mating camming surfaces on the two facing cylindrical surfaces such that radially outward movement of the collet relative to the ring causes the internal cavity of the collet to be reduced in diameter to tightly engage the ceramic stem disposed therein. A portion of the collet extends outwardly through the ring segment opposite the ceramic piece and is threaded for receiving a nut and a compression washer for retaining the collet in the ring segment under a continuous biasing force urging the collet radially outwardly.

X-ray structures of LeuT in substrate-free outward-open and apo inward-open states

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

Krishnamurthy, Harini; Gouaux, Eric

2012-08-09

Neurotransmitter sodium symporters are integral membrane proteins that remove chemical transmitters from the synapse and terminate neurotransmission mediated by serotonin, dopamine, noradrenaline, glycine and GABA ({gamma}-aminobutyric acid). Crystal structures of the bacterial homologue, LeuT, in substrate-bound outward-occluded and competitive inhibitor-bound outward-facing states have advanced our mechanistic understanding of neurotransmitter sodium symporters but have left fundamental questions unanswered. Here we report crystal structures of LeuT mutants in complexes with conformation-specific antibody fragments in the outward-open and inward-open states. In the absence of substrate but in the presence of sodium the transporter is outward-open, illustrating how the binding of substrate closes themore » extracellular gate through local conformational changes: hinge-bending movements of the extracellular halves of transmembrane domains 1, 2 and 6, together with translation of extracellular loop 4. The inward-open conformation, by contrast, involves large-scale conformational changes, including a reorientation of transmembrane domains 1, 2, 5, 6 and 7, a marked hinge bending of transmembrane domain 1a and occlusion of the extracellular vestibule by extracellular loop 4. These changes close the extracellular gate, open an intracellular vestibule, and largely disrupt the two sodium sites, thus providing a mechanism by which ions and substrate are released to the cytoplasm. The new structures establish a structural framework for the mechanism of neurotransmitter sodium symporters and their modulation by therapeutic and illicit substances.« less

Differences in intersaccadic adaptation transfer between inward and outward adaptation.

PubMed

Schnier, Fabian; Lappe, Markus

2011-09-01

Saccadic adaptation is a mechanism to increase or decrease the amplitude gain of subsequent saccades, if a saccade is not on target. Recent research has shown that the mechanism of gain increasing, or outward adaptation, and the mechanism of gain decreasing, or inward adaptation, rely on partly different processes. We investigate how outward and inward adaptation of reactive saccades transfer to other types of saccades, namely scanning, overlap, memory-guided, and gap saccades. Previous research has shown that inward adaptation of reactive saccades transfers only partially to these other saccade types, suggesting differences in the control mechanisms between these saccade categories. We show that outward adaptation transfers stronger to scanning and overlap saccades than inward adaptation, and that the strength of transfer depends on the duration for which the saccade target is visible before saccade onset. Furthermore, we show that this transfer is mainly driven by an increase in saccade duration, which is apparent for all saccade categories. Inward adaptation, in contrast, is accompanied by a decrease in duration and in peak velocity, but only the peak velocity decrease transfers from reactive saccades to other saccade categories, i.e., saccadic duration remains constant or even increases for test saccades of the other categories. Our results, therefore, show that duration and peak velocity are independent parameters of saccadic adaptation and that they are differently involved in the transfer of adaptation between saccade categories. Furthermore, our results add evidence that inward and outward adaptation are different processes.

OUTWARD MIGRATION OF JUPITER AND SATURN IN 3:2 OR 2:1 RESONANCE IN RADIATIVE DISKS: IMPLICATIONS FOR THE GRAND TACK AND NICE MODELS

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

Pierens, Arnaud; Raymond, Sean N.; Nesvorny, David

Embedded in the gaseous protoplanetary disk, Jupiter and Saturn naturally become trapped in 3:2 resonance and migrate outward. This serves as the basis of the Grand Tack model. However, previous hydrodynamical simulations were restricted to isothermal disks, with moderate aspect ratio and viscosity. Here we simulate the orbital evolution of the gas giants in disks with viscous heating and radiative cooling. We find that Jupiter and Saturn migrate outward in 3:2 resonance in modest-mass (M {sub disk} ≈ M {sub MMSN}, where MMSN is the {sup m}inimum-mass solar nebula{sup )} disks with viscous stress parameter α between 10{sup –3} andmore » 10{sup –2}. In disks with relatively low-mass (M {sub disk} ≲ M {sub MMSN}), Jupiter and Saturn get captured in 2:1 resonance and can even migrate outward in low-viscosity disks (α ≤ 10{sup –4}). Such disks have a very small aspect ratio (h ∼ 0.02-0.03) that favors outward migration after capture in 2:1 resonance, as confirmed by isothermal runs which resulted in a similar outcome for h ∼ 0.02 and α ≤ 10{sup –4}. We also performed N-body runs of the outer solar system starting from the results of our hydrodynamical simulations and including 2-3 ice giants. After dispersal of the gaseous disk, a Nice model instability starting with Jupiter and Saturn in 2:1 resonance results in good solar systems analogs. We conclude that in a cold solar nebula, the 2:1 resonance between Jupiter and Saturn can lead to outward migration of the system, and this may represent an alternative scenario for the evolution of the solar system.« less

Hall Effect–Mediated Magnetic Flux Transport in Protoplanetary Disks

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

Bai, Xue-Ning; Stone, James M.

2017-02-10

The global evolution of protoplanetary disks (PPDs) has recently been shown to be largely controlled by the amount of poloidal magnetic flux threading the disk. The amount of magnetic flux must also coevolve with the disk, as a result of magnetic flux transport, a process that is poorly understood. In weakly ionized gas as in PPDs, magnetic flux is largely frozen in the electron fluid, except when resistivity is large. When the disk is largely laminar, we show that the relative drift between the electrons and ions (the Hall drift), and the ions and neutral fluids (ambipolar drift) can playmore » a dominant role on the transport of magnetic flux. Using two-dimensional simulations that incorporate the Hall effect and ambipolar diffusion (AD) with prescribed diffusivities, we show that when large-scale poloidal field is aligned with disk rotation, the Hall effect rapidly drags magnetic flux inward at the midplane region, while it slowly pushes flux outward above/below the midplane. This leads to a highly radially elongated field configuration as a global manifestation of the Hall-shear instability. This field configuration further promotes rapid outward flux transport by AD at the midplane, leading to instability saturation. In quasi-steady state, magnetic flux is transported outward at approximately the same rate at all heights, and the rate is comparable to the Hall-free case. For anti-aligned field polarity, the Hall effect consistently transports magnetic flux outward, leading to a largely vertical field configuration in the midplane region. The field lines in the upper layer first bend radially inward and then outward to launch a disk wind. Overall, the net rate of outward flux transport is about twice as fast as that of the aligned case. In addition, the rate of flux transport increases with increasing disk magnetization. The absolute rate of transport is sensitive to disk microphysics, which remains to be explored in future studies.« less

LASCO White-Light Observations of Eruptive Current Sheets Trailing CMEs

NASA Astrophysics Data System (ADS)

Webb, David F.; Vourlidas, Angelos

2016-12-01

Many models of eruptive flares or coronal mass ejections (CMEs) involve formation of a current sheet connecting the ejecting CME flux rope with a magnetic loop arcade. However, there is very limited observational information on the properties and evolution of these structures, hindering progress in understanding eruptive activity from the Sun. In white-light images, narrow coaxial rays trailing the outward-moving CME have been interpreted as current sheets. Here, we undertake the most comprehensive statistical study of CME-rays to date. We use SOHO/LASCO data, which have a higher cadence, larger field of view, and better sensitivity than any previous coronagraph. We compare our results to a previous study of Solar Maximum Mission (SMM) CMEs, in 1984 - 1989, having candidate magnetic disconnection features at the CME base, about half of which were followed by coaxial bright rays. We examine all LASCO CMEs during two periods of minimum and maximum activity in Solar Cycle 23, resulting in many more events, ˜130 CME-rays, than during SMM. Important results include: The occurrence rate of the rays is ˜11 % of all CMEs during solar minimum, but decreases to ˜7 % at solar maximum; this is most likely related to the more complex coronal background. The rays appear on average 3 - 4 hours after the CME core, and are typically visible for three-fourths of a day. The mean observed current sheet length over the ray lifetime is ˜12 R_{⊙}, with the longest current sheet of 18.5 R_{⊙}. The mean CS growth rates are 188 km s^{-1} at minimum and 324 km s^{-1} at maximum. Outward-moving blobs within several rays, which are indicative of reconnection outflows, have average velocities of ˜350 km s^{-1} with small positive accelerations. A pre-existing streamer is blown out in most of the CME-ray events, but half of these are observed to reform within ˜1 day. The long lifetime and long lengths of the CME-rays challenge our current understanding of the evolution of the magnetic field in the aftermath of CMEs.

Cell design for lithium alloy/metal sulfide battery

DOEpatents

Kaun, Thomas D.

1985-01-01

The disclosed lithium alloy/iron sulfide cell design provides loop-like positive and negative sheet metal current collectors electrically insulated from one another by separator means, the positive collector being located outwardly of the negative collector. The collectors are initially secured within an open-ended cell housing, which allows for collector pretesting for electrical shorts prior to adding any electrode materials and/or electrolyte to the cell. Separate chambers are defined outwardly of the positive collector and inwardly of the negative collector open respectively in opposite directions toward the open ends of the cell housing; and positive and negative electrode materials can be extruded into these respective chambers via the opposite open housing ends. The chambers and cell housing ends can then be sealed closed. A cross wall structurally reinforces the cell housing and also thereby defines two cavities, and paired positive and negative collectors are disposed in each cavity and electrically connected in parallel. The cell design provides for a high specific energy output and improved operating life in that any charge-discharge cycle swelling of the positive electrode material will be inwardly against only the positive collector to minimize shorts caused by the collectors shifting relative to one another.

Improved cell design for lithium alloy/metal sulfide battery

DOEpatents

Kaun, T.D.

1984-03-30

The disclosed lithium alloy/iron sulfide cell design provides loop-like positive and negative sheet metal current collectors electrically insulated from one another by separator means, the positive collector being located outwardly of the negative collector. The collectors are initially secured within an open-ended cell housing, which allows for collector pretesting for electrical shorts prior to adding any electrode materials and/or electrolyte to the cell. Separate chambers are defined outwardly of the positive collector and inwardly of the negative collector open respectively in opposite directions toward the open ends of the cell housing; and positive and negative electrode materials can be extruded into these respective chambers via the opposite open housing ends. The chambers and cell housing ends can then be sealed closed. A cross wall structurally reinforces the cell housing and also thereby defines two cavities, and paired positive and negative collectors are disposed in each cavity and electrically connected in parallel. The cell design provides for a high specific energy output and improved operating life in that any charge-discharge cycle swelling of the positive electrode material will be inwardly against only the positive collector to minimize shorts caused by the collectors shifting relative to one another.

Transient, Small-Scale Field-Aligned Currents in the Plasma Sheet Boundary Layer During Storm Time Substorms

NASA Technical Reports Server (NTRS)

Nakamura, R.; Sergeev, V. A.; Baumjohann, W.; Plaschke, F.; Magnes, W.; Fischer, D.; Varsani, A.; Schmid, D.; Nakamura, T. K. M.; Russell, C. T.;

Transient, small-scale field-aligned currents in the plasma sheet boundary layer during storm time substorms.

PubMed

Nakamura, R; Sergeev, V A; Baumjohann, W; Plaschke, F; Magnes, W; Fischer, D; Varsani, A; Schmid, D; Nakamura, T K M; Russell, C T; Strangeway, R J; Leinweber, H K; Le, G; Bromund, K R; Pollock, C J; Giles, B L; Dorelli, J C; Gershman, D J; Paterson, W; Avanov, L A; Fuselier, S A; Genestreti, K; Burch, J L; Torbert, R B; Chutter, M; Argall, M R; Anderson, B J; Lindqvist, P-A; Marklund, G T; Khotyaintsev, Y V; Mauk, B H; Cohen, I J; Baker, D N; Jaynes, A N; Ergun, R E; Singer, H J; Slavin, J A; Kepko, E L; Moore, T E; Lavraud, B; Coffey, V; Saito, Y

2016-05-28

We report on field-aligned current observations by the four Magnetospheric Multiscale (MMS) spacecraft near the plasma sheet boundary layer (PSBL) during two major substorms on 23 June 2015. Small-scale field-aligned currents were found embedded in fluctuating PSBL flux tubes near the separatrix region. We resolve, for the first time, short-lived earthward (downward) intense field-aligned current sheets with thicknesses of a few tens of kilometers, which are well below the ion scale, on flux tubes moving equatorward/earthward during outward plasma sheet expansion. They coincide with upward field-aligned electron beams with energies of a few hundred eV. These electrons are most likely due to acceleration associated with a reconnection jet or high-energy ion beam-produced disturbances. The observations highlight coupling of multiscale processes in PSBL as a consequence of magnetotail reconnection.

Adrenoceptor-Mediated Post- and Pre-Synaptic Regulations of the Reticulospinal Neurons in Rat Caudal Pontine Reticular Nucleus.

PubMed

Yang, Nian; Qiao, Qi-Cheng; Liu, Yu-Hui; Zhang, Ji-Qiang; Hu, Zhi-An; Zhang, Jun

2016-12-01

The central noradrenergic system participates in diverse nervous functions. Nevertheless, our knowledge of the action of adrenoceptors in motor regulation is still lacking. Intriguingly, reticulospinal neurons in the caudal pontine reticular nucleus (PnC) receive fairly dense noradrenergic innervation and play an important role in motor control. Here, after demonstrating the expression of α1- and α2-adrenoceptors in the PnC, we found that noradrenaline elicited a post-synaptic effect (inward or outward whole-cell current at -70 mV holding) on PnC reticulospinal neurons. The α1- and α2-adrenoceptors were co-expressed in individual PnC reticulospinal neurons to mediate an inward and an outward current component at -70 mV holding, respectively, which, when superposed, produced the overall post-synaptic effects of noradrenaline (NA). More importantly, the activation of post-synaptic α1- or α2-adrenoceptors indeed exerted opposing modulations (excitation vs. inhibition) on the firing activities of individual PnC reticulospinal neurons. Furthermore, the activation and inhibition of the Na + -permeable non-selective cationic conductance (NSCC) were demonstrated to be coupled to α1- and α2-adrenoceptors, respectively. Additionally, the activation of α2-adrenoceptors activated K + conductance. Pre-synaptically, the α2-adrenoceptors were expressed to attenuate the miniature excitatory postsynaptic current (mEPSC) in PnC reticulospinal neurons, but not to affect the miniature inhibitory postsynaptic current (mIPSC). Consistently, the evoked EPSC in PnC reticulospinal neurons was suppressed after the activation of pre-synaptic α2-adrenoceptors. Thus, the excitatory input and post-synaptic dynamics of PnC reticulospinal neurons are indeed intricately modulated by the activation of α1- and α2-adrenoceptors, through which motor control may be regulated in an adaptive manner by the central noradrenergic system.

Coupled low-energy - ring current plasma diffusion in the Jovian magnetosphere

NASA Technical Reports Server (NTRS)

Summers, D.; Siscoe, G. L.

1985-01-01

The outwardly diffusing Iogenic plasma and the simultaneously inwardly diffusing ring current plasma in the Jovian magnetosphere are described using a coupled diffusion model which incorporates the effects of the pressure gradient of the ring current into the cross-L diffusion coefficient. The coupled diffusion coefficient is derived by calculating the total energy available to drive the diffusion process. The condition is imposed that the diffusion coefficient takes on a local minimum value at some point in the region L = 7-8, at which point the gradient of the Io plasma density is specified as ramp value given by Siscoe et al. (1981). The hypothesis that the pressure gradient of the ring current causes the diminution of radial plasma transport is tested, and solution profiles for the Iogenic and ring current plasma densities are obtained which imply that the Io plasma ramp is caused by a high-density, low-energy component of the ring current hitherto unobserved directly.

ISEE-1 and 2 observations of field-aligned currents in the distant midnight magnetosphere

NASA Technical Reports Server (NTRS)

Elphic, R. C.; Kelly, T. J.; Russell, C. T.

1985-01-01

Magnetic field measurements obtained in the nightside magnetosphere by the co-orbiting ISEE-1 and 2 spacecraft have been examined for signatures of field-aligned currents (FAC). Such currents are found on the boundary of the plasma sheet both when the plasma sheet is expanding and when it is thinning. Evidence is often found for the existence of waves on the plasma sheet boundary, leading to multiple crossings of the FAC sheet. At times the boundary layer FAC sheet orientation is nearly parallel to the X-Z GSM plane, suggesting 'protrusions' of plasma sheet into the lobes. The boundary layer current polarity is, as expected, into the ionosphere in the midnight to dawn local time sector, and outward near dusk. Current sheet thicknesses and velocities are essentially independent of plasma sheet expansion or thinning, having typical values of 1500 km and 20-40 km/s respectively. Characteristic boundary layer current densities are about 10 nanoamps per square meter.

An Analysis of the Impact of Outward Bound on Twelve High Schools.

ERIC Educational Resources Information Center

Schulze, Joseph R.

Describing and analyzing the impact of Outward Bound (OB) programs on 12 high schools which reflect OB involvement varying from 1 to 5 years and include urban, suburban, and rural (public, private, boarding, and day) schools, this 1970-71 report is aimed at furthering OB philosophy and method. The report presents OB program: background; evaluation…

Outward Motions of SiO Masers around VX Sgr

NASA Astrophysics Data System (ADS)

Su, J. B.; Shen, Z.-Q.; Chen, X.; Jiang, D. R.

2014-09-01

We report the proper motions of SiO maser features around VX Sgr from the two-epoch VLBA observations (2006 December 15 and 2007 August 19). The majority of maser feature activities show a trend of outward motions. It is consistent with our previous finding that the outflow may play an important role for SiO maser pumping.

Outward Foreign Direct Investment and Human Capital Development: A Small Country Perspective

ERIC Educational Resources Information Center

McDonnell, Anthony

2008-01-01

Purpose: The purpose of this paper is to examine the pattern of outward foreign direct investment (FDI) by Irish MNCs, and more specifically, to investigate their approach to human capital development and how these correspond to foreign MNCs in Ireland. In particular, it seeks to investigate training and development expenditure, adoption of…

Participants' Perceptions of Their Outward Bound Final Expedition and the Relationship to Instructor Supervisory Position

ERIC Educational Resources Information Center

Bobilya, Andrew J.; Kalisch, Kenneth R.; Daniel, Brad

2014-01-01

The purpose of this mixed-method study was to understand participants' perceptions of their Outward Bound Final Expedition experience and more specifically the relationship between the instructor supervisory position and participant's perception of learning. A sample of 331 students consented to participate and completed a survey at the conclusion…

19 CFR 192.14 - Electronic information for outward cargo required in advance of departure.

Code of Federal Regulations, 2014 CFR

2014-04-01

... Information Through the Automated Export System (AES) § 192.14 Electronic information for outward cargo... Automated Export System (AES)). (b) Presentation of data—(1) Time for presenting data. USPPIs or their... regulatory authority to do so. The CBP will also continue to require 72-hour advance notice for used vehicle...

19 CFR 192.14 - Electronic information for outward cargo required in advance of departure.

Code of Federal Regulations, 2013 CFR

2013-04-01

... Information Through the Automated Export System (AES) § 192.14 Electronic information for outward cargo... Automated Export System (AES)). (b) Presentation of data—(1) Time for presenting data. USPPIs or their... regulatory authority to do so. The CBP will also continue to require 72-hour advance notice for used vehicle...

19 CFR 192.14 - Electronic information for outward cargo required in advance of departure.

Code of Federal Regulations, 2012 CFR

2012-04-01

... Information Through the Automated Export System (AES) § 192.14 Electronic information for outward cargo... Automated Export System (AES)). (b) Presentation of data—(1) Time for presenting data. USPPIs or their... regulatory authority to do so. The CBP will also continue to require 72-hour advance notice for used vehicle...

19 CFR 192.14 - Electronic information for outward cargo required in advance of departure.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Information Through the Automated Export System (AES) § 192.14 Electronic information for outward cargo... Automated Export System (AES)). (b) Presentation of data—(1) Time for presenting data. USPPIs or their... regulatory authority to do so. The CBP will also continue to require 72-hour advance notice for used vehicle...

An exploratory study of the changes in benefits sought during an outward bound experience

Treesearch

Frederick Kacprzynski

1992-01-01

Participants in an eight-day Outward Bound program were asked about their motivations for participation before the experience began and at the mid-point of the actual experience. Although more anticipated differences were expected, based on motivational theory, only one of the twelve motivational domains was significantly different at the .001 level.

Using Means-End Theory To Understand the Outdoor Adventure Experience.

ERIC Educational Resources Information Center

Goldenberg, Marni; Klenosky, David; McAvoy, Leo; Holman, Tom

Means-end analysis was used to examine the linkages between elements of an Outward Bound course and the personal benefits and outcomes obtained or reinforced by course completion. A self-administered questionnaire was completed by 216 persons, who completed a course at the North Carolina Outward Bound School. Respondents were aged 14-66 (83…

The Curious Shorelines of Gorgonum Chaos

NASA Technical Reports Server (NTRS)

Howard, A. D.; Moore, J. M.

2003-01-01

Level, bench-like platforms in the interior of the Gorgonum Chaos basin appear to be shorelines associated with an ancient lake. These shorelines, however, seem to lack the typical features of shorelines associated with wave and current transport and erosion, such as crescentic embayments, spits, barrier islands, and wave-cut cliffs. Rather, the lakefacing platform edges are commonly rounded and cumulate in planform, often evenly encircling presumed islands. We interpret these shorelines to have been formed by outward growth in a quiescent environment, possibly in ice-covered bodies of water and possibly, in part, as chemical precipitates.

Centaurus A galaxy, type EO peculiar elliptical, also radio source

NASA Technical Reports Server (NTRS)

2002-01-01

Centaurus A galaxy, type EO peculiar elliptical, also radio source. CTIO 4-meter telescope, 1975. NGC 5128, a Type EO peculiar elliptical galaxy in the constellation Centaurus. This galaxy is one of the most luminous and massive galaxies known and is a strong source of both radio and X-ray radiation. Current theories suggest that the nucleus is experiencing giant explosions involving millions of stars and that the dark band across the galactic disk is material being ejected outward. Cerro Toloto 4-meter telescope photo. Photo credit: National Optical Astronomy Observatories

Characteristics of the NASA Lewis bumpy torus plasma generated with high positive or negative applied potentials

NASA Technical Reports Server (NTRS)

Roth, J. R.; Gerdin, G. A.

1976-01-01

The toroidal ring of plasma contained in the NASA Lewis bumpy-torus superconducting magnet facility may be biased to positive or negative potentials approaching 50 kilovolts by applying direct-current voltages of the respective polarity to 12 or fewer of the midplane electrode rings. The electric fields which are responsible for heating the ions by E/B drift then point radially outward or inward. The low-frequency fluctuations below the ion cyclotron frequency appeared to be dominated by rotating spokes.

Tokamak with in situ magnetohydrodynamic generation of toroidal magnetic field

DOEpatents

Schaffer, Michael J.

1986-01-01

A tokamak apparatus includes an electrically conductive metal pressure vessel for defining a chamber and confining liquid therein. A liner disposed within said chamber defines a toroidal space within the liner and confines gas therein. The metal vessel provides an electrically conductive path linking the toroidal space. Liquid metal is forced outwardly through the chamber outside of the toroidal space to generate electric current in the conductive path and thereby generate a toroidal magnetic field within the toroidal space. Toroidal plasma is developed within the toroidal space about the major axis thereof.

Synaptic Mechanisms of Action of Convulsion-Producing Anticholinesterases. Characterization of Di-Isopropyl Phosphorofluoridate-Induced Epileptiform Activity in the Mammalian Hippocampus.

DTIC Science & Technology

1983-10-01

O ) OV6 ISOBSLET *SECURITY CLASSIFICATION OF THIS PAGE (Oc~ Dt. Entered) - 4 .. I,3...* %%S& P 4. A I IUN U ,13 ’ A ^II t~,.. I. f ltnew- A "viously...Abstr. 8:558, 1982. 73. Gustafsson, B., Galvan, M., Grafe, P . and Wigstrom, H. A transient outward current in a mammalian central neurone blocked by 4...TEST CHART N4ATIONAL BUREAU CF STANAROS -963 - A ............ ............ AD _ _ _ Report No. 1 SYNAPTIC MECHANISMS OF ACTION OF CONVULSION-PRODUCING

Low voltage nonprimary explosive detonator

DOEpatents

Dinegar, Robert H.; Kirkham, John

1982-01-01

A low voltage, electrically actuated, nonprimary explosive detonator is disclosed wherein said detonation is achieved by means of an explosive train in which a deflagration-to-detonation transition is made to occur. The explosive train is confined within a cylindrical body and positioned adjacent to low voltage ignition means have electrical leads extending outwardly from the cylindrical confining body. Application of a low voltage current to the electrical leads ignites a self-sustained deflagration in a donor portion of the explosive train which then is made to undergo a transition to detonation further down the train.

NGC 4622:. A clear example of spiral density wave star formation unused in textbooks.

NASA Astrophysics Data System (ADS)

Byrd, Gene G.

2018-06-01

Refer to the poster HST images or to http://heritage.stsci.edu/2002/03/index.html. The top northeastern (NE) arm of NGC 4622 winds outward clockwise (CW) showing beautiful “ beads on a string” blue stellar associations on the CONCAVE SIDE of the arm. These are nicely offset CW in position from the density concentration of old yellow stars in the arms. The displacement would result from aggregation of gas clouds as they orbit CW into a more slowly turning stellar disk arm pattern. There is a time delay until the associations form and light up on the concave side. Farther inward along the top NE arm, the lit-up associations occur in the MIDDLE of the stellar arm. This is characteristic of the co-rotation (CR) radius where the CW orbital angular rate of the gas clouds and the arm CW pattern speeds match. Just within CR, the association displacement from the stellar arm is opposite (CCW) onto the CONVEX SIDE of the arm. A similar displacement sequence from concave (outside CR), middle (at CR) to convex (inside CR) is seen along the lower southwestern arm. Why isn’t NGC 4622 featured in textbooks? A rather puzzling single stellar arm winds outward CCW from the center, opposite to the outer pair. The eastern edge of the disk (marked by dust cloud silhouettes) is the nearer edge. The NE portion radial velocity is away relative to the nucleus so the disk orbital motion is CW. The outer pair of arms thus winds outward to LEAD in the same direction as the CW orbital motion, contrary to typical arm winding. Actually, the leading pair of arms and single inner arm would make NGC 4622 even better for use in introductory astronomy texts. Students can debate the origin of this galaxy's strange arm pattern which, ironically, matches density wave predictions so well. This is better than simply reading a textbook and thinking that all is explained. See G. G. Byrd; T. Freeman; S. Howard; R. J. Buta (2008). Astron. J., 135, p. 408–413 and references there for observations and hypotheses about NGC 4622’s arms. This work was supported by NSAS/STScI grant 8707 to the Univ. of Alabama and NSF grant AST 02-0177 to Bevill State College, Fayette, AL. Also see https://www.researchgate.net/profile/Gene_Byrd2

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.

Ionic currents of outer hair cells isolated from the guinea-pig cochlea.

PubMed

Housley, G D; Ashmore, J F

1992-03-01

1. Whole-cell currents were measured in outer hair cells isolated from each turn of the organ of Corti of the guinea-pig. 2. The slope input conductances at -70 mV of the cells ranged from 3.6 to 51 nS depending on the length of the cell. Shorter cells from the basal turns of the cochlea had the highest values. The membrane time constant of the cells varied from 3 to 0.2 ms from the apex to the base. 3. Irrespective of the position of the cells along the cochlea, three distinct currents were found. Each type of current was found in approximately the same proportion in all cells. 4. An outward K+ current was present which activated at potentials more positive than -35 mV. The current was sensitive to tetraethylammonium (30 mM), quinidine (100 microM) and nifedipine (50 microM). It could be removed by replacing external Ca2+ with Ba2+ or Mg2+. The current was also removed by substituting Nai+ or Csi+ for Ki+ pipette solution. This outwardly rectifying current appears similar to the calcium-activated K+ current described in other hair cells. 5. The main current present at membrane potentials from -90 mV to -50 mV was a second voltage-activated K+ current. It was 50% activated at -80 mV, and relaxed with a time constant of 20-40 ms on hyperpolarization to -120 mV. Near rest the kinetics were essentially time-dependent , but depended upon the external K+ concentration. The current was blocked by 5 mM external Cs+. 6. This current was highly selective for K+. Measured from reversal of the tail currents, the permeability ratio PK:PNa was approximately 30:1. Depolarization of the cell, presumed to lead to an elevation of intracellular calcium, produced a prolonged activation of the current. 7. A third current found in the cells was a cation current. By external ion replacement, the selectivity sequence was determined to be Ca2+ greater than Na+ approximately equal to K+ greater than choline+ greater than NMDG+ (respective permeabilities relative to Na: 2.9, 1.0, 0.99, 0.63 and 0.37). This current was reduced by external Ba2+ (3 mM) and by nifedipine (50 microM). The activation of this current appeared to depend upon raised levels of Cai2+. 8. These currents account for reported in vivo properties of cochlear outer hair cells as cells permeable to potassium at large negative resting potentials. The consequences for sound detection in the cochlea are briefly discussed.

Cultivating Environmental Virtue among 7th and 8th Graders in an Expeditionary Learning Outward Bound School

ERIC Educational Resources Information Center

Martin, Bruce; Bright, Alan; Cafaro, Philip; Mittelstaedt, Robin; Bruyere, Brett

2008-01-01

This study attempted to assess the development of environmental virtue in 7th and 8th grade students in an Expeditionary Learning Outward Bound school. The purpose of this study was twofold. First, the researchers were interested in introducing a virtue ethics perspective into their teaching of environmental ethics. Second, the researchers were…

City Kids in the Wilderness: A Pilot-Test of Outward Bound for Foster Care Group Home Youth.

ERIC Educational Resources Information Center

Fischer, Robert L.; Attah, E. B.

2001-01-01

A study examined perceptions of a 7-day Outward Bound program among 23 urban youths, foster parents, and foster care workers from group homes in Atlanta (Georgia). Foster parents reported improved self-esteem and behavior among the teens, but foster care workers reported worse behavior. Negative program impressions lessened among male youths but…

Reactive solid surface morphology variation via ionic diffusion.

PubMed

Sun, Zhenchao; Zhou, Qiang; Fan, Liang-Shih

2012-08-14

In gas-solid reactions, one of the most important factors that determine the overall reaction rate is the solid morphology, which can be characterized by a combination of smooth, convex and concave structures. Generally, the solid surface structure varies in the course of reactions, which is classically noted as being attributed to one or more of the following three mechanisms: mechanical interaction, molar volume change, and sintering. Here we show that if a gas-solid reaction involves the outward ionic diffusion of a solid-phase reactant then this outward ionic diffusion could eventually smooth the surface with an initial concave and/or convex structure. Specifically, the concave surface is filled via a larger outward diffusing surface pointing to the concave valley, whereas the height of the convex surface decreases via a lower outward diffusion flux in the vertical direction. A quantitative 2-D continuum diffusion model is established to analyze these two morphological variation processes, which shows consistent results with the experiments. This surface morphology variation by solid-phase ionic diffusion serves to provide a fourth mechanism that supplements the traditionally acknowledged solid morphology variation or, in general, porosity variation mechanisms in gas-solid reactions.

All dressed up but nowhere to go? Delayed hospital discharges and older people.

PubMed

Glasby, Jon; Littlechild, Rosemary; Pryce, Kathryn

2006-01-01

Delayed hospital discharges are a key concern in a number of industrialized nations and are the subject of a range of government initiatives in the English National Health Service. The aim of this paper was to review the UK literature on delayed hospital discharges and older people in order to identify and explore the rate and causes of delayed hospital discharges, together with policies and practices that may reduce delayed discharges and improve the experiences of older people. Literature review based on searches of major health/social-care databases. Sources which explore the rate and cause of delayed discharges in the UK were included. Relevant documents were categorized using the research hierarchy set out in the National Service Framework for Older People and analysed according to criteria for appraising the quality of qualitative research proposed by Mays et al. The review identified 21 studies, which suggest very different rates and causes of delayed discharge in different settings. The studies reveal the importance of rehabilitation services to reduce the rate of delayed discharge, the prevalence of delayed discharges caused by internal hospital factors, and the complex and multi-faceted nature of the factors contributing to delayed discharge. Despite this, the studies have a number of methodological flaws and often fail to include a patient perspective or to consider detailed policies and approaches to reduce the number of delayed discharges. There is also a failure to consider the needs of older people with mental health problems or people from minority ethnic communities. The evidence, as it currently stands, raises a number of issues about current hospital discharge policy, supporting some aspects of the current government agenda in England, but questioning other aspects.

Antisense oligonucleotides suppress cell-volume-induced activation of chloride channels.

PubMed

Gschwentner, M; Nagl, U O; Wöll, E; Schmarda, A; Ritter, M; Paulmichl, M

1995-08-01

Cell volume regulation is an essential feature of most cells. After swelling in hypotonic media, the simultaneous activation of potassium and chloride channels is believed to be the initial, time-determining step in cell volume regulation. The activation of both pathways is functionally linked and enables the cells to lose ions and water, subsequently leading to cell shrinkage and readjustment of the initial volume. NIH 3T3 fibroblasts efficiently regulate their volume after swelling and bear chloride channels that are activated by decreasing extracellular osmolarity. The chloride current elicited in these cells after swelling is reminiscent of the current found in oocytes expressing an outwardly rectifying chloride current termed ICln. Introduction of antisense oligodeoxynucleotides complementary to the first 30 nucleotides of the coding region of the ICln channel into NIH 3T3 fibroblasts suppresses the activation of the swelling-induced chloride current. The experiments directly demonstrate an unambiguous link between a volume-activated chloride current and a cloned protein involved in chloride transport.

[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.

Evidence for Two Separate Heliospheric Current Sheets of Cylindrical Shape During Mid-2012

NASA Astrophysics Data System (ADS)

Wang, Y.-M.; Young, P. R.; Muglach, K.

2014-01-01

During the reversal of the Sun's polar fields at sunspot maximum, outward extrapolations of magnetograph measurements often predict the presence of two or more current sheets extending into the interplanetary medium, instead of the single heliospheric current sheet (HCS) that forms the basis of the standard "ballerina skirt" picture. By comparing potential-field source-surface models of the coronal streamer belt with white-light coronagraph observations, we deduce that the HCS was split into two distinct structures with circular cross sections during mid-2012. These cylindrical current sheets were centered near the heliographic equator and separated in longitude by roughly 180° a corresponding four-sector polarity pattern was observed at Earth. Each cylinder enclosed a negative-polarity coronal hole that was identifiable in extreme ultraviolet images and gave rise to a high-speed stream. The two current sheet systems are shown to be a result of the dominance of the Sun's nonaxisymmetric quadrupole component, as the axial dipole field was undergoing its reversal during solar cycle 24.

Evidence for Two Separate Heliospheric Current Sheets of Cylindrical Shape During Mid-2012

NASA Technical Reports Server (NTRS)

Wang, Y.-M.; Young, P. R.; Muglach, K.

2013-01-01

During the reversal of the Sun's polar fields at sunspot maximum, outward extrapolations of magnetograph measurements often predict the presence of two or more current sheets extending into the interplanetary medium, instead of the single heliospheric current sheet (HCS) that forms the basis of the standard 'ballerina skirt' picture. By comparing potential-field source-surface models of the coronal streamer belt with white-light coronagraph observations, we deduce that the HCS was split into two distinct structures with circular cross sections during mid-2012. These cylindrical current sheets were centered near the heliographic equator and separated in longitude by roughly 180 deg; a corresponding four-sector polarity pattern was observed at Earth. Each cylinder enclosed a negative-polarity coronal hole that was identifiable in extreme ultraviolet images and gave rise to a high-speed stream. The two current sheet systems are shown to be a result of the dominance of the Sun's nonaxisymmetric quadrupole component, as the axial dipole field was undergoing its reversal during solar cycle 24.

Neuroanatomy of Individual Differences in Language in Adult Males with Autism

PubMed Central

Lai, Meng-Chuan; Lombardo, Michael V.; Ecker, Christine; Chakrabarti, Bhismadev; Suckling, John; Bullmore, Edward T.; Happé, Francesca; Murphy, Declan G. M.; Baron-Cohen, Simon

2015-01-01

One potential source of heterogeneity within autism spectrum conditions (ASC) is language development and ability. In 80 high-functioning male adults with ASC, we tested if variations in developmental and current structural language are associated with current neuroanatomy. Groups with and without language delay differed behaviorally in early social reciprocity, current language, but not current autistic features. Language delay was associated with larger total gray matter (GM) volume, smaller relative volume at bilateral insula, ventral basal ganglia, and right superior, middle, and polar temporal structures, and larger relative volume at pons and medulla oblongata in adulthood. Despite this heterogeneity, those with and without language delay showed significant commonality in morphometric features when contrasted with matched neurotypical individuals (n = 57). In ASC, better current language was associated with increased GM volume in bilateral temporal pole, superior temporal regions, dorsolateral fronto-parietal and cerebellar structures, and increased white matter volume in distributed frontal and insular regions. Furthermore, current language–neuroanatomy correlation patterns were similar across subgroups with or without language delay. High-functioning adult males with ASC show neuroanatomical variations associated with both developmental and current language characteristics. This underscores the importance of including both developmental and current language as specifiers for ASC, to help clarify heterogeneity. PMID:25249409

Changes in the action potential and transient outward potassium current in cardiomyocytes during acute cardiac rejection in rats.

PubMed

Luo, Wenqi; Jia, Yixin; Zheng, Shuai; Li, Yan; Han, Jie; Meng, Xu

2017-01-01

Acute cardiac rejection contributes to the changes in the electrophysiological properties of grafted hearts. However, the electrophysiological changes of cardiomyocytes during acute cardiac rejection are still unknown. An understanding of the electrophysiological mechanisms of cardiomyocytes could improve the diagnosis and treatment of acute cardiac rejection. So it is important to characterize the changes in the action potential ( AP ) and the transient outward potassium current ( I to ) in cardiomyocytes during acute cardiac rejection. Heterotopic heart transplantation was performed in allogeneic [Brown Norway (BN)-to-Lewis] and isogeneic (BN-to-BN) rats. Twenty models were established in each group. Ten recipients were sacrificed at the 2nd day and the other ten recipients were sacrificed at the 4 th day after the operation in each group. Histopathological examinations of the grafted hearts were performed in half of the recipients in each group randomly. The other half of the grafted hearts were excised rapidly and enzymatically dissociated to obtain single cardiomyocytes. The AP and I to current were recorded using the whole cell patch-clamp technique. Forty grafted hearts were successfully harvested and used in experiments. Histologic examination showed mild rejection at the 2 nd day and moderate rejection at the 4 th day in the allogeneic group after cardiac transplantation, while no evidence of histologic lesions of rejection were observed in the isogeneic group. Compared with the isogeneic group, the action potential duration ( APD ) of cardiomyocytes in the allogeneic group was significantly prolonged ( APD 90 was 49.28±5.621 mV in the isogeneic group and 88.08±6.445 mV in the allogeneic group at the 2 nd day, P=0.0016; APD 90 was 59.34±5.183 mV in the isogeneic group and 104.0±9.523 mV in the allogeneic group at the 4 th day, P=0.0064). The current density of I to was significantly decreased at the 4 th day after cardiac transplantation. The APD of cardiomyocytes was significantly prolonged during acute cardiac rejection in rats, which might be partly attributed to decreased current densities of I to .

K+ currents underlying the action of endothelium-derived hyperpolarizing factor in guinea-pig, rat and human blood vessels

PubMed Central

Coleman, H A; Tare, Marianne; Parkington, Helena C

2001-01-01

Membrane currents attributed to endothelium-derived hyperpolarizing factor (EDHF) were recorded in short segments of submucosal arterioles of guinea-pigs using single microelectrode voltage clamp. The functional responses of arterioles and human subcutaneous, rat hepatic and guinea-pig coronary arteries were also assessed as changes in membrane potential recorded simultaneously with contractile activity. The current-voltage (I-V) relationship for the conductance due to EDHF displayed outward rectification with little voltage dependence. Components of the current were blocked by charybdotoxin (30-60 nM) and apamin (0.25-0.50 μM), which also blocked hyperpolarization and prevented EDHF-induced relaxation. The EDHF-induced current was insensitive to Ba2+ (20-100 μM) and/or ouabain (1 μM to 1 mM). In human subcutaneous arteries and guinea-pig coronary arteries and submucosal arterioles, the EDHF-induced responses were insensitive to Ba2+ and/or ouabain. Increasing [K+]o to 11-21 mM evoked depolarization under conditions in which EDHF evoked hyperpolarization. Responses to ACh, sympathetic nerve stimulation and action potentials were indistinguishable between dye-labelled smooth muscle and endothelial cells in arterioles. Action potentials in identified endothelial cells were always associated with constriction of the arterioles. 18β-Glycyrrhetinic acid (30 μM) and carbenoxolone (100 μM) depolarized endothelial cells by 31 ± 6 mV (n = 7 animals) and 33 ± 4 mV (n = 5), respectively, inhibited action potentials in smooth muscle and endothelial cells and reduced the ACh-induced hyperpolarization of endothelial cells by 56 and 58 %, respectively. Thus, activation of outwardly rectifying K+ channels underlies the hyperpolarization and relaxation due to EDHF. These channels have properties similar to those of intermediate conductance (IKCa) and small conductance (SKCa) Ca2+-activated K+ channels. Strong electrical coupling between endothelial and smooth muscle cells implies that these two layers function as a single electrical syncytium. The non-specific effects of glycyrrhetinic acid precludes its use as an indicator of the involvement of gap junctions in EDHF-attributed responses. These conclusions are likely to apply to a variety of blood vessels including those of humans. PMID:11230509

An EP2 Agonist Facilitates NMDA-Induced Outward Currents and Inhibits Dendritic Beading through Activation of BK Channels in Mouse Cortical Neurons

PubMed Central

Hayashi, Yoshinori; Morinaga, Saori; Liu, Xia; Zhang, Jing; Wu, Zhou; Yokoyama, Takeshi; Nakanishi, Hiroshi

2016-01-01

Prostaglandin E2 (PGE2), a major metabolite of arachidonic acid produced by cyclooxygenase pathways, exerts its bioactive responses by activating four E-prostanoid receptor subtypes, EP1, EP2, EP3, and EP4. PGE2 enables modulating N-methyl-D-aspartate (NMDA) receptor-mediated responses. However, the effect of E-prostanoid receptor agonists on large-conductance Ca2+-activated K+ (BK) channels, which are functionally coupled with NMDA receptors, remains unclear. Here, we showed that EP2 receptor-mediated signaling pathways increased NMDA-induced outward currents (I NMDA-OUT), which are associated with the BK channel activation. Patch-clamp recordings from the acutely dissociated mouse cortical neurons revealed that an EP2 receptor agonist activated I NMDA-OUT, whereas an EP3 receptor agonist reduced it. Agonists of EP1 or EP4 receptors showed no significant effects on I NMDA-OUT. A direct perfusion of 3,5′-cyclic adenosine monophosphate (cAMP) through the patch pipette facilitated I NMDA-OUT, which was abolished by the presence of protein kinase A (PKA) inhibitor. Furthermore, facilitation of I NMDA-OUT caused by an EP2 receptor agonist was significantly suppressed by PKA inhibitor. Finally, the activation of BK channels through EP2 receptors facilitated the recovery phase of NMDA-induced dendritic beading in the primary cultured cortical neurons. These results suggest that a direct activation of BK channels by EP2 receptor-mediated signaling pathways plays neuroprotective roles in cortical neurons. PMID:27298516

Signaling of pigment-dispersing factor (PDF) in the Madeira cockroach Rhyparobia maderae.

PubMed

Wei, Hongying; Yasar, Hanzey; Funk, Nico W; Giese, Maria; Baz, El-Sayed; Stengl, Monika

2014-01-01

The insect neuropeptide pigment-dispersing factor (PDF) is a functional ortholog of vasoactive intestinal polypeptide, the coupling factor of the mammalian circadian pacemaker. Despite of PDF's importance for synchronized circadian locomotor activity rhythms its signaling is not well understood. We studied PDF signaling in primary cell cultures of the accessory medulla, the circadian pacemaker of the Madeira cockroach. In Ca²⁺ imaging studies four types of PDF-responses were distinguished. In regularly bursting type 1 pacemakers PDF application resulted in dose-dependent long-lasting increases in Ca²⁺ baseline concentration and frequency of oscillating Ca²⁺ transients. Adenylyl cyclase antagonists prevented PDF-responses in type 1 cells, indicating that PDF signaled via elevation of intracellular cAMP levels. In contrast, in type 2 pacemakers PDF transiently raised intracellular Ca²⁺ levels even after blocking adenylyl cyclase activity. In patch clamp experiments the previously characterized types 1-4 could not be identified. Instead, PDF-responses were categorized according to ion channels affected. Application of PDF inhibited outward potassium or inward sodium currents, sometimes in the same neuron. In a comparison of Ca²⁺ imaging and patch clamp experiments we hypothesized that in type 1 cells PDF-dependent rises in cAMP concentrations block primarily outward K⁺ currents. Possibly, this PDF-dependent depolarization underlies PDF-dependent phase advances of pacemakers. Finally, we propose that PDF-dependent concomitant modulation of K⁺ and Na⁺ channels in coupled pacemakers causes ultradian membrane potential oscillations as prerequisite to efficient synchronization via resonance.

Secular Evolution of Spiral Galaxies

DTIC Science & Technology

2003-01-01

recombination (z=1000). Furthermore, the BigBang nucleosynthesis model also requires a signi cantamount of non- baryonic dark matter (Primack 1999) ifthe universe...momentum (as well as energy) outward. Associ-ated with this outward angular momentum transport isan expected secular redistribution of disk matter , co...mode, a secular transfer of energy andangular momentum between the disk matter and thedensity wave. The existence of the phase shift betweenthe

A Comparison of Recidivism Rates for Operation Outward Reach (OOR) Participants and Control Groups of Non-Participants for the Years 1990 through 1994.

ERIC Educational Resources Information Center

Ryan, Thomas P.; Desuta, Joesph F.

2000-01-01

A 5-year study of Operation Outward Reach, a nonprofit program providing community-based vocational training in carpentry and masonry for Pennsylvania inmates, compared completers and control groups. Results showed average differences in recidivism between the groups of 16% per year. Fiscal and social cost savings were also identified. (JOW)

Outward Bound in the Professional Education of Teachers. A Study of an Experimental Component in Field Experiences.

ERIC Educational Resources Information Center

Smathers, Keener M.

In an effort to measure the impact of Outward Bound (OB) education on teacher candidates, an 18-day stress experience was arranged for 12 Appalachian State University students and then compared with the effects of the normal 11-week student teacher experiences of two other groups. The OB group underwent a series of individual and group wilderness…

Mechanisms of Firing Patterns in Fast-Spiking Cortical Interneurons

PubMed Central

Golomb, David; Donner, Karnit; Shacham, Liron; Shlosberg, Dan; Amitai, Yael; Hansel, David

2007-01-01

Cortical fast-spiking (FS) interneurons display highly variable electrophysiological properties. Their spike responses to step currents occur almost immediately following the step onset or after a substantial delay, during which subthreshold oscillations are frequently observed. Their firing patterns include high-frequency tonic firing and rhythmic or irregular bursting (stuttering). What is the origin of this variability? In the present paper, we hypothesize that it emerges naturally if one assumes a continuous distribution of properties in a small set of active channels. To test this hypothesis, we construct a minimal, single-compartment conductance-based model of FS cells that includes transient Na+, delayed-rectifier K+, and slowly inactivating d-type K+ conductances. The model is analyzed using nonlinear dynamical system theory. For small Na+ window current, the neuron exhibits high-frequency tonic firing. At current threshold, the spike response is almost instantaneous for small d-current conductance, g d, and it is delayed for larger g d. As g d further increases, the neuron stutters. Noise substantially reduces the delay duration and induces subthreshold oscillations. In contrast, when the Na+ window current is large, the neuron always fires tonically. Near threshold, the firing rates are low, and the delay to firing is only weakly sensitive to noise; subthreshold oscillations are not observed. We propose that the variability in the response of cortical FS neurons is a consequence of heterogeneities in their g d and in the strength of their Na+ window current. We predict the existence of two types of firing patterns in FS neurons, differing in the sensitivity of the delay duration to noise, in the minimal firing rate of the tonic discharge, and in the existence of subthreshold oscillations. We report experimental results from intracellular recordings supporting this prediction. PMID:17696606

Mechanisms of firing patterns in fast-spiking cortical interneurons.

PubMed

Golomb, David; Donner, Karnit; Shacham, Liron; Shlosberg, Dan; Amitai, Yael; Hansel, David

2007-08-01

Cortical fast-spiking (FS) interneurons display highly variable electrophysiological properties. Their spike responses to step currents occur almost immediately following the step onset or after a substantial delay, during which subthreshold oscillations are frequently observed. Their firing patterns include high-frequency tonic firing and rhythmic or irregular bursting (stuttering). What is the origin of this variability? In the present paper, we hypothesize that it emerges naturally if one assumes a continuous distribution of properties in a small set of active channels. To test this hypothesis, we construct a minimal, single-compartment conductance-based model of FS cells that includes transient Na(+), delayed-rectifier K(+), and slowly inactivating d-type K(+) conductances. The model is analyzed using nonlinear dynamical system theory. For small Na(+) window current, the neuron exhibits high-frequency tonic firing. At current threshold, the spike response is almost instantaneous for small d-current conductance, gd, and it is delayed for larger gd. As gd further increases, the neuron stutters. Noise substantially reduces the delay duration and induces subthreshold oscillations. In contrast, when the Na(+) window current is large, the neuron always fires tonically. Near threshold, the firing rates are low, and the delay to firing is only weakly sensitive to noise; subthreshold oscillations are not observed. We propose that the variability in the response of cortical FS neurons is a consequence of heterogeneities in their gd and in the strength of their Na(+) window current. We predict the existence of two types of firing patterns in FS neurons, differing in the sensitivity of the delay duration to noise, in the minimal firing rate of the tonic discharge, and in the existence of subthreshold oscillations. We report experimental results from intracellular recordings supporting this prediction.

Examination of a Regressive Prompt-Delay Procedure for Improving Sight-Word Reading

ERIC Educational Resources Information Center

Daly, Edward J., III.; Hess, Polly M.; Sommerhalder, Mackenzie; Strong, Whitney; Johnsen, Mallory; O'Connor, Maureen A.; Young, Nicholas D.

2016-01-01

The current two-experiment study examined the effects of a regressive prompt-delay procedure on sight-word reading of four elementary school students. In contrast to traditional progressive prompt-delay procedures in which the latency of prompts is increased, the regressive prompt-delay latency is decreased over time. Data indicate that…

Bi-frontal direct current stimulation affects delay discounting choices.

PubMed

Hecht, David; Walsh, Vincent; Lavidor, Michal

2013-01-01

In delay discounting tasks, participants decide between receiving a certain amount of money now or a larger sum sometime in the future. This study investigated the effects of transcranial direct current stimulation on delay discounting. Participants made delay discounting choices while receiving a bi-frontal stimulation of right-hemisphere anodal/left-hemisphere cathodal, left-hemisphere anodal/right-hemisphere cathodal, and sham stimulation, in three separate sessions. When the difference between the alternatives was 10% or more, participants generally preferred to wait for the larger sum. Nevertheless, there were more choices of smaller "immediate" gains, instead of the larger delayed options, when the left dorsolateral prefrontal cortex (DLPFC) was facilitated and the right DLPFC inhibited, compared to the sham stimulation. These observations indicate the significant role of the prefrontal cortex in delay discounting choices, and demonstrate that increased left frontal activation combined with decreased right frontal activation can alter decision-making by intensifying a tendency to choose immediate gains.

An analog integrated circuit beamformer for high-frequency medical ultrasound imaging.

PubMed

Gurun, Gokce; Zahorian, Jaime S; Sisman, Alper; Karaman, Mustafa; Hasler, Paul E; Degertekin, F Levent

2012-10-01

We designed and fabricated a dynamic receive beamformer integrated circuit (IC) in 0.35-μm CMOS technology. This beamformer IC is suitable for integration with an annular array transducer for high-frequency (30-50 MHz) intravascular ultrasound (IVUS) imaging. The beamformer IC consists of receive preamplifiers, an analog dynamic delay-and-sum beamformer, and buffers for 8 receive channels. To form an analog dynamic delay line we designed an analog delay cell based on the current-mode first-order all-pass filter topology, as the basic building block. To increase the bandwidth of the delay cell, we explored an enhancement technique on the current mirrors. This technique improved the overall bandwidth of the delay line by a factor of 6. Each delay cell consumes 2.1-mW of power and is capable of generating a tunable time delay between 1.75 ns to 2.5 ns. We successfully integrated the fabricated beamformer IC with an 8-element annular array. Experimental test results demonstrated the desired buffering, preamplification and delaying capabilities of the beamformer.

Effects of Replacement of External Sodium Chloride with Sucrose on Membrane Currents of the Squid Giant Axon

PubMed Central

Adelman, William J.; Taylor, Robert E.

1964-01-01

It was observed that a reduction of the sodium chloride concentration in the external solution bathing a squid giant axon by replacement with sucrose resulted in marked decreases in the peak inward and steady-state outward currents through the axon membrane following a step decrease in membrane potential. These effects are quantitatively acounted for by the increase in series resistance resulting from the decreased conductivity of the sea water and the assumption that the sodium current obeys a relation of the form I = k1C1 - k2C2 where C1, C2 are internal and external ion activities and k1, k2 are independent of concentration. It is concluded that the potassium ion current is independent of the sodium concentration. That the inward current is carried by sodium ions has been confirmed. The electrical potential (or barrier height) profile in the membrane which drives sodium ions appears to be independent of sodium ion concentration or current. A specific effect of the sucrose on hyperpolarizing currents was observed and noted but not investigated in detail. PMID:14232131

Block of HERG human K(+) channel and IKr of guinea pig cardiomyocytes by chlorpromazine.

PubMed

Lee, So-Young; Choi, Se-Young; Youm, Jae Boum; Ho, Won-Kyung; Earm, Yung E; Lee, Chin O; Jo, Su-Hyun

2004-05-01

Chlorpromazine, a commonly used antipsychotic drug, has been known to induce QT prolongation and torsades de pointes, which can cause sudden death. We studied the effects of chlorpromazine on the human ether-a-go-go-related gene (HERG) channel expressed in Xenopus oocytes and on delayed rectifier K current of guinea pig ventricular myocytes. Application of chlorpromazine showed a dose-dependent decrease in the amplitudes of steady-state currents and tail currents of HERG. The decrease became more pronounced at increasingly positive potential, suggesting that the blockade of HERG by chlorpromazine is voltage dependent. IC50 for chlorpromazine block of HERG current was progressively decreased according to depolarization: IC50 values at -30, 0, and +30 mV were 10.5, 8.8, and 4.9 microM, respectively. The block of HERG current during the voltage step increased with time starting from a level 89% of the control current. In guinea pig ventricular myocytes, bath application of 2 and 5 microM chlorpromazine at 36 degree C blocked rapidly activating delayed rectifier K current (IKr) by 31 and 83%, respectively. How-ever, the same concentrations of chlorpromazine failed to significantly block slowly activating delayed rectifier K current (IKs). Our findings suggest that the arrhythmogenic side effect of chlorpromazine is caused by blockade of HERG and rapid component of delayed rectifier K current rather than by blockade of the slow component.

Soft Computing Approach to Evaluate and Predict Blast-Induced Ground Vibration

NASA Astrophysics Data System (ADS)

Khandelwal, Manoj

2010-05-01

Drilling and blasting is still one of the major economical operations to excavate a rock mass. The consumption of explosive has been increased many folds in recent years. These explosives are mainly used for the exploitation of minerals in mining industry or the removal of undesirable rockmass for community development. The amount of chemical energy converted into mechanical energy to fragment and displace the rockmass is minimal. Only 20 to 30% of this explosive energy is utilized for the actual fragmentation and displacement of rockmass and rest of the energy is wasted in undesirable ill effects, like, ground vibration, air over pressure, fly rock, back break, noise, etc. Ground vibration induced due to blasting is very crucial and critical as compared to other ill effects due to involvement of public residing in the close vicinity of mining sites, regulating and ground vibration standards setting agencies together with mine owners and environmentalists and ecologists. Also, with the emphasis shifting towards eco-friendly, sustainable and geo-environmental activities, the field of ground vibration have now become an important and imperative parameter for safe and smooth running of any mining and civil project. The ground vibration is a wave motion, spreading outward from the blast like ripples spreading outwards due to impact of a stone dropped into a pond of water. As the vibration passes through the surface structures, it induces vibrations in those structures also. Sometimes, due to high ground vibration level, dwellings may get damaged and there is always confrontation between mine management and the people residing in the surroundings of the mine area. There is number of vibration predictors available suggested by different researchers. All the predictors estimate the PPV based on mainly two parameters (maximum charge used per delay and distance between blast face to monitoring point). However, few predictors considered attenuation/damping factor too. For the same excavation site, different predictors give different values of safe PPV vis-à-vis safe charge per delay. There is no uniformity in the predicted result by different predictors. All vibration predictor equations have their site specific constants. Therefore, they cannot be used in a generalized way with confidence and zero level of risk. To overcome on this aspect new soft computing tools like artificial neural network (ANN) has attracted because of its ability to learn from the pattern acquainted before. ANN has the ability to learn from patterns acquainted before. It is a highly interconnected network of a large number of processing elements called neurons in an architecture inspired by the brain. ANN can be massively parallel and hence said to exhibit parallel distributed processing. Once, the network has been trained, with sufficient number of sample data sets, it can make reliable and trustworthy predictions on the basis of its previous learning, about the output related to new input data set of similar pattern. This paper deals the application of ANN for the prediction of ground vibration by taking into consideration of maximum charge per delay and distance between blast face to monitoring point. To investigate the appropriateness of this approach, the predictions by ANN have been also compared with other vibration predictor equations.

Are the current guidelines for surgical delay in hip fractures too rigid? A single center assessment of mortality and economics.

PubMed

Kempenaers, Kristof; Van Calster, Ben; Vandoren, Cindy; Sermon, An; Metsemakers, Willem-Jan; Vanderschot, Paul; Misselyn, Dominique; Nijs, Stefaan; Hoekstra, Harm

2018-06-01

Controversy remains around acceptable surgical delay of acute hip fractures with current guidelines ranging from 24 to 48 h. Increasing healthcare costs force us to consider the economic burden as well. We aimed to evaluate the adjusted effect of surgical delay for hip fracture surgery on early mortality, healthcare costs and readmission rate. We hypothesized that shorter delays resulted in lower early mortality and costs. In this retrospective cohort study 2573 consecutive patients aged ≥50 years were included, who underwent surgery for acute hip fractures between 2009 and 2017. Main endpoints were thirty- and ninety-day mortality, total cost, and readmission rate. Multivariable regression included sex, age and ASA score as covariates. Thirty-day mortality was 5% (n = 133), ninety-day mortality 12% (n = 304). Average total cost was €11960, dominated by hospitalization (59%) and honoraria (23%). Per 24 h delay, the adjusted odds ratio was 1.07 (95% CI 0.98-1.18) for thirty-day mortality, 1.12 (95% CI 1.04-1.19) for ninety-day mortality, and 0.99 (95% CI = 0.88-1.12) for readmission. Per 24 h delay, costs increased with 7% (95% CI 6-8%). For mortality, delay was a weaker predictor than sex, age, and ASA score. For costs, delay was the strongest predictor. We did not find clear cut-points for surgical delay after which mortality or costs increased abruptly. Despite only modest associations with mortality, we observed a steady increase in healthcare costs when delaying surgery. Hence, a more pragmatic approach with surgery as soon as medically and organizationally possible seems justifiable over rigorous implementation of the current guidelines. Copyright © 2018 Elsevier Ltd. All rights reserved.

New Predictive Filters for Compensating the Transport Delay on a Flight Simulator

NASA Technical Reports Server (NTRS)

Guo, Liwen; Cardullo, Frank M.; Houck, Jacob A.; Kelly, Lon C.; Wolters, Thomas E.

2004-01-01

The problems of transport delay in a flight simulator, such as its sources and effects, are reviewed. Then their effects on a pilot-in-the-loop control system are investigated with simulations. Three current prominent delay compensators the lead/lag filter, McFarland filter, and the Sobiski/Cardullo filter were analyzed and compared. This paper introduces two novel delay compensation techniques an adaptive predictor using the Kalman estimator and a state space predictive filter using a reference aerodynamic model. Applications of these two new compensators on recorded data from the NASA Langley Research Center Visual Motion Simulator show that they achieve better compensation over the current ones.

Double-ended metal halide arc discharge lamp with electrically isolated containment shroud

NASA Technical Reports Server (NTRS)

Muzeroll, Martin M. (Inventor)

1994-01-01

A double-ended arc discharge lamp includes a sealed, light-transmissive outer jacket, a light-transmissive shroud mounted within the outer jacket and directly supported by the outer jacket, and an arc discharge tube mounted within the shroud. The arc tube is typically a metal halide arc discharge tube. In a preferred embodiment, the shroud includes an outwardly flared portion at each end. The outwardly flared portions space the shroud from the outer jacket and support the shroud within the outer jacket. The outwardly flared portions of the shroud can be affixed to the outer jacket by fusing. The outer jacket can be provided with inwardly extending dimples for locating the shroud with respect to the outer jacket. In another embodiment, the outer jacket includes reduced diameter portions near each end which are attached to the shroud.

Direct Observation of Zhang-Li Torque Expansion of Magnetic Droplet Solitons

NASA Astrophysics Data System (ADS)

Chung, Sunjae; Le, Q. Tuan; Ahlberg, Martina; Awad, Ahmad A.; Weigand, Markus; Bykova, Iuliia; Khymyn, Roman; Dvornik, Mykola; Mazraati, Hamid; Houshang, Afshin; Jiang, Sheng; Nguyen, T. N. Anh; Goering, Eberhard; Schütz, Gisela; Gräfe, Joachim; Åkerman, Johan

2018-05-01

Magnetic droplets are nontopological dynamical solitons that can be nucleated in nanocontact based spin torque nano-oscillators (STNOs) with perpendicular magnetic anisotropy free layers. While theory predicts that the droplet should be of the same size as the nanocontact, its inherent drift instability has thwarted attempts at observing it directly using microscopy techniques. Here, we demonstrate highly stable magnetic droplets in all-perpendicular STNOs and present the first detailed droplet images using scanning transmission X-ray microscopy. In contrast to theoretical predictions, we find that the droplet diameter is about twice as large as the nanocontact. By extending the original droplet theory to properly account for the lateral current spread underneath the nanocontact, we show that the large discrepancy primarily arises from current-in-plane Zhang-Li torque adding an outward pressure on the droplet perimeter. Electrical measurements on droplets nucleated using a reversed current in the antiparallel state corroborate this picture.

The relationship of outwardly-directed aggression to suicidal ideation and suicide attempts across two high-risk samples

PubMed Central

Swogger, Marc T.; Van Orden, Kimberly A.; Conner, Kenneth R.

2014-01-01

Objective While research has established some relationships between risk factors and specific suicide-related outcomes, in large part the extent to which suicidal ideation and attempts have different risk profiles is unclear. Using two theories of suicidal behavior to guide our hypotheses, we studied the relationship of outwardly-directed aggression to suicidal ideation and attempts in two high-risk samples. Method Participants in study one were 271 criminal offenders in a pretrial diversion program. Participants in study two were 892 psychiatric inpatients who participated in the MacArthur Violence Risk Assessment Study. Results In both studies, after controlling for relevant covariates, outwardly-directed aggression was associated with suicide attempts, but not ideation. Among psychiatric patients, further analyses revealed that outwardly-directed aggression was associated with planned, but not unplanned, suicide attempts. Conclusions That aggression is related to suicide attempts and not ideation is consistent with hypotheses based on both Joiner's (2005) interpersonal theory of suicidal behavior and theories based on a diathesis toward behavioral dysregulation (e.g., Mann, 2009). That aggression was associated with planned suicide attempts is consistent with Joiner's theory. Competing explanations for the results include a potential role of proactive aggression in suicide attempts, particularly planned attempts. PMID:26180654

[The effect of niflumic acid on gamma aminobutyric acid activated current in DRG neurons].

PubMed

Li, Li; Li, Jing; Ma, Ke-Tao; Cheng, Hong-Ju; Zhao, Lei; Wang, Yang; Si, Jun-Qiang

2013-01-01

To explore the modulatory effect of niflumic acid (NFA) on gamma aminobutyric acid (GABA)-activated currents of dorsal root ganglion (DRG) neurons in rat. The whole-cell patch-clamp technique was used to record the NFA- and GABA-activated currents in neurons freshly dissociated from rat DRG neurons. Application of NFA(0.1 - 100 micromol/L) could induce concentration-dependent outward currents in some cells (21/48,43.75%), and GABA (0.1 - 100 micromol/L) could induce concentration-dependent inward currents in some cells(150/159,94.32%). NFA-(100 micromol/L) and GABA-(100 micromol/L) activated currents were (0.27 +/- 0.06) nA (n = 12) and (1.29 +/- 0.72) nA (n = 53) respectively. However, pre-application of NFA (0.1 - 100 micromol/L) could inhibit the GABA-activated inward current which was identified to be GABAA receptor-mediated current. The inhibitory effects of NFA were concentration-dependent. NFA could not alter the EC50 (about 30 micromol/L) and inverse potential (about -10 mV) of GABA-activated current (P > 0.05). Pre-application of NFA exerts a more strong inhibitory effect on the peak value of GABA-activated current.

Rheological behavior of rat mesangial cells during swelling in vitro.

PubMed

Craelius, W; Huang, C J; Guber, H; Palant, C E

1997-01-01

The response of cells to mechanical forces depends on the rheological properties of their membranes and cytoplasm. To characterize those properties, mechanical and electrical responses to swelling were measured in rat mesangial cells (MC) using electrophysiologic and video microscopic techniques. Ion transport rates during hyposmotic exposures were measured with whole-cell recording electrodes. Results showed that cell swelling varied nonlinearly with positive internal pressure, consistent with a viscoelastic cytoplasm. The extrapolated area expansivity modulus for small deformations was estimated to be 450 dyne/cm. Cell swelling, caused either by positive pipet pressure or hyposmotic exposure (40-60 mOsm Kg-1), rapidly induced an outwardly rectifying membrane conductance with an outward magnitude 4-5 times the baseline conductance of 0.9 +/- 0.5 nS (p < .01). Swelling-induced (SI) current was weakly selective for K+ over Na+, partially reversed upon return to isotonicity, and was antagonized by 0.5 mM GdCl3 (p < 0.02; n = 6). Isolated cells treated with GdCl3 rapidly lysed after hypotonic exposure, in contrast to untreated cells that exhibited regulatory volume decrease (RVD). Our results indicate that volume regulation by MC depends upon a large swelling-induced K+ efflux, and suggest that swelling in MC is a viscoelastic process, with a viscosity dependent on the degree of swelling.

The cooperative voltage sensor motion that gates a potassium channel.

PubMed

Pathak, Medha; Kurtz, Lisa; Tombola, Francesco; Isacoff, Ehud

2005-01-01

The four arginine-rich S4 helices of a voltage-gated channel move outward through the membrane in response to depolarization, opening and closing gates to generate a transient ionic current. Coupling of voltage sensing to gating was originally thought to operate with the S4s moving independently from an inward/resting to an outward/activated conformation, so that when all four S4s are activated, the gates are driven to open or closed. However, S4 has also been found to influence the cooperative opening step (Smith-Maxwell et al., 1998a), suggesting a more complex mechanism of coupling. Using fluorescence to monitor structural rearrangements in a Shaker channel mutant, the ILT channel (Ledwell and Aldrich, 1999), that energetically isolates the steps of activation from the cooperative opening step, we find that opening is accompanied by a previously unknown and cooperative movement of S4. This gating motion of S4 appears to be coupled to the internal S6 gate and to two forms of slow inactivation. Our results suggest that S4 plays a direct role in gating. While large transmembrane rearrangements of S4 may be required to unlock the gating machinery, as proposed before, it appears to be the gating motion of S4 that drives the gates to open and close.

The Cooperative Voltage Sensor Motion that Gates a Potassium Channel

PubMed Central

Pathak, Medha; Kurtz, Lisa; Tombola, Francesco; Isacoff, Ehud

2005-01-01

The four arginine-rich S4 helices of a voltage-gated channel move outward through the membrane in response to depolarization, opening and closing gates to generate a transient ionic current. Coupling of voltage sensing to gating was originally thought to operate with the S4s moving independently from an inward/resting to an outward/activated conformation, so that when all four S4s are activated, the gates are driven to open or closed. However, S4 has also been found to influence the cooperative opening step (Smith-Maxwell et al., 1998a), suggesting a more complex mechanism of coupling. Using fluorescence to monitor structural rearrangements in a Shaker channel mutant, the ILT channel (Ledwell and Aldrich, 1999), that energetically isolates the steps of activation from the cooperative opening step, we find that opening is accompanied by a previously unknown and cooperative movement of S4. This gating motion of S4 appears to be coupled to the internal S6 gate and to two forms of slow inactivation. Our results suggest that S4 plays a direct role in gating. While large transmembrane rearrangements of S4 may be required to unlock the gating machinery, as proposed before, it appears to be the gating motion of S4 that drives the gates to open and close. PMID:15623895

Automated delay estimation at signalized intersections : phase I concept and algorithm development.

DOT National Transportation Integrated Search

2011-07-01

Currently there are several methods to measure the performance of surface streets, but their capabilities in dynamically estimating vehicle delay are limited. The objective of this research is to develop a method to automate traffic delay estimation ...

Miniature electrical connector

DOEpatents

Casper, Robert F.

1976-01-01

A miniature coaxial cable electrical connector includes an annular compressible gasket in a receptacle member, the gasket having a generally triangular cross section resiliently engaging and encircling a conically tapered outer surface of a plug member to create an elongated current leakage path at their interface; means for preventing rotation of the plug relative to the receptacle; a metal sleeve forming a portion of the receptacle and encircling the plug member when interconnected; and a split ring in the plug having outwardly and rearwardly projecting fingers spaced from and encircling a portion of a coaxial cable and engageable with the metal sleeve to interlock the receptacle and plug.

Disk Chemistry and Cometary Composition

NASA Astrophysics Data System (ADS)

Markwick, A. J.; Charnley, S. B.

2003-05-01

We will describe current chemical modelling of disks similar to the protosolar nebula. Calculations are being undertaken to determine the spatial and temporal chemistry of the gas and dust within the 5-40AU comet-forming region of the nebula. These theoretical studies aim to determine the contribution of pristine and partially-processed interstellar material from the cool outer nebula, as compared to that obtained from outward radial mixing of matter from the hot inner nebula. Reference Molecular distributions in the inner regions of protostellar disks, Markwick, A. J., Ilgner, M., Millar, T. J., Henning, Th. (2002), Astron. Astrophys., 385, 632.

Disk Chemistry and Cometary Composition

NASA Astrophysics Data System (ADS)

Markwick, A. J.; Charnley, S. B.

2005-01-01

We will describe current chemical modelling of disks similar to the protosolar nebula. Calculations are being undertaken to determine the spatial and temporal chemistry of the gas and dust within the 5-40AU comet-forming region of the nebula. These theoretical studies aim to determine the contribution of pristine and partially-processed interstellar material from the cool outer nebula as compared to that obtained from outward radial mixing of matter from the hot inner nebula. Reference Molecular distributions in the inner regions of protostellar disks Markwick A. J. Ilgner M. Millar T. J. Henning Th. (2002) Astron. Astrophys. 385 632

Dopaminergic lesions of the dorsolateral striatum in rats increase delay discounting in an impulsive choice task.

PubMed

Tedford, Stephanie E; Persons, Amanda L; Napier, T Celeste

2015-01-01

Dysregulated dopamine transmission in striatal circuitry is associated with impulsivity. The current study evaluated the influence of dopaminergic inputs to the dorsolateral striatum on impulsive choice, one aspect of impulsive behavior. We implemented an operant task that measures impulsive choice in rats via delay discounting wherein intracranial self-stimulation (ICSS) was used as the positive reinforcer. To do so, rats were anesthetized to allow implanting of a stimulating electrode within the lateral hypothalamus of one hemisphere and bilateral dorsal striatal injections of the dopaminergic toxin, 6-OHDA (lesioned) or its vehicle (sham). Following recovery, rats were trained in a delay discounting task wherein they selected between a small ICSS current presented immediately after lever pressing, and a large ICSS current presented following a 0 to 15 s delay upon pressing the alternate lever. Task acquisition and reinforcer discrimination were similar for lesioned and sham rats. All rats exhibited an initial preference for the large reinforcer, and as the delay was increased, preference for the large reinforcer was decreased indicating that the subjective value of the large reinforcer was discounted as a function of delay time. However, this discounting effect was significantly enhanced in lesioned rats for the longer delays. These data reveal a contribution of dopaminergic inputs to the dorsolateral striatum on impulsive choice behavior, and provide new insights into neural substrates underlying discounting behaviors.

Dopaminergic Lesions of the Dorsolateral Striatum in Rats Increase Delay Discounting in an Impulsive Choice Task

PubMed Central

Tedford, Stephanie E.; Persons, Amanda L.; Napier, T. Celeste

2015-01-01

Dysregulated dopamine transmission in striatal circuitry is associated with impulsivity. The current study evaluated the influence of dopaminergic inputs to the dorsolateral striatum on impulsive choice, one aspect of impulsive behavior. We implemented an operant task that measures impulsive choice in rats via delay discounting wherein intracranial self-stimulation (ICSS) was used as the positive reinforcer. To do so, rats were anesthetized to allow implanting of a stimulating electrode within the lateral hypothalamus of one hemisphere and bilateral dorsal striatal injections of the dopaminergic toxin, 6-OHDA (lesioned) or its vehicle (sham). Following recovery, rats were trained in a delay discounting task wherein they selected between a small ICSS current presented immediately after lever pressing, and a large ICSS current presented following a 0 to 15s delay upon pressing the alternate lever. Task acquisition and reinforcer discrimination were similar for lesioned and sham rats. All rats exhibited an initial preference for the large reinforcer, and as the delay was increased, preference for the large reinforcer was decreased indicating that the subjective value of the large reinforcer was discounted as a function of delay time. However, this discounting effect was significantly enhanced in lesioned rats for the longer delays. These data reveal a contribution of dopaminergic inputs to the dorsolateral striatum on impulsive choice behavior, and provide new insights into neural substrates underlying discounting behaviors. PMID:25927685

An efficient current-based logic cell model for crosstalk delay analysis

NASA Astrophysics Data System (ADS)

Nazarian, Shahin; Das, Debasish

2013-04-01

Logic cell modelling is an important component in the analysis and design of CMOS integrated circuits, mostly due to nonlinear behaviour of CMOS cells with respect to the voltage signal at their input and output pins. A current-based model for CMOS logic cells is presented, which can be used for effective crosstalk noise and delta delay analysis in CMOS VLSI circuits. Existing current source models are expensive and need a new set of Spice-based characterisation, which is not compatible with typical EDA tools. In this article we present Imodel, a simple nonlinear logic cell model that can be derived from the typical cell libraries such as NLDM, with accuracy much higher than NLDM-based cell delay models. In fact, our experiments show an average error of 3% compared to Spice. This level of accuracy comes with a maximum runtime penalty of 19% compared to NLDM-based cell delay models on medium-sized industrial designs.

Coronary artery wall imaging.

PubMed

Keegan, Jennifer

2015-05-01

Like X-Ray contrast angiography, MR coronary angiograms show the vessel lumens rather than the vessels themselves. Consequently, outward remodeling of the vessel wall, which occurs in subclinical coronary disease before luminal narrowing, cannot be seen. The current gold standard for assessing the coronary vessel wall is intravascular ultrasound, and more recently, optical coherence tomography, both of which are invasive and use ionizing radiation. A noninvasive, low-risk technique for assessing the vessel wall would be beneficial to cardiologists interested in the early detection of preclinical disease and for the safe monitoring of the progression or regression of disease in longitudinal studies. In this review article, the current state of the art in MR coronary vessel wall imaging is discussed, together with validation studies and recent developments. © 2014 Wiley Periodicals, Inc.

Peculiarities of Spacecraft Photoelectron Shield Formation in Magnetic Field

NASA Astrophysics Data System (ADS)

Veselov, Mikhail; Chugunin, Dmitriy

Traditionally, the current balance equations for a spacecraft in space plasma rely on the electric field of positively charged spacecraft. Equilibrium potential V is derived from currents outward and toward the spacecraft body. The currents are in turn functions of V. However, in reality photoelectrons move in both the electric field of the spacecraft and the Earth or the interplanetary magnetic field. This causes an anisotropic distribution of photoelectrons along a magnetic field line with the characteristic size of the order of several photoelectron gyro-radii. As a result, confinement of photoelectrons in the spacecraft-related electric field is much longer. Thus, a fraction of returned photoelectrons in the electron current toward the spacecraft can be rather great and may even dominate several times over the ambient electrons’ fraction. Modeled ph-electron trajectories as well as general photoelectron shield distribution around spacecraft are represented, and comparison of experimental data on the electron density with the magnetic flux tube model is discussed.

Reversibility of electrophysiological changes induced by chronic high-altitude hypoxia in adult rat heart.

PubMed

Chouabe, C; Amsellem, J; Espinosa, L; Ribaux, P; Blaineau, S; Mégas, P; Bonvallet, R

2002-04-01

Recent studies indicate that regression of left ventricular hypertrophy normalizes membrane ionic current abnormalities. This work was designed to determine whether regression of right ventricular hypertrophy induced by permanent high-altitude exposure (4,500 m, 20 days) in adult rats also normalizes changes of ventricular myocyte electrophysiology. According to the current data, prolonged action potential, decreased transient outward current density, and increased inward sodium/calcium exchange current density normalized 20 days after the end of altitude exposure, whereas right ventricular hypertrophy evidenced by both the right ventricular weight-to-heart weight ratio and the right ventricular free wall thickness measurement normalized 40 days after the end of altitude exposure. This morphological normalization occurred at both the level of muscular tissue, as shown by the decrease toward control values of some myocyte parameters (perimeter, capacitance, and width), and the level of the interstitial collagenous connective tissue. In the chronic high-altitude hypoxia model, the regression of right ventricular hypertrophy would not be a prerequisite for normalization of ventricular electrophysiological abnormalities.

A TREND BETWEEN COLD DEBRIS DISK TEMPERATURE AND STELLAR TYPE: IMPLICATIONS FOR THE FORMATION AND EVOLUTION OF WIDE-ORBIT PLANETS

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

Ballering, Nicholas P.; Rieke, George H.; Su, Kate Y. L.

2013-09-20

Cold debris disks trace the limits of planet formation or migration in the outer regions of planetary systems, and thus have the potential to answer many of the outstanding questions in wide-orbit planet formation and evolution. We characterized the infrared excess spectral energy distributions of 174 cold debris disks around 546 main-sequence stars observed by both the Spitzer Infrared Spectrograph and the Multiband Imaging Photometer for Spitzer. We found a trend between the temperature of the inner edges of cold debris disks and the stellar type of the stars they orbit. This argues against the importance of strictly temperature-dependent processesmore » (e.g., non-water ice lines) in setting the dimensions of cold debris disks. Also, we found no evidence that delayed stirring causes the trend. The trend may result from outward planet migration that traces the extent of the primordial protoplanetary disk, or it may result from planet formation that halts at an orbital radius limited by the efficiency of core accretion.« less

N-Acetylcysteine-induced vasodilatation is modulated by KATP channels, Na+/K+-ATPase activity and intracellular calcium concentration: An in vitro study.

PubMed

Vezir, Özden; Çömelekoğlu, Ülkü; Sucu, Nehir; Yalın, Ali Erdinç; Yılmaz, Şakir Necat; Yalın, Serap; Söğüt, Fatma; Yaman, Selma; Kibar, Kezban; Akkapulu, Merih; Koç, Meryem İlkay; Seçer, Didem

2017-08-01

In this study, we aimed to investigate the role of ATP-sensitive potassium (K ATP ) channel, Na + /K + -ATPase activity, and intracellular calcium levels on the vasodilatory effect of N-acetylcysteine (NAC) in thoracic aorta by using electrophysiological and molecular techniques. Rat thoracic aorta ring preparations and cultured thoracic aorta cells were divided into four groups as control, 2mM NAC, 5mM NAC, and 10mM NAC. Thoracic aorta rings were isolated from rats for measurements of relaxation responses and Na + /K + -ATPase activity. In the cultured thoracic aorta cells, we measured the currents of K ATP channel, the concentration of intracellular calcium and mRNA expression level of K ATP channel subunits (KCNJ8, KCNJ11, ABCC8 and ABCC9). The relaxation rate significantly increased in all NAC groups compared to control. Similarly, Na + /K + - ATPase activity also significantly decreased in NAC groups. Outward K ATP channel current significantly increased in all NAC groups compared to the control group. Intracellular calcium concentration decreased significantly in all groups with compared control. mRNA expression level of ABCC8 subunit significantly increased in all NAC groups compared to the control group. Pearson correlation analysis showed that relaxation rate was significantly associated with K ATP current, intracellular calcium concentration, Na + /K + -ATPase activity and mRNA expression level of ABCC8 subunit. Our findings suggest that NAC relaxes vascular smooth muscle cells through a direct effect on K ATP channels, by increasing outward K+ flux, partly by increasing mRNA expression of K ATP subunit ABCC8, by decreasing in intracellular calcium and by decreasing in Na + /K + -ATPase activity. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

KChIP2 genotype dependence of transient outward current (Ito) properties in cardiomyocytes isolated from male and female mice

PubMed Central

Waldschmidt, Lara; Junkereit, Vera; Bähring, Robert

2017-01-01

The transient outward current (Ito) in cardiomyocytes is largely mediated by Kv4 channels associated with Kv Channel Interacting Protein 2 (KChIP2). A knockout model has documented the critical role of KChIP2 in Ito expression. The present study was conducted to characterize in both sexes the dependence of Ito properties, including current magnitude, inactivation kinetics, recovery from inactivation and voltage dependence of inactivation, on the number of functional KChIP2 alleles. For this purpose we performed whole-cell patch-clamp experiments on isolated left ventricular cardiomyocytes from male and female mice which had different KChIP2 genotypes; i.e., wild-type (KChIP2+/+), heterozygous knockout (KChIP2+/-) or complete knockout of KChIP2 (KChIP2-/-). We found in both sexes a KChIP2 gene dosage effect (i.e., a proportionality between number of alleles and phenotype) on Ito magnitude, however, concerning other Ito properties, KChIP2+/- resembled KChIP2+/+. Only in the total absence of KChIP2 (KChIP2-/-) we observed a slowing of Ito kinetics, a slowing of recovery from inactivation and a negative shift of a portion of the voltage dependence of inactivation. In a minor fraction of KChIP2-/- myocytes Ito was completely lost. The distinct KChIP2 genotype dependences of Ito magnitude and inactivation kinetics, respectively, seen in cardiomyocytes were reproduced with two-electrode voltage-clamp experiments on Xenopus oocytes expressing Kv4.2 and different amounts of KChIP2. Our results corroborate the critical role of KChIP2 in controlling Ito properties. They demonstrate that the Kv4.2/KChIP2 interaction in cardiomyocytes is highly dynamic, with a clear KChIP2 gene dosage effect on Kv4 channel surface expression but not on inactivation gating. PMID:28141821

KChIP2 genotype dependence of transient outward current (Ito) properties in cardiomyocytes isolated from male and female mice.

PubMed

Waldschmidt, Lara; Junkereit, Vera; Bähring, Robert

2017-01-01

The transient outward current (Ito) in cardiomyocytes is largely mediated by Kv4 channels associated with Kv Channel Interacting Protein 2 (KChIP2). A knockout model has documented the critical role of KChIP2 in Ito expression. The present study was conducted to characterize in both sexes the dependence of Ito properties, including current magnitude, inactivation kinetics, recovery from inactivation and voltage dependence of inactivation, on the number of functional KChIP2 alleles. For this purpose we performed whole-cell patch-clamp experiments on isolated left ventricular cardiomyocytes from male and female mice which had different KChIP2 genotypes; i.e., wild-type (KChIP2+/+), heterozygous knockout (KChIP2+/-) or complete knockout of KChIP2 (KChIP2-/-). We found in both sexes a KChIP2 gene dosage effect (i.e., a proportionality between number of alleles and phenotype) on Ito magnitude, however, concerning other Ito properties, KChIP2+/- resembled KChIP2+/+. Only in the total absence of KChIP2 (KChIP2-/-) we observed a slowing of Ito kinetics, a slowing of recovery from inactivation and a negative shift of a portion of the voltage dependence of inactivation. In a minor fraction of KChIP2-/- myocytes Ito was completely lost. The distinct KChIP2 genotype dependences of Ito magnitude and inactivation kinetics, respectively, seen in cardiomyocytes were reproduced with two-electrode voltage-clamp experiments on Xenopus oocytes expressing Kv4.2 and different amounts of KChIP2. Our results corroborate the critical role of KChIP2 in controlling Ito properties. They demonstrate that the Kv4.2/KChIP2 interaction in cardiomyocytes is highly dynamic, with a clear KChIP2 gene dosage effect on Kv4 channel surface expression but not on inactivation gating.

Transient Outward K+ Current (Ito) Underlies the Right Ventricular Initiation of Polymorphic Ventricular Tachycardia in a Transgenic Rabbit Model of Long-QT Syndrome Type 1.

PubMed

Choi, Bum-Rak; Li, Weiyan; Terentyev, Dmitry; Kabakov, Anatoli Y; Zhong, Mingwang; Rees, Colin M; Terentyeva, Radmila; Kim, Tae Yun; Qu, Zhilin; Peng, Xuwen; Karma, Alain; Koren, Gideon

2018-06-01

Sudden death in long-QT syndrome type 1 (LQT1), an inherited disease caused by loss-of-function mutations in KCNQ1, is triggered by early afterdepolarizations (EADs) that initiate polymorphic ventricular tachycardia (pVT). We investigated ionic mechanisms that underlie pVT in LQT1 using a transgenic rabbit model of LQT1. Optical mapping, cellular patch clamping, and computer modeling were used to elucidate the mechanisms of EADs in transgenic LQT1 rabbits. The results showed that shorter action potential duration in the right ventricle (RV) was associated with focal activity during pVT initiation. RV cardiomyocytes demonstrated higher incidence of EADs under 50 nmol/L isoproterenol. Voltage-clamp studies revealed that the transient outward potassium current (I to ) magnitude was 28% greater in RV associated with KChiP2 but with no differences in terms of calcium-cycling kinetics and other sarcolemmal currents. Perfusing with the I to blocker 4-aminopyridine changed the initial focal sites of pVT from the RV to the left ventricle, corroborating the role of I to in pVT initiation. Computer modeling showed that EADs occur preferentially in the RV because of the larger conductance of the slow-inactivating component of I to , which repolarizes the membrane potential sufficiently rapidly to allow reactivation of I Ca,L before I Kr has had sufficient time to activate. I to heterogeneity creates both triggers and an arrhythmogenic substrate in LQT1. In the absence of I Ks , I to interactions with I Ca,L and I Kr promote EADs in the RV while prolonging action potential duration in the left ventricle. This heterogeneity of action potential enhances dispersion of refractoriness and facilitates conduction blocks that initiate pVTs. © 2018 American Heart Association, Inc.

Delay of gratification by orangutans (Pongo pygmaeus) in the accumulation task.

PubMed

Parrish, Audrey E; Perdue, Bonnie M; Stromberg, Erin E; Bania, Amanda E; Evans, Theodore A; Beran, Michael J

2014-05-01

There is considerable evidence indicating that chimpanzees can delay gratification for extended time intervals, particularly in the accumulation task in which food items accumulate within a participant's reach until the participant begins to consume them. However, there is limited evidence that other ape species might also exhibit this capacity, despite there being a number of similar studies indicating that nonape species (e.g., monkeys and birds) can delay gratification, but not for nearly as long as chimpanzees. To help define the taxonomic distribution of delay of gratification behavior in the order Primates, we tested 6 orangutans in the current experiments and compared their performance with comparable data from a previous study with capuchin monkeys. We varied delay length and visibility of the items that were still available for accumulation to determine the impact of these factors on performance. Species differences on the accumulation task emerged when comparing the current data to data from a previous study. Orangutans outperformed capuchin monkeys, suggesting that ape species may generally show better delay of gratification and delay maintenance abilities than monkeys. However, more studies are necessary to rule out alternative hypotheses on the distribution of delay maintenance abilities across primate species. ©2014 APA, all rights reserved.

Structure and molecular mechanism of a nucleobase-cation-symport-1 family transporter.

PubMed

Weyand, Simone; Shimamura, Tatsuro; Yajima, Shunsuke; Suzuki, Shun'ichi; Mirza, Osman; Krusong, Kuakarun; Carpenter, Elisabeth P; Rutherford, Nicholas G; Hadden, Jonathan M; O'Reilly, John; Ma, Pikyee; Saidijam, Massoud; Patching, Simon G; Hope, Ryan J; Norbertczak, Halina T; Roach, Peter C J; Iwata, So; Henderson, Peter J F; Cameron, Alexander D

2008-10-31

The nucleobase-cation-symport-1 (NCS1) transporters are essential components of salvage pathways for nucleobases and related metabolites. Here, we report the 2.85-angstrom resolution structure of the NCS1 benzyl-hydantoin transporter, Mhp1, from Microbacterium liquefaciens. Mhp1 contains 12 transmembrane helices, 10 of which are arranged in two inverted repeats of five helices. The structures of the outward-facing open and substrate-bound occluded conformations were solved, showing how the outward-facing cavity closes upon binding of substrate. Comparisons with the leucine transporter LeuT(Aa) and the galactose transporter vSGLT reveal that the outward- and inward-facing cavities are symmetrically arranged on opposite sides of the membrane. The reciprocal opening and closing of these cavities is synchronized by the inverted repeat helices 3 and 8, providing the structural basis of the alternating access model for membrane transport.

Process for slip casting textured tubular structures

DOEpatents

Steinlage, Greg A.; Trumble, Kevin P.; Bowman, Keith J.

2002-01-01

A process for centrifugal slip casting a textured hollow tube. A slip made up of a carrier fluid and a suspended powder is introduced into a porous mold which is rotated at a speed sufficient to create a centrifugal force that forces the slip radially outward toward the inner surface of the mold. The suspended powder, which is formed of particles having large dimensional aspect ratios such as particles of superconductive BSCCO, settles in a textured fashion radially outward toward the mold surface. The carrier fluid of the slip passes by capillary action radially outward around the settled particles and into the absorbent mold. A layer of mold release material is preferably centrifugally slip cast to cover the mold inner surface prior to the introduction of the BSCCO slip, and the mold release layer facilitates removal of the BSCCO greenbody from the mold without fracturing.

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

Lee, Ching-Pang; Tham, Kok-Mun; Schroeder, Eric

An outer rim seal arrangement (10), including: an annular rim (70) centered about a longitudinal axis (30) of a rotor disc (31), extending fore and having a fore-end (72), an outward-facing surface (74), and an inward-facing surface (76); a lower angel wing (62) extending aft from a base of a turbine blade (22) and having an aft end (64) disposed radially inward of the rim inward-facing surface to define a lower angel wing seal gap (80); an upper angel wing (66) extending aft from the turbine blade base and having an aft end (68) disposed radially outward of the rimmore » outward-facing surface to define a upper angel wing seal gap (80, 82); and guide vanes (100) disposed on the rim inward-facing surface in the lower angel wing seal gap. Pumping fins (102) may be disposed on the upper angel wing seal aft end in the upper angel wing seal gap.« less

Housing and Neighborhood Characteristics and Latino Farmworker Family Well-Being

PubMed Central

Arcury, Thomas A.; Trejo, Grisel; Suerken, Cynthia K.; Grzywacz, Joseph G.; Ip, Edward H.; Quandt, Sara A.

2014-01-01

Housing quality and neighborhood characteristics affect individual health and family well-being. This analysis describes characteristics of farmworker housing and neighborhoods and delineates the associations of housing and local neighborhood with indicators of family well-being. Mothers in North Carolina farmworker families (n=248) completed interviews in 2011-2012. Family well-being measures included stress, family conflict, and outward orientation. Housing measures included ownership and facilities, and neighborhood measures included heavy traffic and driving time to grocery stores. Families experienced elevated stress and conflict, and limited outward orientation. Few owned their homes, which were generally crowded. Few had enclosed play spaces for their children. For many, traffic made it difficult to walk on the street. Housing and neighborhood characteristics were related to increased stress and limited outward orientation. Housing and neighborhood characteristics are important for research on the health of families in vulnerable populations, such as farmworker families. PMID:25367531

Factors influencing patient compliance with therapeutic regimens in chronic heart failure: A critical incident technique analysis.

PubMed

Strömberg, A; Broström, A; Dahlström, U; Fridlund, B

1999-01-01

The aim of this study was to identify factors influencing compliance with prescribed treatment in patients with chronic heart failure. A qualitative design with a critical incident technique was used. Incidents were collected through interviews with 25 patients with heart failure strategically selected from a primary health care clinic, a medical ward, and a specialist clinic. Two hundred sixty critical incidents were identified in the interviews and 2 main areas emerged in the analysis: inward factors and outward factors. The inward factors described how compliance was influenced by the personality of the patient, the disease, and the treatment. The outward factors described how compliance was influenced by social activities, social relationships, and health care professionals. By identifying the inward and outward factors influencing patients with chronic heart failure, health care professionals can assess whether intervention is needed to increase compliance.

Housing and Neighborhood Characteristics and Latino Farmworker Family Well-Being.

PubMed

Arcury, Thomas A; Trejo, Grisel; Suerken, Cynthia K; Grzywacz, Joseph G; Ip, Edward H; Quandt, Sara A

2015-10-01

Housing quality and neighborhood characteristics affect individual health and family well-being. This analysis describes characteristics of farmworker housing and neighborhoods and delineates the associations of housing and local neighborhood with indicators of family well-being. Mothers in North Carolina farmworker families (n = 248) completed interviews in 2011-2012. Family well-being measures included stress, family conflict, and outward orientation. Housing measures included ownership and facilities, and neighborhood measures included heavy traffic and driving time to grocery stores. Families experienced elevated stress and conflict, and limited outward orientation. Few owned their homes, which were generally crowded. Few had enclosed play spaces for their children. For many, traffic made it difficult to walk on the street. Housing and neighborhood characteristics were related to increased stress and limited outward orientation. Housing and neighborhood characteristics are important for research on the health of families in vulnerable populations, such as farmworker families.

Observations of simultaneous coronal loop shrinkage and expansion during the decay phase of a solar flare

NASA Astrophysics Data System (ADS)

Khan, J. I.; Fletcher, L.; Nitta, N. V.

2006-07-01

We report what we believe are the first direct and unambiguous observations of simultaneous coronal magnetic flux loop shrinkage and expansion during the decay phase of a solar flare. The retracting and expanding loops were observed nearly face-on (i.e., with the loop major axis approximately orthogonal to the line of sight) in emission in imaging data from the Yohkoh Soft X-ray Telescope (SXT). The retracting loop is observed to shrink with a speed of 118 ± 66 km s-1. The faint outward moving loop-like feature occurred ~200´´ above the shrinking loop during the time of the shrinking loop. We estimate the speed of the outward moving loop was ~129 ± 74 km s-1. We interpret the shrinking loop and simultaneous outward moving loop as direct evidence for reconnected magnetic field lines during a flare.

The Air Blast Wave from a Nuclear Explosion

NASA Astrophysics Data System (ADS)

Reines, Frederick

The sudden, large scale release of energy in the explosion of a nuclear bomb in air gives rise, in addition to nuclear emanations such as neutrons and gamma rays, to an extremely hot, rapidly expanding mass of air.** The rapidly expanding air mass has an initial temperature in the vicinity of a few hundred thousand degrees and for this reason it glows in its early stages with an intensity of many suns. It is important that the energy density in this initial "ball of fire" is of the order of 3 × 103 times that found in a detonating piece of TNT and hence that the initial stages of the large scale air motion produced by a nuclear explosion has no counterpart in an ordinary. H. E. explosion. Further, the relatively low temperatures ˜2,000°C associated with the initial stages of an H. E. detonation implies that the thermal radiation which it emits is a relatively insignificant fraction of the total energy involves. This point is made more striking when it is remembered that the thermal energy emitted by a hot object varies directly with the temperature in the Rayleigh Jeans region appropriate to the present discussion. The expansion of the air mass heated by the nuclear reaction produces, in qualitatively the same manner as in an H.E. explosion or the bursting of a high pressure balloon, an intense sharp pressure pulse, a shock wave, in the atmosphere. As the pressure pulse spreads outward it weakens due to the combined effects of divergence and the thermodynamically irreversible nature of the shock wave. The air comprising such a pressure pulse or blast wave moves first radially outward and then back towards the center as the blast wave passes. Since a permanent outward displacement of an infinite mass of air would require unlimited energy, the net outward displacement of the air distant from an explosion must approach zero with increasing distance. As the distance from the explosion is diminished the net outward displacement due to irreversible shock heating of the air increases and in the limit of small distances and increasingly strong shocks the net outward displacement of the shocked air is equal to the maximum outward displacement. These statements are applicable for short times of the order of seconds following the explosion since the heated air l behind by the shock wave will rise. The pressures and air mass motions associated with the rise of the atomic cloud are relatively unimportant in the free air pressure ranges from 2-15 psi for bomb yields under 100 kilotons (KT)…

Molecular Basis of Cardiac Delayed Rectifier Potassium Channel Function and Pharmacology.

PubMed

Wu, Wei; Sanguinetti, Michael C

2016-06-01

Human cardiomyocytes express 3 distinct types of delayed rectifier potassium channels. Human ether-a-go-go-related gene (hERG) channels conduct the rapidly activating current IKr; KCNQ1/KCNE1 channels conduct the slowly activating current IKs; and Kv1.5 channels conduct an ultrarapid activating current IKur. Here the authors provide a general overview of the mechanistic and structural basis of ion selectivity, gating, and pharmacology of the 3 types of cardiac delayed rectifier potassium ion channels. Most blockers bind to S6 residues that line the central cavity of the channel, whereas activators interact with the channel at 4 symmetric binding sites outside the cavity. Copyright © 2016 Elsevier Inc. All rights reserved.

Interaction of a dinoflagellate neurotoxin with voltage-activated ion channels in a marine diatom.

PubMed

Kitchen, Sheila A; Bourdelais, Andrea J; Taylor, Alison R

2018-01-01

The potent neurotoxins produced by the harmful algal bloom species Karenia brevis are activators of sodium voltage-gated channels (VGC) in animals, resulting in altered channel kinetics and membrane hyperexcitability. Recent biophysical and genomic evidence supports widespread presence of homologous sodium (Na + ) and calcium (Ca 2+ ) permeable VGCs in unicellular algae, including marine phytoplankton. We therefore hypothesized that VGCs of these phytoplankton may be an allelopathic target for waterborne neurotoxins produced by K. brevis blooms that could lead to ion channel dysfunction and disruption of signaling in a similar manner to animal Na + VGCs. We examined the interaction of brevetoxin-3 (PbTx-3), a K. brevis neurotoxin, with the Na + /Ca 2+ VGC of the non-toxic diatom Odontella sinensi s using electrophysiology. Single electrode current- and voltage- clamp recordings from O. sinensis in the presence of PbTx-3 were used to examine the toxin's effect on voltage gated Na + /Ca 2+ currents. In silico analysis was used to identify the putative PbTx binding site in the diatoms. We identified Na + /Ca 2+ VCG homologs from the transcriptomes and genomes of 12 diatoms, including three transcripts from O. sinensis and aligned them with site-5 of Na + VGCs, previously identified as the PbTx binding site in animals. Up to 1 µM PbTx had no effect on diatom resting membrane potential or membrane excitability. The kinetics of fast inward Na + /Ca 2+ currents that underlie diatom action potentials were also unaffected. However, the peak inward current was inhibited by 33%, delayed outward current was inhibited by 25%, and reversal potential of the currents shifted positive, indicating a change in permeability of the underlying channels. Sequence analysis showed a lack of conservation of the PbTx binding site in diatom VGC homologs, many of which share molecular features more similar to single-domain bacterial Na + /Ca 2+ VGCs than the 4-domain eukaryote channels. Although membrane excitability and the kinetics of action potential currents were unaffected, the permeation of the channels underlying the diatom action potential was significantly altered in the presence of PbTx-3. However, at environmentally relevant concentrations the effects of PbTx- on diatom voltage activated currents and interference of cell signaling through this pathway may be limited. The relative insensitivity of phytoplankton VGCs may be due to divergence of site-5 (the putative PbTx binding site), and in some cases, such as O. sinensis , resistance to toxin effects may be because of evolutionary loss of the 4-domain eukaryote channel, while retaining a single domain bacterial-like VGC that can substitute in the generation of fast action potentials.

Dual control of cardiac Na+–Ca2+ exchange by PIP2: electrophysiological analysis of direct and indirect mechanisms

PubMed Central

Yaradanakul, Alp; Feng, Siyi; Shen, Chengcheng; Lariccia, Vincenzo; Lin, Mei-Jung; Yang, Jinsong; Kang, T M; Dong, Ping; Yin, Helen L; Albanesi, Joseph P; Hilgemann, Donald W

2007-01-01

Cardiac Na+–Ca2+ exchange (NCX1) inactivates in excised membrane patches when cytoplasmic Ca2+ is removed or cytoplasmic Na+ is increased. Exogenous phosphatidylinositol-4,5-bis-phosphate (PIP2) can ablate both inactivation mechanisms, while it has no effect on inward exchange current in the absence of cytoplasmic Na+. To probe PIP2 effects in intact cells, we manipulated PIP2 metabolism by several means. First, we used cell lines with M1 (muscarinic) receptors that couple to phospholipase C's (PLCs). As expected, outward NCX1 current (i.e. Ca2+ influx) can be strongly inhibited when M1 agonists induce PIP2 depletion. However, inward currents (i.e. Ca2+ extrusion) without cytoplasmic Na+ can be increased markedly in parallel with an increase of cell capacitance (i.e. membrane area). Similar effects are incurred by cytoplasmic perfusion of GTPγS or the actin cytoskeleton disruptor latrunculin, even in the presence of non-hydrolysable ATP (AMP-PNP). Thus, G-protein signalling may increase NCX1 currents by destabilizing membrane cytoskeleton–PIP2 interactions. Second, to increase PIP2 we directly perfused PIP2 into cells. Outward NCX1 currents increase as expected. But over minutes currents decline substantially, and cell capacitance usually decreases in parallel. Third, using BHK cells with stable NCX1 expression, we increased PIP2 by transient expression of a phosphatidylinositol-4-phosphate-5-kinase (hPIP5KIβ) and a PI4-kinase (PI4KIIα). NCX1 current densities were decreased by > 80 and 40%, respectively. Fourth, we generated transgenic mice with 10-fold cardiac-specific overexpression of PI4KIIα. This wortmannin-insensitive PI4KIIα was chosen because basal cardiac phosphoinositides are nearly insensitive to wortmannin, and surface membrane PI4-kinase activity, defined functionally in excised patches, is not blocked by wortmannin. Both phosphatidylinositol-4-phosphate (PIP) and PIP2 were increased significantly, while NCX1 current densities were decreased by 78% with no loss of NCX1 expression. Most mice developed cardiac hypertrophy, and immunohistochemical analysis suggests that NCX1 is redistributed away from the outer sarcolemma. Cholera toxin uptake was increased 3-fold, suggesting that clathrin-independent endocytosis is enhanced. We conclude that direct effects of PIP2 to activate NCX1 can be strongly modulated by opposing mechanisms in intact cells that probably involve membrane cytoskeleton remodelling and membrane trafficking. PMID:17540705

Effect of trimetazidine treatment on the transient outward potassium current of the left ventricular myocytes of rats with streptozotocin-induced type 1 diabetes mellitus.

PubMed

Xiang, Yu-luan; He, Li; Xiao, Jun; Xia, Shuang; Deng, Song-bai; Xiu, Yun; She, Qiang

2012-03-01

Cardiovascular complications are a leading cause of mortality in patients with diabetes mellitus (DM). The present study was designed to investigate the effects of trimetazidine (TMZ), an anti-angina drug, on transient outward potassium current (Ito) remodeling in ventricular myocytes and the plasma contents of free fatty acid (FFA) and glucose in DM. Sprague-Dawley rats, 8 weeks old and weighing 200-250 g, were randomly divided into three groups of 20 animals each. The control group was injected with vehicle (1 mM citrate buffer), the DM group was injected with 65 mg/kg streptozotocin (STZ) for induction of type 1 DM, and the DM + TMZ group was injected with the same dose of STZ followed by a 4-week treatment with TMZ (60 mg·kg-1·day-1). All animals were then euthanized and their hearts excised and subjected to electrophysiological measurements or gene expression analyses. TMZ exposure significantly reversed the increased plasma FFA level in diabetic rats, but failed to change the plasma glucose level. The amplitude of Ito was significantly decreased in left ventricular myocytes from diabetic rats relative to control animals (6.25 ± 1.45 vs 20.72 ± 2.93 pA/pF at +40 mV). The DM-associated Ito reduction was attenuated by TMZ. Moreover, TMZ treatment reversed the increased expression of the channel-forming alpha subunit Kv1.4 and the decreased expression of Kv4.2 and Kv4.3 in diabetic rat hearts. These data demonstrate that TMZ can normalize, or partially normalize, the increased plasma FFA content, the reduced Ito of ventricular myocytes, and the altered expression Kv1.4, Kv4.2, and Kv4.3 in type 1 DM.

Wintertime dynamics in the coastal northeastern Adriatic Sea: the NAdEx 2015 experiment

NASA Astrophysics Data System (ADS)

Vilibić, Ivica; Mihanović, Hrvoje; Janeković, Ivica; Denamiel, Cléa; Poulain, Pierre-Marie; Orlić, Mirko; Dunić, Natalija; Dadić, Vlado; Pasarić, Mira; Muslim, Stipe; Gerin, Riccardo; Matić, Frano; Šepić, Jadranka; Mauri, Elena; Kokkini, Zoi; Tudor, Martina; Kovač, Žarko; Džoić, Tomislav

2018-03-01

The paper investigates the wintertime dynamics of the coastal northeastern Adriatic Sea and is based on numerical modelling and in situ data collected through field campaigns executed during the winter and spring of 2015. The data were collected with a variety of instruments and platforms (acoustic Doppler current profilers, conductivity-temperature-depth probes, glider, profiling float) and are accompanied by the atmosphere-ocean ALADIN/ROMS modelling system. The research focused on the dense-water formation (DWF), thermal changes, circulation, and water exchange between the coastal and open Adriatic. According to both observations and modelling results, dense waters are formed in the northeastern coastal Adriatic during cold bora outbreaks. However, the dense water formed in this coastal region has lower densities than the dense water formed in the open Adriatic due to lower salinities. Since the coastal area is deeper than the open Adriatic, the observations indicate (i) balanced inward-outward exchange at the deep connecting channels of denser waters coming from the open Adriatic DWF site and less-dense waters coming from the coastal region and (ii) outward flow of less-dense waters dominating in the intermediate and surface layers. The latter phenomenon was confirmed by the model, even if it significantly underestimates the currents and transports in the connecting channels. The median residence time of the coastal area is estimated to be approximately 20 days, indicating that the coastal area may be renewed relatively quickly by the open Adriatic waters. The data that were obtained represent a comprehensive marine dataset that can be used to calibrate atmospheric and oceanic numerical models and point to several interesting phenomena to be investigated in the future.

Expression and high glucose-mediated regulation of K+ channel interacting protein 3 (KChIP3) and KV4 channels in retinal Müller glial cells.

PubMed

Chavira-Suárez, Erika; Sandoval, Alejandro; Felix, Ricardo; Lamas, Mónica

2011-01-14

Normal vision depends on the correct function of retinal neurons and glia and it is impaired in the course of diabetic retinopathy. Müller cells, the main glial cells of the retina, suffer morphological and functional alterations during diabetes participating in the pathological retinal dysfunction. Recently, we showed that Müller cells express the pleiotropic protein potassium channel interacting protein 3 (KChIP3), an integral component of the voltage-gated K(+) channels K(V)4. Here, we sought to analyze the role of KChIP3 in the molecular mechanisms underlying hyperglycemia-induced phenotypic changes in the glial elements of the retina. The expression and function of KChIp3 was analyzed in vitro in rat Müller primary cultures grown under control (5.6 mM) or high glucose (25 mM) (diabetic-like) conditions. We show the up-regulation of KChIP3 expression in Müller cell cultures under high glucose conditions and demonstrate a previously unknown interaction between the K(V)4 channel and KChIP3 in Müller cells. We show evidence for the expression of a 4-AP-sensitive transient outward voltage-gated K(+) current and an alteration in the inactivation of the macroscopic outward K(+) currents expressed in high glucose-cultured Müller cells. Our data support the notion that induction of KChIP3 and functional changes of K(V)4 channels in Müller cells could exert a physiological role in the onset of diabetic retinopathy. Copyright © 2010 Elsevier Inc. All rights reserved.

Kcne2 deletion impairs insulin secretion and causes type 2 diabetes mellitus.

PubMed

Lee, Soo Min; Baik, Jasmine; Nguyen, Dara; Nguyen, Victoria; Liu, Shiwei; Hu, Zhaoyang; Abbott, Geoffrey W

2017-06-01

Type 2 diabetes mellitus (T2DM) represents a rapidly increasing threat to global public health. T2DM arises largely from obesity, poor diet, and lack of exercise, but it also involves genetic predisposition. Here we report that the KCNE2 potassium channel transmembrane regulatory subunit is expressed in human and mouse pancreatic β cells. Kcne2 deletion in mice impaired glucose tolerance as early as 5 wk of age in pups fed a Western diet, ultimately causing diabetes. In adult mice fed normal chow, skeletal muscle expression of insulin receptor β and insulin receptor substrate 1 were down-regulated 2-fold by Kcne2 deletion, characteristic of T2DM. Kcne2 deletion also caused extensive pancreatic transcriptome changes consistent with facets of T2DM, including endoplasmic reticulum stress, inflammation, and hyperproliferation. Kcne2 deletion impaired β-cell insulin secretion in vitro up to 8-fold and diminished β-cell peak outward K + current at positive membrane potentials, but also left-shifted its voltage dependence and slowed inactivation. Interestingly, we also observed an aging-dependent reduction in β-cell outward currents in both Kcne2 +/+ and Kcne2 - / - mice. Our results demonstrate that KCNE2 is required for normal β-cell electrical activity and insulin secretion, and that Kcne2 deletion causes T2DM. KCNE2 may regulate multiple K + channels in β cells, including the T2DM-linked KCNQ1 potassium channel α subunit.-Lee, S. M., Baik, J., Nguyen, D., Nguyen, V., Liu, S., Hu, Z., Abbott, G. W. Kcne2 deletion impairs insulin secretion and causes type 2 diabetes mellitus. © FASEB.

Distributions of Li+, Na+ K+, Rb+, and Cs+ tracer ions in erythrocytes at 38 degrees C in relation to entry rates of these ions into cells at 0 degree C.

PubMed

Salminen, S; Ekman, A; Rastas, J

2000-01-01

Forces that are able to transport Na+ and K+ into two compartments were investigated. A modified Nernst-Planck equation for coupled flows of electric current, water, and ions was integrated. The result shows that if alkali ions in the ion channel of the cell membrane are separated by their electric-current-induced inward flows against an electro-osmotic outward flow of water, the logarithms of the stationary cell/medium distributions of these ions should be proportional to the inverse of their diffusion mobilities. The relationship was tested in human erythrocytes. From inward and outward movements of tracer alkali ions, calculations were made to obtain their stationary distributions at infinite time. The cell/medium distributions determined in this way at 38 degrees C are Li+ = 0.59, 22Na+ = 0.044, 42K+ = 10.0, 86Rb+ = 11.9, and 137Cs+ = 3.07. The entry rates of ions into the cell at 0 degrees C are understood to represent their diffusion mobilities in the pump channel. The entry rates are Li+ = 1.44, 2Na+ = 1, 42K+ = 2.22, 86Rb+ = 2.39, and 137Cs+ = 1.72 relative to that of 22Na+. There is an expected negative correlation between the logarithms of the stationary cell/ medium distributions at 38 degrees C and the inverse of the entry rates into the cell at 0 degrees C for the five ions. It is suggested that the proposed physical forces cause the separation of alkali ions in the channel of Na,K-ATPase.

Low resistance, large dimension entrance to the inner cavity of BK channels determined by changing side-chain volume

PubMed Central

Niu, Xiaowei

2011-01-01

Large-conductance Ca2+- and voltage-activated K+ (BK) channels have the largest conductance (250–300 pS) of all K+-selective channels. Yet, the contributions of the various parts of the ion conduction pathway to the conductance are not known. Here, we examine the contribution of the entrance to the inner cavity to the large conductance. Residues at E321/E324 on each of the four α subunits encircle the entrance to the inner cavity. To determine if 321/324 is accessible from the inner conduction pathway, we measured single-channel current amplitudes before and after exposure and wash of thiol reagents to the intracellular side of E321C and E324C channels. MPA− increased currents and MTSET+ decreased currents, with no difference between positions 321 and 324, indicating that side chains at 321/324 are accessible from the inner conduction pathway and have equivalent effects on conductance. For neutral amino acids, decreasing the size of the entrance to the inner cavity by substituting large side-chain amino acids at 321/324 decreased outward single-channel conductance, whereas increasing the size of the entrance with smaller side-chain substitutions had little effect. Reductions in outward conductance were negated by high [K+]i. Substitutions had little effect on inward conductance. Fitting plots of conductance versus side-chain volume with a model consisting of one variable and one fixed resistor in series indicated an effective diameter and length of the entrance to the inner cavity for wild-type channels of 17.7 and 5.6 Å, respectively, with the resistance of the entrance ∼7% of the total resistance of the conduction pathway. The estimated dimensions are consistent with the structure of MthK, an archaeal homologue to BK channels. Our observations suggest that BK channels have a low resistance, large entrance to the inner cavity, with the entrance being as large as necessary to not limit current, but not much larger. PMID:21576375

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

Glucose-responsive neurons in the subfornical organ of the rat--a novel site for direct CNS monitoring of circulating glucose.

PubMed

Medeiros, N; Dai, L; Ferguson, A V

2012-01-10

Glucose-sensitive neurons have been identified in a number of CNS regions including metabolic control centers of the hypothalamus. The location of these regions behind the blood-brain barrier restricts them to sensing central, but not circulating glucose concentrations. In this study, we have used patch-clamp electrophysiology to examine whether neurons in a specialized region lacking the blood-brain barrier, the subfornical organ (SFO), are also glucose sensitive. In dissociated SFO neurons, altering the bath concentration of glucose (1 mM, 5 mM, 10 mM) influenced the excitability of 49% of neurons tested (n=67). Glucose-inhibited (GI) neurons depolarized in response to decreased glucose (n=10; mean, 4.6±1.0 mV) or hyperpolarized in response to increased glucose (n=8; mean,-4.4±0.8 mV). In contrast, glucose-excited (GE) neurons depolarized in response to increased glucose (n=9; mean, 6.4±0.4 mV) or hyperpolarized in response to decreased glucose (n=6; mean,-4.8±0.6 mV). Using voltage-clamp recordings, we also identified GI (outward current to increased glucose) and GE (inward current to increased glucose) SFO neurons. The mean glucose-induced inward current had a reversal potential of -24±12 mV (n=5), while GE responses were maintained during sodium-dependent glucose transporter inhibition, supporting the conclusion that GE properties result from the activation of a nonselective cation conductance (NSCC). The glucose-induced outward current had a mean reversal potential of -78±1.2 mV (n=5), while GI responses were not observed in the presence of glibenclamide, suggesting that these properties result from the modulation of K(ATP) channels. These data demonstrate that SFO neurons are glucose responsive, further emphasizing the potential roles of this circumventricular organ as an important sensor and integrator of circulating signals of energy status. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Radiographic techniques in the explosive component facility at Sandia National Labs.

NASA Astrophysics Data System (ADS)

Lanoue, John C.

1997-05-01

The Explosive Component Facility at Sandia National Laboratory is a state of the art facility for the design and testing of energetic materials and components. Two key elements of these capabilities are the flash x-ray machines. One is a six head, 150 KeV and the other is a six head, 300 KeV instrument. One of the more interesting uses of the 150 KeV system has been to study the action and reaction of a linear shaped charge (LSC) while submerged in water. The submerged samples were viewed from the top to capture the interaction of one piece of LSC with another piece nearby. Each LSC was covered by separate rubber coverings and affixed to a composite-plate. Three heads, delayed by a specified time, were used to capture the time sequence of events in stop action. Side views of the LSC were done with and without the rubber coverings to examine the dampening effects of the cover. An end-on perspective was also captured by x-ray using one head and several time delays. The debris scatter produced from a larger device has also been examined. The explosive used was a pellet form initiated by a detonator and a timing lead. The x-ray radiographs show the particles from this device as they expand outward. Three x-ray source tubes were used in a large horizontal array, apertured to expose individual pieces of film. Another x-ray source was placed overhead and simultaneously exposed a film under the object.

Prevention of water-contamination of ethanol-saturated dentin and hydrophobic hybrid layers

PubMed Central

Sauro, Salvatore; Watson, Timothy F; Mannocci, Francesco; Tay, Franklin R; Pashley, David H

2013-01-01

SUMMARY Purpose This in vitro study evaluated the amount and the distribution of outward fluid flow that occurred when an experimental etch-and-rinse hydrophobic adhesive was applied to ethanol-saturated dentin before and after oxalate pretreatment. Materials and methods Measurements of dentin permeability were performed under a constant pulpal pressure of 20 cm H2O in deep and middle dentin. A lucifer yellow solution was placed in the pulp chamber to determine the distribution of the water contamination of the hybrid layers. Results The distribution of fluorescence in dentin specimens that were not pretreated with oxalate revealed that the dye permeated around the resin tags and filled the hybrid layer. Dentin specimens pretreated with oxalate prior to resin bonding, showed 80–83% less (p<0.05) water contamination compared to controls. The dentin permeability results obtained before and after oxalate pretreatment showed that oxalate decreased dentin permeability by 98% (p<0.05) compared to acid-etched controls. This prevented outward fluid movement during bonding resulting in better resin sealing of dentin due to the formation of a double seal of resin tags over calcium oxalate crystals in the tubules. Conclusion Outward dentinal fluid flow may contaminate hybrid layers during adhesive bonding procedures. Pretreatment of acid-etched dentin with 3% oxalic acid prior to bonding procedures can prevent outward fluid flow during bonding and water contamination of the hydrophobic hybrid layers. PMID:19701507

Development and Performance of the W/Sb2O3/KIO4/Lubricant Pyrotechnic Delay in the US Army Hand-Held Signal

DTIC Science & Technology

2013-01-01

Gany, Investigation of Slow-Propagation Tung- sten Delay Mixtures, Propellants Explos. Pyrotech. 1997, 22, 207–211. [3] Tungsten Delay Composition ...apex. This delay ele- ment then ignites an expulsion charge, which ejects and ig- nites the smoke or illumination payload. The current delay composition ...used in HHS consists of 32.0% tungsten, 56.3% barium chromate, 11.4% potassium perchlorate, and 0.3% VAAR. (All composition percentages in this

Precision digital pulse phase generator

DOEpatents

McEwan, T.E.

1996-10-08

A timing generator comprises a crystal oscillator connected to provide an output reference pulse. A resistor-capacitor combination is connected to provide a variable-delay output pulse from an input connected to the crystal oscillator. A phase monitor is connected to provide duty-cycle representations of the reference and variable-delay output pulse phase. An operational amplifier drives a control voltage to the resistor-capacitor combination according to currents integrated from the phase monitor and injected into summing junctions. A digital-to-analog converter injects a control current into the summing junctions according to an input digital control code. A servo equilibrium results that provides a phase delay of the variable-delay output pulse to the output reference pulse that linearly depends on the input digital control code. 2 figs.

Precision digital pulse phase generator

DOEpatents

McEwan, Thomas E.

1996-01-01

A timing generator comprises a crystal oscillator connected to provide an output reference pulse. A resistor-capacitor combination is connected to provide a variable-delay output pulse from an input connected to the crystal oscillator. A phase monitor is connected to provide duty-cycle representations of the reference and variable-delay output pulse phase. An operational amplifier drives a control voltage to the resistor-capacitor combination according to currents integrated from the phase monitor and injected into summing junctions. A digital-to-analog converter injects a control current into the summing junctions according to an input digital control code. A servo equilibrium results that provides a phase delay of the variable-delay output pulse to the output reference pulse that linearly depends on the input digital control code.

D-Sotalol: death by the SWORD or deserving of further consideration for clinical use?

PubMed

Doggrell, S A; Brown, L

2000-07-01

D-Sotalol is the dextro-rotatory isomer of sotalol and a class III anti-arrhythmic. D-Sotalol prolongs cardiac repolarisation by inhibiting the fast component of the delayed outward rectifying potassium channel. In animal studies, D-sotalol has been shown to be more effective in prolonging atrial, rather than ventricular, action potentials, suggesting that D-sotalol may be more effective against supra-ventricular than ventricular arrhythmias. Furthermore, in animal studies, D-sotalol induces after-depolarisations, which are predictors of pro-arrhythmic activity. D-Sotalol shows little or no reverse use dependence in animal and humans and has slow offset kinetics. This suggests that, in addition to being a preventative treatment for arrhythmias, D-sotalol may be effective at the start or during arrhythmia. As D-sotalol does not block the slow component of the delayed outward rectifying potassium channel, which is activated by the sympathetic nervous system, D-sotalol will not protect against sympathetic hyperactivity. D-Sotalol also has no effect on the K(ATP) channel, which is activated in ischaemia to shorten the action potential. Thus D-sotalol is less effective in ischaemia. Anti-arrhythmic activity with D-sotalol has been demonstrated in dog models of ventricular tachycardia and sudden death. Arrhythmias with D-sotalol have been demonstrated in an ischaemic guinea-pig ventricle model in the absence of action potentials. D-Sotalol is a weak beta-adrenoceptor antagonist and may also be a positive inotrope. In humans, D-sotalol has 100% systemic oral bioavailability, a terminal half-life of 7.2 h and is mainly excreted unchanged in the urine. Preliminary, mainly hospital-based, clinical trials showed that D-sotalol was effective in a variety of supraventricular and ventricular arrhythmias. However, a large clinical trial of D-sotalol as a preventative treatment for arrhythmias and sudden death after myocardial infarction, the SWORD trial, was terminated early because of increased mortality with D-sotalol. The group at greatest risk was those with a remote myocardial infarction and relatively good left ventricular function, the group that showed the lowest mortality when untreated. It is assumed that excessive prolongation of the action potential leading to pro-arrhythmia with D-sotalol, underlies the increased risk of death. However, there is little objective evidence in the SWORD trial to support this. Obviously D-sotalol should not be used in humans with a remote myocardial infarction and relatively good left ventricular function. D-Sotalol could still be considered for short-term hospital use in resistant arrhythmias and for longer-term use to prevent atrial fibrillation in those with remote myocardial infarction and poor left ventricular function.

A COMPARISON OF THE EFFECTS OF BRIEF RULES, A TIMER, AND PREFERRED TOYS ON SELF-CONTROL

PubMed Central

Newquist, Matthew H; Dozier, Claudia L; Neidert, Pamela L

2012-01-01

Some children make impulsive choices (i.e., choose a small but immediate reinforcer over a large but delayed reinforcer). Previous research has shown that delay fading, providing an alternative activity during the delay, teaching participants to repeat a rule during the delay, combining delay fading with an alternative activity, and combining delay fading with a countdown timer are effective for increasing self-control (i.e., choosing the large but delayed reinforcer over the small but immediate reinforcer). The purpose of the current study was to compare the effects of various interventions in the absence of delay fading (i.e., providing brief rules, providing a countdown timer during the delay, or providing preferred toys during the delay) on self-control. Results suggested that providing brief rules or a countdown timer during the delay was ineffective for enhancing self-control. However, providing preferred toys during the delay effectively enhanced self-control. PMID:23060664

A comparison of the effects of brief rules, a timer, and preferred toys on self-control.

PubMed

Newquist, Matthew H; Dozier, Claudia L; Neidert, Pamela L

2012-01-01

Some children make impulsive choices (i.e., choose a small but immediate reinforcer over a large but delayed reinforcer). Previous research has shown that delay fading, providing an alternative activity during the delay, teaching participants to repeat a rule during the delay, combining delay fading with an alternative activity, and combining delay fading with a countdown timer are effective for increasing self-control (i.e., choosing the large but delayed reinforcer over the small but immediate reinforcer). The purpose of the current study was to compare the effects of various interventions in the absence of delay fading (i.e., providing brief rules, providing a countdown timer during the delay, or providing preferred toys during the delay) on self-control. Results suggested that providing brief rules or a countdown timer during the delay was ineffective for enhancing self-control. However, providing preferred toys during the delay effectively enhanced self-control.

Modulating endogenous electric currents in human corneal wounds--a novel approach of bioelectric stimulation without electrodes.

PubMed

Reid, Brian; Graue-Hernandez, Enrique O; Mannis, Mark J; Zhao, Min

2011-03-01

To measure electric current in human corneal wounds and test the feasibility of pharmacologically enhancing the current to promote corneal wound healing. Using a noninvasive vibrating probe, corneal electric current was measured before and after wounding of the epithelium of donated postmortem human corneas. The effects of drug aminophylline and chloride-free solution on wound current were also tested. Unwounded cornea had small outward currents (0.07 μA/cm²). Wounding increased the current more than 5 fold (0.41 μA/cm²). Monitoring the wound current over time showed that it seemed to be actively regulated and maintained above normal unwounded levels for at least 6 hours. The time course was similar to that previously measured in rat cornea. Drug treatment or chloride-free solution more than doubled the size of wound currents. Electric current at human corneal wounds can be significantly increased with aminophylline or chloride-free solution. Because corneal wound current directly correlates with wound healing rate, our results suggest a role for chloride-free and/or aminophylline eyedrops to enhance healing of damaged cornea in patients with reduced wound healing such as the elderly or diabetic patient. This novel approach offers bioelectric stimulation without electrodes and can be readily tested in patients.

Intensity coding in electric hearing: effects of electrode configurations and stimulation waveforms.

PubMed

Chua, Tiffany Elise H; Bachman, Mark; Zeng, Fan-Gang

2011-01-01

Current cochlear implants typically stimulate the auditory nerve with biphasic pulses and monopolar electrode configurations. Tripolar stimulation can increase spatial selectivity and potentially improve place pitch related perception but requires higher current levels to elicit the same loudness as monopolar stimulation. The present study combined delayed pseudomonophonasic pulses, which produce lower thresholds, with tripolar stimulation in an attempt to solve the power-performance tradeoff problem. The present study systematically measured thresholds, dynamic range, loudness growth, and intensity discrimination using either biphasic or delayed pseudomonophonasic pulses under both monopolar and tripolar stimulation. Participants were five Clarion cochlear implant users. For each subject, data from apical, middle, and basal electrode positions were collected when possible. Compared with biphasic pulses, delayed pseudomonophonasic pulses increased the dynamic range by lowering thresholds while maintaining comparable maximum allowable levels under both electrode configurations. However, delayed pseudomonophonasic pulses did not change the shape of loudness growth function and actually increased intensity discrimination limens, especially at lower current levels. The present results indicate that delayed pseudomonophonasic pulses coupled with tripolar stimulation cannot provide significant power savings nor can it increase the functional dynamic range. Whether this combined stimulation could improve functional spectral resolution remains to be seen.

Differential roles of two delayed rectifier potassium currents in regulation of ventricular action potential duration and arrhythmia susceptibility.

PubMed

Devenyi, Ryan A; Ortega, Francis A; Groenendaal, Willemijn; Krogh-Madsen, Trine; Christini, David J; Sobie, Eric A

2017-04-01

Arrhythmias result from disruptions to cardiac electrical activity, although the factors that control cellular action potentials are incompletely understood. We combined mathematical modelling with experiments in heart cells from guinea pigs to determine how cellular electrical activity is regulated. A mismatch between modelling predictions and the experimental results allowed us to construct an improved, more predictive mathematical model. The balance between two particular potassium currents dictates how heart cells respond to perturbations and their susceptibility to arrhythmias. Imbalances of ionic currents can destabilize the cardiac action potential and potentially trigger lethal cardiac arrhythmias. In the present study, we combined mathematical modelling with information-rich dynamic clamp experiments to determine the regulation of action potential morphology in guinea pig ventricular myocytes. Parameter sensitivity analysis was used to predict how changes in ionic currents alter action potential duration, and these were tested experimentally using dynamic clamp, a technique that allows for multiple perturbations to be tested in each cell. Surprisingly, we found that a leading mathematical model, developed with traditional approaches, systematically underestimated experimental responses to dynamic clamp perturbations. We then re-parameterized the model using a genetic algorithm, which allowed us to estimate ionic current levels in each of the cells studied. This unbiased model adjustment consistently predicted an increase in the rapid delayed rectifier K + current and a drastic decrease in the slow delayed rectifier K + current, and this prediction was validated experimentally. Subsequent simulations with the adjusted model generated the clinically relevant prediction that the slow delayed rectifier is better able to stabilize the action potential and suppress pro-arrhythmic events than the rapid delayed rectifier. In summary, iterative coupling of simulations and experiments enabled novel insight into how the balance between cardiac K + currents influences ventricular arrhythmia susceptibility. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Factors associated with long diagnostic delay in celiac disease.

PubMed

Fuchs, Valma; Kurppa, Kalle; Huhtala, Heini; Collin, Pekka; Mäki, Markku; Kaukinen, Katri

2014-11-01

Here, we investigated the factors associated with long diagnostic delay in celiac disease and the impact of the national Current Care Guidelines in reducing the delay. This population-based study involved 825 adult celiac disease patients. The diagnosis was considered delayed when the interval between first symptoms and diagnosis was >10 years. The patients were asked about the duration and type of symptoms before diagnosis, time and site (tertiary, secondary, or primary care) of the diagnosis, family history of the disease, and presence of significant comorbidities. Analysis was performed by binary logistic regression. Altogether, 261 (32%) out of 825 participants reported a diagnostic delay of >10 years. Female gender, neurological or musculoskeletal disorders and presence of diarrhea, abdominal pain, and malabsorption were associated with prolonged delay. Male gender, diagnosis after the introduction of the first Current Care Guidelines in 1997, and being detected by serological screening, and family history of celiac disease were associated with a lower risk of delayed diagnosis. Factors not associated with the delay were site of diagnosis, age, and presence of dermatitis herpetiformis, type 1 diabetes, or thyroidal disease. The number of long diagnostic delays in celiac disease has decreased over the past decades. The shift of diagnostics from secondary and tertiary care to primary care has not been detrimental. National guidelines together with increased awareness and active screening in at-risk groups of celiac disease are important in these circumstances.

Latitude-dependent delay in the responses of the equatorial electrojet and Sq currents to X-class solar flares

NASA Astrophysics Data System (ADS)

Nogueira, Paulo A. B.; Abdu, Mangalathayil A.; Souza, Jonas R.; Denardini, Clezio M.; Barbosa Neto, Paulo F.; Serra de Souza da Costa, João P.; Silva, Ana P. M.

2018-01-01

We have analyzed low-latitude ionospheric current responses to two intense (X-class) solar flares that occurred on 13 May 2013 and 11 March 2015. Sudden intensifications, in response to solar flare radiation impulses, in the Sq and equatorial electrojet (EEJ) currents, as detected by magnetometers over equatorial and low-latitude sites in South America, are studied. In particular we show for the first time that a 5 to 8 min time delay is present in the peak effect in the EEJ, with respect that of Sq current outside the magnetic equator, in response to the flare radiation enhancement. The Sq current intensification peaks close to the flare X-ray peak, while the EEJ peak occurs 5 to 8 min later. We have used the Sheffield University Plasmasphere-Ionosphere Model at National Institute for Space Research (SUPIM-INPE) to simulate the E-region conductivity enhancement as caused by the flare enhanced solar extreme ultraviolet (EUV) and soft X-rays flux. We propose that the flare-induced enhancement in neutral wind occurring with a time delay (with respect to the flare radiation) could be responsible for a delayed zonal electric field disturbance driving the EEJ, in which the Cowling conductivity offers enhanced sensitivity to the driving zonal electric field.

Modeling of synchronization behavior of bursting neurons at nonlinearly coupled dynamical networks.

PubMed

Çakir, Yüksel

2016-01-01

Synchronization behaviors of bursting neurons coupled through electrical and dynamic chemical synapses are investigated. The Izhikevich model is used with random and small world network of bursting neurons. Various currents which consist of diffusive electrical and time-delayed dynamic chemical synapses are used in the simulations to investigate the influences of synaptic currents and couplings on synchronization behavior of bursting neurons. The effects of parameters, such as time delay, inhibitory synaptic strengths, and decay time on synchronization behavior are investigated. It is observed that in random networks with no delay, bursting synchrony is established with the electrical synapse alone, single spiking synchrony is observed with hybrid coupling. In small world network with no delay, periodic bursting behavior with multiple spikes is observed when only chemical and only electrical synapse exist. Single-spike and multiple-spike bursting are established with hybrid couplings. A decrease in the synchronization measure is observed with zero time delay, as the decay time is increased in random network. For synaptic delays which are above active phase period, synchronization measure increases with an increase in synaptic strength and time delay in small world network. However, in random network, it increases with only an increase in synaptic strength.

USAF 1990 Research Initiation Program. Volume 3

DTIC Science & Technology

1992-06-25

the reinforcement outward, both on the entrance and exit sides. The reinforcement was bent outward like a membrane under internal prressure. This led...potential of a neuron. C: cell capacitance. R: membrane resistance. w: synaptic weight. h(x): sigmoidal function describing the firing rate. y: external...Proof: The uncertain closed loop plant may be written as x(t)=(A+AA)x(t)+(Ao+ AAo )x(t-T) (B+AB)F(C AC)x(t) =(A+BFC)x(t)+(AA+ABFC+BFAC+ABFAC)x(t)+(Ao+Ao)X(t

MEMS Micro-Translation Device with Improved Linear Travel Capability

NASA Technical Reports Server (NTRS)

Abushagur, Mustafa A. G. (Inventor); Ferguson, Cynthia K. (Inventor); Nordin, Gregory P. (Inventor); English, Jennifer M. (Inventor)

2007-01-01

A microscopic translation device for a microelectromechanical system includes a pair of linear stator assemblies disposed in spaced relation to define an elongate channel. Each assembly is formed by a plurality of stators arranged in a row along the channel. A shuttle member is disposed between the stator assemblies for translating movement along the channel. The shuttle member includes a plurality of rotors extending outwardly from opposite sides. The shuttle is grounded through the stator assemblies and includes a mounting area for an object to be translated. Electrical lines are individually connected to alternate stators of a plurality of groups of the stators. A current supply sequentially supplies current through the electrical lines to the alternate stators so as to effect charging of the stators in a predetermined sequence. This produces a tangential capacitive force that causes translation of the shuttle.

Resonant spin wave excitations in a magnonic crystal cavity

NASA Astrophysics Data System (ADS)

Kumar, N.; Prabhakar, A.

2018-03-01

Spin polarized electric current, injected into permalloy (Py) through a nano contact, exerts a torque on the magnetization. The spin waves (SWs) thus excited propagate radially outward. We propose an antidot magnonic crystal (MC) with a three-hole defect (L3) around the nano contact, designed so that the frequency of the excited SWs, lies in the band gap of the MC. L3 thus acts as a resonant SW cavity. The energy in this magnonic crystal cavity can be tapped by an adjacent MC waveguide (MCW). An analysis of the simulated micromagnetic power spectrum, at the output port of the MCW reveals stable SW oscillations. The quality factor of the device, calculated using the decay method, was estimated as Q > 105 for an injected spin current density of 7 ×1012 A/m2.

Blockade of HERG human K+ channel and IKr of guinea pig cardiomyocytes by prochlorperazine.

PubMed

Kim, Moon-Doo; Eun, Su-Yong; Jo, Su-Hyun

2006-08-21

Prochlorperazine, a drug for the symptomatic control of nausea, vomiting and psychiatric disorders, can induce prolonged QT, torsades de pointes and sudden death. We studied the effects of prochlorperazine on human ether-a-go-go-related gene (HERG) channels expressed in Xenopus oocytes and also in the delayed rectifier K+ current of guinea pig cardiomyocytes. Prochlorperazine induced a concentration-dependent decrease in current amplitudes at the end of the voltage steps and tail currents of HERG. The IC50 for a prochlorperazine block of HERG current in Xenopus oocytes progressively decreased relative to the degree of depolarization, from 42.1 microM at -40 mV to 37.4 microM at 0 mV to 22.6 microM at +40 mV. The block of HERG by prochlorperazine was use-dependent, exhibiting a more rapid onset and a greater steady-state block at higher frequencies of activation, while there was partial relief of the block with reduced frequencies. In guinea pig ventricular myocytes, bath applications of 0.5 and 1 muM prochlorperazine at 36 degrees C blocked rapidly activating delayed rectifier K+ current by 38.9% and 76.5%, respectively, but did not significantly block slowly activating delayed rectifier K+ current. Our findings suggest that the arrhythmogenic side effects of prochlorperazine are caused by a blockade of HERG and the rapid component of the delayed rectifier K+ current rather than by a blockade of the slow component.

[Delays in diagnosing and treating tuberculosis in Croatia].

PubMed

Jurčev-Savičević, Anamarija; Popović-Grle, Sanja; Mulić, Rosanda; Smoljanović, Mladen; Miše, Kornelija

2012-09-01

The aim of this study was to determine factors causing delay in tuberculosis diagnosis and treatment in Croatia. It included 240 adults with pulmonary tuberculosis, who were interviewed for demographics, socioeconomic, lifestyle, and personal health data. Total delay was defined as a number of days from the onset of symptoms to the initiation of therapy. The median and the 75th percentile of the total delay were 68 and 120 days, respectively: 16.7 % of the patients initiated treatment within the first month, 23.8 % within the second month, 23.3 % within the third month, 12.9 % within the fourth month, and 23.3 % more than four months after the symptoms appeared. Long delay (exceeding median delay) was strongly associated with drug abuse (p=0.021). Extreme delay (75th percentile of delay) was significantly associated with the lowest level of education (p=0.021), below minimal income (p=0.039), minimal to average income (p=0.020), current smoking (p=0.050), and co-morbidity (p=0.048). In the multivariate model, long delay remained associated with drug abuse, while extreme delay was associated with the lowest level of education (p=0.033) and current (p=0.017) and ex-smoking (p=0.045).In a setting with decreasing TB incidence, the reported delay can be reduced by increasing health education, not only about tuberculosis per se, but about health in general and attitudes towards prevention and early care. It is also important to increase tuberculosis knowledge among healthcare workers as well as their diagnostic skills.

Engine Lubricant

NASA Technical Reports Server (NTRS)

1993-01-01

PS 212, a plasma-sprayed coating developed by NASA, is used to coat valves in a new rotorcam engine. The coating eliminates the need for a liquid lubricant in the rotorcam, which has no crankshaft, flywheel, distributor or water pump. Developed by Murray United Development Corporation, it is a rotary engine only 10 inches long with four cylinders radiating outward from a central axle. Company officials say the engine will be lighter, more compact and cheaper to manufacture than current engines and will feature cleaner exhaust emissions. A licensing arrangement with a manufacturer is under negotiation. Primary applications are for automobiles, but the engine may also be used in light aircraft.

In situ Observations of Heliospheric Current Sheets Evolution

NASA Astrophysics Data System (ADS)

Liu, Yong; Peng, Jun; Huang, Jia; Klecker, Berndt

2017-04-01

We investigate the Heliospheric current sheet observation time difference of the spacecraft using the STEREO, ACE and WIND data. The observations are first compared to a simple theory in which the time difference is only determined by the radial and longitudinal separation between the spacecraft. The predictions fit well with the observations except for a few events. Then the time delay caused by the latitudinal separation is taken in consideration. The latitude of each spacecraft is calculated based on the PFSS model assuming that heliospheric current sheets propagate at the solar wind speed without changing their shapes from the origin to spacecraft near 1AU. However, including the latitudinal effects does not improve the prediction, possibly because that the PFSS model may not locate the current sheets accurately enough. A new latitudinal delay is predicted based on the time delay using the observations on ACE data. The new method improved the prediction on the time lag between spacecraft; however, further study is needed to predict the location of the heliospheric current sheet more accurately.

Dancing sprites: Detailed analysis of two case studies

NASA Astrophysics Data System (ADS)

Soula, Serge; Mlynarczyk, Janusz; Füllekrug, Martin; Pineda, Nicolau; Georgis, Jean-François; van der Velde, Oscar; Montanyà, Joan; Fabró, Ferran

2017-03-01

On 29-30 October 2013, a low-light video camera installed at Pic du Midi (2877 m), recorded transient luminous events above a very active storm over the Mediterranean Sea. The minimum cloud top temperature reached -73°C, while its cloud to ground (CG) flash rate exceeded 30 fl min-1. Some sprite events have long duration and resemble to dancing sprites. We analyze in detail the temporal evolution and estimated location of two series of sprite sequences, as well as the cloud structure, the lightning activity, the electric field radiated in a broad range of low frequencies, and the current moment waveform of the lightning strokes. (i) In each series, successive sprite sequences reflect time and location of corresponding positive lightning strokes across the stratiform region. (ii) The longer time-delayed (>20 ms) sprite elements correspond to the lower impulsive charge moment changes (iCMC) of the parent strokes (<200 C km), and they are shifted few tens of kilometers from their SP + CG stroke. However, both short and long time-delayed sprite elements also occur after strokes that produce a large iCMC and that are followed by a continuing current. (iii) The long time-delayed sprite elements during the continuing current correspond to surges in the current moment waveform. They occur sometimes at an altitude apparently lower than the previous short time-delayed sprite elements, possibly because of changes in the local conductivity. (iv) The largest and brightest sprite elements produce significant current signatures, visible when their delay is not too short ( 3-5 ms).

Why Do Rereading Lag Effects Depend on Test Delay?

ERIC Educational Resources Information Center

Rawson, Katherine A.

2012-01-01

In previous research, rereading after a long lag versus a short lag led to greater performance on delayed tests but not on immediate tests. The current study tested two accounts of why the effects of rereading lag depend on test delay. The "levels of representation" ("LOR") "hypothesis" states that the effects reflect…

Comparing Active Delay and Procrastination from a Self-Regulated Learning Perspective

ERIC Educational Resources Information Center

Corkin, Danya M.; Yu, Shirley L.; Lindt, Suzanne F.

2011-01-01

Researchers have proposed that the act of postponing academic work may be divided into a traditional definition of procrastination, viewed as maladaptive, and adaptive forms of delay. Adaptive forms of delay may be more consistent with certain facets of self-regulated learning. The current study investigated this issue by examining whether the…

GLOBAL HIGH-RESOLUTION N-BODY SIMULATION OF PLANET FORMATION. I. PLANETESIMAL-DRIVEN MIGRATION

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

Kominami, J. D.; Daisaka, H.; Makino, J.

2016-03-01

We investigated whether outward planetesimal-driven migration (PDM) takes place or not in simulations when the self-gravity of planetesimals is included. We performed N-body simulations of planetesimal disks with a large width (0.7–4 au) that ranges over the ice line. The simulations consisted of two stages. The first-stage simulations were carried out to see the runaway growth phase using the planetesimals of initially the same mass. The runaway growth took place both at the inner edge of the disk and at the region just outside the ice line. This result was utilized for the initial setup of the second-stage simulations, in which themore » runaway bodies just outside the ice line were replaced by the protoplanets with about the isolation mass. In the second-stage simulations, the outward migration of the protoplanet was followed by the stopping of the migration due to the increase of the random velocity of the planetesimals. Owing to this increase of random velocities, one of the PDM criteria derived in Minton and Levison was broken. In the current simulations, the effect of the gas disk is not considered. It is likely that the gas disk plays an important role in PDM, and we plan to study its effect in future papers.« less

Bimodal voltage dependence of TRPA1: mutations of a key pore helix residue reveal strong intrinsic voltage-dependent inactivation.

PubMed

Wan, Xia; Lu, Yungang; Chen, Xueqin; Xiong, Jian; Zhou, Yuanda; Li, Ping; Xia, Bingqing; Li, Min; Zhu, Michael X; Gao, Zhaobing

2014-07-01

Transient receptor potential A1 (TRPA1) is implicated in somatosensory processing and pathological pain sensation. Although not strictly voltage-gated, ionic currents of TRPA1 typically rectify outwardly, indicating channel activation at depolarized membrane potentials. However, some reports also showed TRPA1 inactivation at high positive potentials, implicating voltage-dependent inactivation. Here we report a conserved leucine residue, L906, in the putative pore helix, which strongly impacts the voltage dependency of TRPA1. Mutation of the leucine to cysteine (L906C) converted the channel from outward to inward rectification independent of divalent cations and irrespective to stimulation by allyl isothiocyanate. The mutant, but not the wild-type channel, displayed exclusively voltage-dependent inactivation at positive potentials. The L906C mutation also exhibited reduced sensitivity to inhibition by TRPA1 blockers, HC030031 and ruthenium red. Further mutagenesis of the leucine to all natural amino acids individually revealed that most substitutions at L906 (15/19) resulted in inward rectification, with exceptions of three amino acids that dramatically reduced channel activity and one, methionine, which mimicked the wild-type channel. Our data are plausibly explained by a bimodal gating model involving both voltage-dependent activation and inactivation of TRPA1. We propose that the key pore helix residue, L906, plays an essential role in responding to the voltage-dependent gating.

Mass loss at Saturn: The contribution of plasmoids

NASA Astrophysics Data System (ADS)

Kivelson, M.; Jia, X.; Jackman, C. M.

2017-12-01

Jia and Kivelson (2012) showed that an MHD simulation of Saturn's magnetosphere including rotating field-aligned currents generates a plasmoid on each rotation period. For southern summer conditions, plasmoids form through reconnection in the tail near midnight at a rotation phase for which the core magnetic field perturbation points towards the planet in the LT sector of the release. After release, they move northward and outward in the post midnight sector. Mass loss is found to be dominated by plasmoid release, and to compare closely to the mass source rate; much of the outward mass flux is found in the 0300-0900 LT sector. However, studies of plasmoid signatures in Cassini magnetometer data conclude that releases do not occur each rotation period and infer mass loss rates far smaller than Saturn's mass source rate (Jackman et al., 2014). Studies based on plasma data also infer loss rates smaller than the source rate from Enceladus (Thomsen, 2013). The simulation suggests that plasmoid occurrence frequency depends strongly on local time and latitude. Indeed, in regions near the equator and near midnight, where plasmoids are present in the simulation, the occurrence frequency of plasmoid releases inferred from magnetometer data is higher than elsewhere (Jackman et al., 2016; Smith et al., 2016), with occurrence probability peaking at the phase predicted by the simulation. We consider how the observational limitations should be modified to establish mass loss rates and plasmoid occurrence frequency.

Torques Induced by Scattered Pebble-flow in Protoplanetary Disks

NASA Astrophysics Data System (ADS)

Benítez-Llambay, Pablo; Pessah, Martin E.

2018-03-01

Fast inward migration of planetary cores is a common problem in the current planet formation paradigm. Even though dust is ubiquitous in protoplanetary disks, its dynamical role in the migration history of planetary embryos has not been assessed. In this Letter, we show that the scattered pebble-flow induced by a low-mass planetary embryo leads to an asymmetric dust-density distribution that is able to exert a net torque. By analyzing a large suite of multifluid hydrodynamical simulations addressing the interaction between the disk and a low-mass planet on a fixed circular orbit, and neglecting dust feedback onto the gas, we identify two different regimes, gas- and gravity-dominated, where the scattered pebble-flow results in almost all cases in positive torques. We collect our measurements in a first torque map for dusty disks, which will enable the incorporation of the effect of dust dynamics on migration into population synthesis models. Depending on the dust drift speed, the dust-to-gas mass ratio/distribution, and the embryo mass, the dust-induced torque has the potential to halt inward migration or even induce fast outward migration of planetary cores. We thus anticipate that dust-driven migration could play a dominant role during the formation history of planets. Because dust torques scale with disk metallicity, we propose that dust-driven outward migration may enhance the occurrence of distant giant planets in higher-metallicity systems.

Inward Lithium-Ion Breathing of Hierarchically Porous Silicon Anodes

DOE PAGES

Xiao, Qiangfeng; Gu, Meng; Yang, Hui; ...

2015-11-05

Silicon has been identified as one of the most promising candidates as anode for high performance lithium-ion batteries. The key challenge for Si anodes is the large volume change induced chemomechanical fracture and subsequent rapid capacity fading upon cyclic charge and discharge. Improving capacity retention thus critically relies on smart accommodation of the volume changes through nanoscale structural design. In this work, we report a novel fabrication method for hierarchically porous Si nanospheres (hp-SiNSs), which consist of a porous shell and a hollow core. Upon charge/discharge cycling, the hp-SiNSs accommodate the volume change through reversible inward expansion/contraction with negligible particle-levelmore » outward expansion. Our mechanics analysis revealed that such a unique volume-change accommodation mechanism is enabled by the much stiffer modulus of the lithiated layer than the unlithiated porous layer and the low flow stress of the porous structure. Such inward expansion shields the hp-SiNSs from fracture, opposite to the outward expansion in solid Si during lithiation. Lithium ion battery assembled with this new nanoporous material exhibits high capacity, high power, long cycle life and high coulombic efficiency, which is superior to the current commercial Si-based anode materials. We find the low cost synthesis approach reported here provides a new avenue for the rational design of hierarchically porous structures with unique materials properties.« less

Experimental constraints on impact-induced winds

NASA Astrophysics Data System (ADS)

Quintana, Stephanie N.; Schultz, Peter H.; Horowitz, Seth S.

2018-05-01

A new class of wind streaks on Mars uniquely associated with impact craters is most clearly detected in nighttime thermal infrared imaging. Thermally bright streaks radiate from some well-preserved impact craters and are related to the impact process. Using laboratory experiments performed at the NASA Ames Vertical Gun Range, we test the hypothesis that these streaks are formed from either the winds within an air-blast or winds set up by expanding impact vapor interacting with the atmosphere. The experiments use a variety of tracers and instruments to document three interrelated processes occurring in the impact of a Pyrex projectile into an easily vaporized powdered dolomite target: (1) a surface roughening spreading outward from the impact point, (2) an expanding vapor plume, and (3) outward winds made visible by dust trails from vertically placed, dusty pipe cleaners. The clear connection between the surface roughening, vapor expansion, and outward winds implicate an expanding vapor interacting with the atmosphere as the controlling process.

SELF-SUSTAINED RECYCLING IN THE INNER DUST RING OF PRE-TRANSITIONAL DISKS

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

Husmann, T.; Loesche, C.; Wurm, G., E-mail: tim.jankowski@uni-due.de

Observations of pre-transitional disks show a narrow inner dust ring and a larger outer one. They are separated by a cavity with no or only little dust. We propose an efficient recycling mechanism for the inner dust ring which keeps it in a steady state. No major particle sources are needed for replenishment. Dust particles and pebbles drift outwards by radiation pressure and photophoresis. The pebbles grow during outward drift until they reach a balanced position where residual gravity compensates photophoresis. While still growing larger they reverse their motion and drift inward. Eventually, their speed is fast enough for themmore » to be destroyed in collisions with other pebbles and drift outward again. We quantify the force balance and drift velocities for the disks LkCa15 and HD 135344B. We simulate single-particle evolution and show that this scenario is viable. Growth and drift timescales are on the same order and a steady state can be established in the inner dust ring.« less

Classical confinement and outward convection of impurity ions in the MST RFP

NASA Astrophysics Data System (ADS)

Kumar, S. T. A.; Den Hartog, D. J.; Mirnov, V. V.; Caspary, K. J.; Magee, R. M.; Brower, D. L.; Chapman, B. E.; Craig, D.; Ding, W. X.; Eilerman, S.; Fiksel, G.; Lin, L.; Nornberg, M.; Parke, E.; Reusch, J. A.; Sarff, J. S.

2012-05-01

Impurity ion dynamics measured with simultaneously high spatial and temporal resolution reveal classical ion transport in the reversed-field pinch. The boron, carbon, oxygen, and aluminum impurity ion density profiles are obtained in the Madison Symmetric Torus [R. N. Dexter et al., Fusion Technol. 19, 131 (1991)] using a fast, active charge-exchange-recombination-spectroscopy diagnostic. Measurements are made during improved-confinement plasmas obtained using inductive control of tearing instability to mitigate stochastic transport. At the onset of the transition to improved confinement, the impurity ion density profile becomes hollow, with a slow decay in the core region concurrent with an increase in the outer region, implying an outward convection of impurities. Impurity transport from Coulomb collisions in the reversed-field pinch is classical for all collisionality regimes, and analysis shows that the observed hollow profile and outward convection can be explained by the classical temperature screening mechanism. The profile agrees well with classical expectations. Experiments performed with impurity pellet injection provide further evidence for classical impurity ion confinement.

What's in and what's out in branding? A novel articulation effect for brand names.

PubMed

Topolinski, Sascha; Zürn, Michael; Schneider, Iris K

2015-01-01

The present approach exploits the biomechanical connection between articulation and ingestion-related mouth movements to introduce a novel psychological principle of brand name design. We constructed brand names for diverse products with consonantal stricture spots either from the front to the rear of the mouth, thus inwards (e.g., BODIKA), or from the rear to the front, thus outwards (e.g., KODIBA). These muscle dynamics resemble the oral kinematics during either ingestion (inwards), which feels positive, or expectoration (outwards), which feels negative. In 7 experiments (total N = 1261), participants liked products with inward names more than products with outward names (Experiment 1), reported higher purchase intentions (Experiment 2), and higher willingness-to-pay (Experiments 3a-3c, 4, 5), with the price gain amounting to 4-13% of the average estimated product value. These effects occurred across English and German language, under silent reading, for both edible and non-edible products, and even in the presence of a much stronger price determinant, namely fair-trade production (Experiment 5).

The articulatory in-out effect resists oral motor interference.

PubMed

Lindau, Berit; Topolinski, Sascha

2018-02-01

People prefer words with inward directed consonantal patterns (e.g., MENIKA) compared to outward patterns (KENIMA), because inward (outward) articulation movements resemble positive (negative) mouth actions such as swallowing (spitting). This effect might rely on covert articulation simulations, or subvocalizations, since it occurs also under silent reading. We tested to what degree these underlying articulation simulations are disturbed by oral motor interference. In 3 experiments (total N = 465) we interfered with these articulation simulations by employing concurrent oral exercises that induce oral motor noise while judging inward and outward words (chewing gum, Experiment 1; executing meaningless tongue movements, Experiment 2; concurrent verbalizations, Experiment 3). Across several word stimulus types, the articulatory in-out effect was not modulated by these tasks. This finding introduces a theoretically interesting case, because in contrast to many previous demonstrations regarding other motor-preference effects, the covert simulations in this effect are not susceptible to selective motor interference. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Impulsive aggression, delay discounting, and adolescent suicide attempts: effects of current psychotropic medication use and family history of suicidal behavior.

PubMed

Bridge, Jeffrey A; Reynolds, Brady; McBee-Strayer, Sandra M; Sheftall, Arielle H; Ackerman, John; Stevens, Jack; Mendoza, Kristen; Campo, John V; Brent, David A

2015-03-01

Impulsive-aggressive behaviors have been consistently implicated in the phenomenology, neurobiology, and familial aggregation of suicidal behavior. The purpose of this study was to extend previous work by examining laboratory behavioral measures of delayed reward impulsivity and impulsive aggression in adolescent suicide attempters and never-suicidal comparison subjects. Using the Point Subtraction Aggression Paradigm (PSAP) and the Delay Discounting Task (DDQ), the authors examined delay discounting and impulsive aggression in 40 adolescent suicide attempters, ages 13-18, and 40 never-suicidal, demographically matched psychiatric comparison subjects. Overall, suicide attempters and comparison subjects performed similarly on the PSAP and DDQ. There was a significant group by current psychotropic medication use interaction (p=0.013) for mean aggressive responses on the PSAP. Group comparisons revealed that attempters emitted more aggressive responses per provocation than comparison subjects, only in those not on psychotropic medication (p=0.049), whereas for those currently treated with psychotropic medication, there were no group differences (p>0.05). This interaction effect was specific to current antidepressant use. Among all subjects, family history of suicidal behavior (suicide or suicide attempt) in first degree relatives was significantly correlated with both delay discounting (r=-0.22, p=0.049), and aggressive responding (r=0.27, p=0.015). Family history of suicidal behavior was associated with delay discounting, but not with aggressive responding on the PSAP, after controlling for relevant covariates. In this study, impulsive-aggressive responding was associated with suicide attempt only in those not being treated with antidepressants. Future work to replicate and extend these findings could have important therapeutic implications for the treatment of depressed suicide attempters, many of whom are affected by impulsive aggression.

Impulsive Aggression, Delay Discounting, and Adolescent Suicide Attempts: Effects of Current Psychotropic Medication Use and Family History of Suicidal Behavior

PubMed Central

Reynolds, Brady; McBee-Strayer, Sandra M.; Sheftall, Arielle H.; Ackerman, John; Stevens, Jack; Mendoza, Kristen; Campo, John V.; Brent, David A.

2015-01-01

Abstract Objective: Impulsive-aggressive behaviors have been consistently implicated in the phenomenology, neurobiology, and familial aggregation of suicidal behavior. The purpose of this study was to extend previous work by examining laboratory behavioral measures of delayed reward impulsivity and impulsive aggression in adolescent suicide attempters and never-suicidal comparison subjects. Methods: Using the Point Subtraction Aggression Paradigm (PSAP) and the Delay Discounting Task (DDQ), the authors examined delay discounting and impulsive aggression in 40 adolescent suicide attempters, ages 13–18, and 40 never-suicidal, demographically matched psychiatric comparison subjects. Results: Overall, suicide attempters and comparison subjects performed similarly on the PSAP and DDQ. There was a significant group by current psychotropic medication use interaction (p=0.013) for mean aggressive responses on the PSAP. Group comparisons revealed that attempters emitted more aggressive responses per provocation than comparison subjects, only in those not on psychotropic medication (p=0.049), whereas for those currently treated with psychotropic medication, there were no group differences (p>0.05). This interaction effect was specific to current antidepressant use. Among all subjects, family history of suicidal behavior (suicide or suicide attempt) in first degree relatives was significantly correlated with both delay discounting (r=−0.22, p=0.049), and aggressive responding (r=0.27, p=0.015). Family history of suicidal behavior was associated with delay discounting, but not with aggressive responding on the PSAP, after controlling for relevant covariates. Conclusions: In this study, impulsive-aggressive responding was associated with suicide attempt only in those not being treated with antidepressants. Future work to replicate and extend these findings could have important therapeutic implications for the treatment of depressed suicide attempters, many of whom are affected by impulsive aggression. PMID:25745870

Anion exchange pathways for Cl sup minus transport in rabbit renal microvillus membranes

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

Karniski, L.P.; Aronson, P.S.

1987-09-01

The authors evaluated the mechanisms of chloride transport in microvillus membrane vesicles isolated from the rabbit renal cortex. The presence of Cl-formate exchange was confirmed. Outward gradients of oxaloacetate, HCO{sub 3}, acetate, lactate, succinate, sulfate, and p-aminohippurate (PAH) stimulated the rate of Cl uptake minimally or not at all. However, an outward gradient of oxalate stimulated Cl uptake by 70%, and an outward Cl gradient induced uphill oxalate uptake, indicting Cl-oxalate exchange. Moreover, an outward formate gradient induced uphill oxalate uptake, indicating formate-oxalate exchange. Studies of inhibitor and substrate specificity indicated the probably operation of at least two separate anionmore » exchangers in mediating Cl transport. The Cl-formate exchanger accepted Cl and formate as substrates, had little or no affinity for oxalate, was sensitive to inhibition by furosemide, and was less sensitive to inhibition by 4,4{prime}-diisothiocyanostilbene-2,2{prime}-disulfonic acid (DIDS). The Cl (formate)-oxalate exchanger also accepted Cl and formate as substrates but had high affinity for oxalate, was highly sensitive to inhibition by DIDS, and was less sensitive to inhibition by furosemide. The Cl-formate exchanger was electroneutral, whereas the Cl (formate)-oxalate exchanger was electrogenic. They conclude that at least separate anion exchangers mediating Cl transport are present on the luminal membrane of the rabbit proximal tubule cell. These exchangers may play important roles in mediating transtubular Cl and oxalate transport in this nephron segment.« less

OUTWARD MOTION OF POROUS DUST AGGREGATES BY STELLAR RADIATION PRESSURE IN PROTOPLANETARY DISKS

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

Tazaki, Ryo; Nomura, Hideko, E-mail: rtazaki@kusastro.kyoto-u.ac.jp

2015-02-01

We study the dust motion at the surface layer of protoplanetary disks. Dust grains in the surface layer migrate outward owing to angular momentum transport via gas-drag force induced by the stellar radiation pressure. In this study we calculate the mass flux of the outward motion of compact grains and porous dust aggregates by the radiation pressure. The radiation pressure force for porous dust aggregates is calculated using the T-Matrix Method for the Clusters of Spheres. First, we confirm that porous dust aggregates are forced by strong radiation pressure even if they grow to be larger aggregates, in contrast tomore » homogeneous and spherical compact grains, for which radiation pressure efficiency becomes lower when their sizes increase. In addition, we find that the outward mass flux of porous dust aggregates with monomer size of 0.1 μm is larger than that of compact grains by an order of magnitude at the disk radius of 1 AU, when their sizes are several microns. This implies that large compact grains like calcium-aluminum-rich inclusions are hardly transported to the outer region by stellar radiation pressure, whereas porous dust aggregates like chondritic-porous interplanetary dust particles are efficiently transported to the comet formation region. Crystalline silicates are possibly transported in porous dust aggregates by stellar radiation pressure from the inner hot region to the outer cold cometary region in the protosolar nebula.« less

A review on high-resolution CMOS delay lines: towards sub-picosecond jitter performance.

PubMed

Abdulrazzaq, Bilal I; Abdul Halin, Izhal; Kawahito, Shoji; Sidek, Roslina M; Shafie, Suhaidi; Yunus, Nurul Amziah Md

2016-01-01

A review on CMOS delay lines with a focus on the most frequently used techniques for high-resolution delay step is presented. The primary types, specifications, delay circuits, and operating principles are presented. The delay circuits reported in this paper are used for delaying digital inputs and clock signals. The most common analog and digitally-controlled delay elements topologies are presented, focusing on the main delay-tuning strategies. IC variables, namely, process, supply voltage, temperature, and noise sources that affect delay resolution through timing jitter are discussed. The design specifications of these delay elements are also discussed and compared for the common delay line circuits. As a result, the main findings of this paper are highlighting and discussing the followings: the most efficient high-resolution delay line techniques, the trade-off challenge found between CMOS delay lines designed using either analog or digitally-controlled delay elements, the trade-off challenge between delay resolution and delay range and the proposed solutions for this challenge, and how CMOS technology scaling can affect the performance of CMOS delay lines. Moreover, the current trends and efforts used in order to generate output delayed signal with low jitter in the sub-picosecond range are presented.

Currents through Hv1 channels deplete protons in their vicinity.

PubMed

De-la-Rosa, Víctor; Suárez-Delgado, Esteban; Rangel-Yescas, Gisela E; Islas, León D

2016-02-01

Proton channels have evolved to provide a pH regulatory mechanism, affording the extrusion of protons from the cytoplasm at all membrane potentials. Previous evidence has suggested that channel-mediated acid extrusion could significantly change the local concentration of protons in the vicinity of the channel. In this work, we directly measure the proton depletion caused by activation of Hv1 proton channels using patch-clamp fluorometry recordings from channels labeled with the Venus fluorescent protein at intracellular domains. The fluorescence of the Venus protein is very sensitive to pH, thus behaving as a genetically encoded sensor of local pH. Eliciting outward proton currents increases the fluorescence intensity of Venus. This dequenching is related to the magnitude of the current and not to channel gating and is dependent on the pH gradient. Our results provide direct evidence of local proton depletion caused by flux through the proton-selective channel. © 2016 De-la-Rosa et al.

Ca2+ ion permeability properties of (R,S) alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors in isolated interneurons from the olfactory bulb of the rat.

PubMed

Jardemark, K; Nilsson, M; Muyderman, H; Jacobson, I

1997-02-01

The aim of the study was to investigate the divalent cation permeability of native alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) receptors expressed in interneurons of the olfactory bulb. Kainic acid (KA) was used as agonist to activate AMPA-receptor-mediated currents, which were recorded with the use of the patch-clamp technique. In interneurons acutely isolated from the olfactory bulb, the current responses to KA showed linear/outwardly rectifying current-voltage (I-V) relationships with a positive average reversal potential of +7 mV in normal external medium (1 mM Ca2+, 1 mM Mg2+). Raising the external Ca2+ concentration to 10 mM suppressed the amplitude, whereas omission of Ca2+ enhanced the amplitude of the current. Spectral analysis of the increase in current variance produced by KA indicated that the decreased amplitude observed in 10 mM Ca2+ was accompanied by a reduction in the apparent single-channel conductance. Raising the concentration of Mg2+ from 1 to 10 mM had a weak depressant effect on the KA-evoked current amplitude. No shift in the reversal potential was observed when the concentration of Ca2+ or Mg2+ was changed from 1 to 10 mM. Increasing the external medium concentration of Ca2+ to 60 mM not only further depressed the amplitudes of the KA-evoked currents but also gave a pronounced leftward shift in the average reversal potential to -32 +/- 9 (SE) mV (N = 7). For neurons in primary culture, current responses to KA also showed linear/outwardly rectifying I-V relationships with a positive average reversal potential in normal external medium. Substituting N-methylglucamine for Na+ and increasing the Ca2+ concentration to 10 mM gave a leftward shift in the average reversal potential from +9 +/- 3 mV to -47 +/- 4 mV (N = 11) and caused a marked reduction in the amplitude of the KA-evoked currents at negative potentials. The permeability properties of the studied AMPA receptors were well predicted by the Eyring rate model (symmetrical, 2 barriers, 1 site). The model gave a pCa2+/pK+ permeability ratio of 0.06 for acutely isolated interneurons and 0.14 for interneurons in primary culture. The constant field theory, which failed to successfully reproduce all the experimental data, gave corresponding low permeability ratios of 0.18 and 0.40 for acutely isolated cells and cells in primary culture, respectively. Thus it is concluded that interneurons in the olfactory bulb mainly express AMPA receptors with low permeability to Ca2+ ions.

The synchronization of asymmetric-structured electric coupling neuronal system

NASA Astrophysics Data System (ADS)

Wang, Guanping; Jin, Wuyin; Liu, Hao; Sun, Wei

2018-02-01

Based on the Hindmarsh-Rose (HR) model, the synchronization dynamics of asymmetric-structured electric coupling two neuronal system is investigated in this paper. It is discovered that when the time-delay scope and coupling strength for the synchronization are correlated positively under unequal time delay, the time-delay difference does not make a clear distinction between the two individual inter-spike intervals (ISI) bifurcation diagrams of the two coupled neurons. Therefore, the superficial difference of the system synchronization dynamics is not obvious for the unequal time-delay feedback. In the asymmetrical current incentives under asymmetric electric coupled system, the two neurons can only be almost completely synchronized in specific area of the interval which end-pointed with two discharge modes for a single neuron under different stimuli currents before coupling, but the intervention of time-delay feedback, together with the change of the coupling strength, can make the coupled system not only almost completely synchronized within anywhere in the front area, but also outside of it.

For whom the bell tolls: experimentally-manipulated disgust and embarrassment may cause anticipated sexual healthcare avoidance among some people.

PubMed

McCambridge, Sarah A; Consedine, Nathan S

2014-04-01

This study was designed to experimentally determine whether disgust and embarrassment predict anticipated delay and avoidance in sexual healthcare decision-making and for whom. In the study, 90 participants, aged 18-30, completed web-based questionnaires assessing demographics, current health, and past health behaviors before being gender block randomized to conditions in which disgust, embarrassment, or control (no emotion) were induced. Participants completed health decision-making vignettes covering the disgusting and embarrassing aspects of sexual healthcare. Factorial ANOVAs showed that although there were some complexities in the manipulation, disgust and embarrassment predicted greater anticipated delay and avoidance of elicitors, but only among specific groups. Embarrassment predicted anticipated help-seeking delays for embarrassment elicitors (i.e. sexual history assessment and physical examination), while disgust predicted anticipated help-seeking delays involving disgust elicitors (i.e. collecting genital discharge). However, these effects were moderated, with embarrassment only predicting anticipated delays among individuals reporting multiple sexual partners and disgust predicting anticipated delays and avoidance among persons reporting poorer subjective health. In sum, the current report provides among the first empirical demonstrations that emotions such as embarrassment and disgust may be causally implicated in anticipated delays and avoidance in sexual healthcare. Emotion frameworks may be usefully incorporated into clinical and public health efforts to reduce sexual healthcare delays and avoidance.

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.

Intensity coding in electric hearing: Effects of electrode configurations and stimulation waveforms

PubMed Central

Chua, Tiffany Elise H.; Bachman, Mark; Zeng, Fan-Gang

2011-01-01

Objectives Current cochlear implants typically stimulate the auditory nerve with biphasic pulses and monopolar electrode configurations. Tripolar stimulation can increase spatial selectivity and potentially improve place pitch related perception, but requires higher current levels to elicit the same loudness as monopolar stimulation. The present study combined delayed pseudomonophonasic pulses, which produce lower thresholds, with tripolar stimulation in an attempt to solve the power-performance tradeoff problem. Design The present study systematically measured thresholds, dynamic range, loudness growth, and intensity discrimination using either biphasic or delayed pseudomonophonasic pulses under both monopolar and tripolar stimulation. Participants were 5 Clarion cochlear implant users. For each subject, data from apical, middle and basal electrode positions were collected when possible. Results Compared with biphasic pulses, delayed pseudomonophonasic pulses increased the dynamic range by lowering thresholds while maintaining comparable maximum allowable levels under both electrode configurations. However, delayed pseudomonophonasic pulses did not change the shape of loudness growth function and actually increased intensity discrimination limens, especially at lower current levels. Conclusions The present results indicate that delayed pseudomonophonasic pulses coupled with tripolar stimulation cannot provide significant power savings, nor can it increase the functional dynamic range. Whether this combined stimulation could improve functional spectral resolution remains to be seen. PMID:21610498

A unified theory of stable auroral red arc formation at the plasmapause

NASA Technical Reports Server (NTRS)

Cornwall, J. M.; Coroniti, F. V.; Thorne, R. M.

1970-01-01

A theory is proposed that SAR-arcs are generated at the plasmapause as a consequence of the turbulent dissipation of ring current energy. During the recovery phase of a geomagnetic storm, the plasmapause expands outward into the symmetric ring current. When the cold plasma densities reach about 100/cu cm, ring current protons become unstable and generate intense ion cyclotron wave turbulence in a narrow region 1/2 earth radius wide (just inside the plasmapause). Approximately one-half of the ring current energy is dissipated into wave turbulence which in turn is absorbed through a Landau resonant interaction with plasma spheric electrons. The combined thermal heat flux to the ionosphere due to Landau absorption of the wave energy and proton-electron Coulomb dissipation is sufficient to drive SAR-arcs at the observed intensities. It is predicted that the arcs should be localized to a narrow latitudinal range just within the stormtime plasmapause. They should occur at all local times and persist for the 10 to 20 hour duration of the plasma-pause expansion.

Inhibition of human ether-a-go-go-related gene K+ channel and IKr of guinea pig cardiomyocytes by antipsychotic drug trifluoperazine.

PubMed

Choi, Se-Young; Koh, Young-Sang; Jo, Su-Hyun

2005-05-01

Trifluoperazine, a commonly used antipsychotic drug, has been known to induce QT prolongation and torsades de pointes, which can cause sudden death. We studied the effects of trifluoperazine on the human ether-a-go-go-related gene (HERG) channel expressed in Xenopus oocytes and on the delayed rectifier K(+) current of guinea pig cardiomyocytes. The application of trifluoperazine showed a dose-dependent decrease in current amplitudes at the end of voltage steps and tail currents of HERG. The IC(50) for a trifluoperazine block of HERG current progressively decreased according to depolarization: IC(50) values at -40, 0, and +40 mV were 21.6, 16.6, and 9.29 microM, respectively. The voltage dependence of the block could be fitted with a monoexponential function, and the fractional electrical distance was estimated to be delta = 0.65. The block of HERG by trifluoperazine was use-dependent, exhibiting more rapid onset and greater steady-state block at higher frequencies of activation; there was partial relief of the block with decreasing frequency. In guinea pig ventricular myocytes, bath applications of 0.5 and 2 microM trifluoperazine at 36 degrees C blocked the rapidly activating delayed rectifier K(+) current by 32.4 and 72.9%, respectively; however, the same concentrations of trifluoperazine failed to significantly block the slowly activating delayed rectifier K(+) current. Our findings suggest the arrhythmogenic side effect of trifluoperazine is caused by a blockade of HERG and the rapid component of the delayed rectifier K(+) current rather than by the blockade of the slow component.

Chaos control by electric current in an enzymatic reaction.

PubMed

Lekebusch, A; Förster, A; Schneider, F W

1996-09-01

We apply the continuous delayed feedback method of Pyragas to control chaos in the enzymatic Peroxidase-Oxidase (PO) reaction, using the electric current as the control parameter. At each data point in the time series, a time delayed feedback function applies a small amplitude perturbation to inert platinum electrodes, which causes redox processes on the surface of the electrodes. These perturbations are calculated as the difference between the previous (time delayed) signal and the actual signal. Unstable periodic P1, 1(1), and 1(2) orbits (UPOs) were stabilized in the CSTR (continuous stirred tank reactor) experiments. The stabilization is demonstrated by at least three conditions: A minimum in the experimental dispersion function, the equality of the delay time with the period of the stabilized attractor and the embedment of the stabilized periodic attractor in the chaotic attractor.

Properties of voltage-activated Na+ and K+ currents in mouse hippocampal glial cells in situ and after acute isolation from tissue slices.

PubMed

Steinhäuser, C; Kressin, K; Kuprijanova, E; Weber, M; Seifert, G

1994-10-01

In the present study, we were interested in a quantitative analysis of voltage-activated channels in a subpopulation of hippocampal glial cells, termed "complex" cells. The patch-clamp technique in the whole-cell mode was applied to identified cells in situ and to glial cells acutely isolated from tissue slices. The outward current was composed of two components: a sustained and a transient current. The transient K+ channel had electrophysiological and pharmacological properties resembling those of the channel through which the A-currents pass. In addition, this glial A-type current possessed a significant Ca2+ dependence. The current parameters determined in situ or in isolated cells corresponded well. Due to space clamp problems in situ, properties of voltage-dependent Na+ currents were only analysed in suspended glial cells. The tetrodotoxin (TTX) sensitivity and the stationary and kinetic characteristics of this current were similar to corresponding properties of hippocampal neurons. These quantitative data demonstrate that at an early postnatal stage of central nervous system maturation, glial cells in situ express a complex pattern of voltage-gated ion channels. The results are compared to findings in other preparations and the possible consequences of transmitter-mediated channel modulation in glial cells are discussed.

Striate cortical contribution to the transcorneal electrically evoked response of the visual system.

PubMed

Shimazu, K; Miyake, Y; Fukatsu, Y; Watanabe, S

1996-01-01

Analyses of current-source-density (CSD) and multiple unit activity (MUA) in area 17 of the cat were performed to determine the sources of the cortical transcorneal electrically evoked response. Cortical field potential, CSD and MUA profiles were obtained with multi-electrodes. CSD findings include: current sinks (inward cell membrane current) within 20 ms latency, in layers 4 and 6 of the striate cortex; current sinks corresponding to N3 (negative component of the EER; latency, 35 ms) in layer 4 and lower layer 3 with current sources (outward cell membrane current) for N3 in the supragranular layers; current sinks with latency over 40 ms in the supragranular layers. In the layers 4 and 6, simultaneous MUA was seen. When the stimulus frequency was increased or with dual stimulation, the N3 current sinks were decreased. This indicates that N1 (latency, 9 ms) and N2 (latency, 20 ms) reflect near-field potentials in layers 4 and 6, generated by geniculocortical afferents, and that N3 is a post- and polysynaptic component. It is also suggested that dipoles composed of cell bodies and the apical dendrites of pyramidal cells of layer 3, generated by satellite cells in layer 4, play a major role in generating N3.

Characteristics of lightning flashes generating dancing sprites above thunderstorms

NASA Astrophysics Data System (ADS)

Soula, Serge; Mlynarczyk, Janusz; Füllekrug, Martin; Pineda, Nicolau; Georgis, Jean-François; van der Velde, Oscar; Montanyà, Joan; Fabro, Ferran

2017-04-01

During the night of October 29-30, 2013, a low-light video camera at Pic du Midi (2877 m) in the French Pyrénées, recorded TLEs above a very active storm over the Mediterranean Sea. The minimum cloud top temperature reached -73˚ C at ˜1600 UTC while its cloud to ground (CG) flash rate reached ˜30 fl min-1. Some sprite events with long duration are classified as dancing sprites. We analyze in detail the temporal evolution and estimated location of sprite elements for two cases of these events. They consist in series of sprite sequences with a duration that exceeds 1 second. By associating the cloud structure, the lightning activity, the electric field radiated in a broad range of low frequencies and the current moment waveform of the lightning strokes, some findings are highlighted: (i) In each series, successive sprite sequences reflect the occurrence time and location of individual positive lightning strokes across the stratiform region. (ii) The longer time-delayed (> 20 ms) sprite elements correspond to the lower impulsive charge moment changes (iCMC) of the parent stroke (< 200 C km) and they are shifted few tens of kilometres from their SP+CG stroke. However, both short and long time-delayed sprite elements also occur after strokes that produce a large iCMC and that are followed by a continuing current. (iii) The long time-delayed sprite elements produced during the continuing current correspond to surges in the current moment waveform. They occur sometimes at an altitude apparently lower than the previous short time-delayed sprite elements, possibly because of the lowered altitude of the ionosphere potential. (iv) The largest and brightest sprite elements produce significant current signatures, visible when their delay is not too short (˜3-5 ms).

Delay in micro-discharges appearance during PEO of Al: Evidence of a mechanism of charge accumulation at the electrolyte/oxide interface

NASA Astrophysics Data System (ADS)

Martin, J.; Nominé, A.; Brochard, F.; Briançon, J.-L.; Noël, C.; Belmonte, T.; Czerwiec, T.; Henrion, G.

2017-07-01

PEO was conducted on Al by applying a pulsed bipolar current. The role of the cathodic polarization on the appearance of micro-discharges (MDs) and on the subsequent formation of the PEO oxide layers is investigated. Various ratios of the charge quantity RCQ = Qp/Qn (defined as the anodic Qp to cathodic Qn charge quantity ratio over one current pulse period) in the range [0.5; 6.0] were selected by changing the waveform parameters of the cathodic current while keeping the waveform of the anodic current unchanged. Results show that the appearance of MDs is delayed with respect to the rising edge of the anodic current; this delay strongly depends on both the processing time and the applied cathodic charge quantity. It is also evidenced that shorter delays promoted by high RCQ values (RCQ > 1) are associated with stronger MDs (large size and long life) that have detrimental effects on the formed PEO oxide layers. Thicker and the more compact oxide layer morphology is achieved with the intermediate RCQ value (RCQ = 0.9) for which the delay of the MDs appearance is high and the MDs softer. Low RCQ (RCQ < 0.9) results in an earlier extinction of the MDs as the process goes on, which leads to poorly oxidized metal. A mechanism of charge accumulation taking place at the oxide/electrolyte interface and arising before the occurrence of dielectric breakdown is proposed to explain the ignition of MDs during pulsed bipolar PEO of aluminium. A close examination of the voltage-time response which can be adequately simulated with an equivalent RC circuit evidences the capacitive behaviour of the oxide layer and therefore confirms this proposed mechanism of charge accumulation.

The delay period as an opportunity to think about future intentions: Effects of delay length and delay task difficulty on young adult's prospective memory performance.

PubMed

Mahy, Caitlin E V; Schnitzspahn, Katharina; Hering, Alexandra; Pagobo, Jacqueline; Kliegel, Matthias

2018-05-01

The current study examined the impact of length and difficulty of the delay task on young adult's event-based prospective memory (PM). Participants engaged in either a short (2.5 min) or a long (15 min) delay that was filled with either a simple item categorization task or a difficult cognitive task. They also completed a questionnaire on whether they thought about the PM intention during the delay period and how often they thought about it. Results revealed that participants' PM was better after a difficult delay task compared to an easy delay task. Participants thought about the PM intention more often during the difficult delay task than during the easy delay task. PM performance was positively related to participants' reports of how many times they thought about their intentions. The important role of delay task difficulty in allowing or preventing individuals from refreshing their future intentions is discussed.

Control of Electromagnetic Scattering by Antenna Impedance Loading

DTIC Science & Technology

1974-07-01

system and whose profile in a plane perpendicular to the z axis is the closed curve c. Let n be an outward unit vector to c and let t be a unit... vector in the tangential direction, such that t, n and z form a right-hand system. Then, on the surface, the impedance boundary con- dition is...and is given by J Mn x z)H* where n is the unit outward normal vector to the surface. Using the GTD solution for the total magnetic field, the

Low-temperature Ignition-delay Characteristics of Several Rocket Fuels with Mixed Acid in Modified Open-cup-type Apparatus

NASA Technical Reports Server (NTRS)

Miller, Riley O

1950-01-01

Summaries of low-temperature self-ignition data of various rocket fuels with mixed acid (nitric plus sulfuric) are presented. Several fuels are shown to have shorter ignition-delay intervals and less variation in delay intervals at moderate and sub-zero temperatures than crude N-ethylaniline (monoethylaniline),a rocket fuel in current use.

Ultra high performance connectors for power transmission applications

DOEpatents

Wang, Jy-An; Ren, Fei; Lee, Dominic F; Jiang, Hao

2014-03-04

Disclosed are several examples of an apparatus for connecting the free ends of two electrical power transmission lines having conductor strands disposed around a central, reinforcing core. The examples include an inner sleeve having a body defining an inner bore passing through an axially-extending, central axis, an outer rim surface disposed radially outward from the central bore, and one or more axially-extending grooves penetrating the body at the outer rim surface. Also included is an outer splice having a tubular shaped body with a bore passing coaxially through the central axis, the bore defining an inner rim surface for accepting the inner sleeve. The inner bore of the inner sleeve accepts the reinforcement cores of the two conductors, and the grooves accept the conductor strands in an overlapping configuration so that a majority of the electrical current flows between the overlapped conductor strands when the conductors are transmitting electrical current.

Magnetic field and electric current structure in the chromosphere

NASA Technical Reports Server (NTRS)

Dravins, D.

1974-01-01

The three-dimensional vector magnetic field structure in the chromosphere above an active region is deduced by using high-resolution H-alpha filtergrams together with a simultaneous digital magnetogram. An analog model of the field is made with 400 metal wires representing field lines that outline the H-alpha structure. The height extent of the field is determined from vertical field-gradient observations around sunspots, from observed fibril heights, and from an assumption that the sources of the field are largely local. The computed electric currents (typically 10 mA/sq m) are found to flow in patterns not similar to observed features and not parallel to magnetic fields. Force structures correspond to observed solar features; the dynamics to be expected include: downward motion in bipolar areas in the lower chromosphere, an outflow of the outer chromosphere into the corona with radially outward flow above bipolar plage regions, and motion of arch filament systems.

Voltage-clamp study of the activation currents and fast block to polyspermy in the egg of Xenopus laevis.

PubMed

Glahn, David; Nuccitelli, Richard

2003-04-01

Voltage-clamped mature, jelly-intact Xenopus eggs were used to carefully examine the ionic currents crossing the plasma membrane before, during, and after fertilization. The bulk of the fertilization current was transient, of large amplitude, and reversed at the predicted Cl- reversal potential. However, the large amplitude fertilization current was preceded by a small, step-like increase in holding current. This small increase in holding current is referred to in this paper as Ion to acknowledge its qualitative similarity to the Ion current previously described in the sea urchin. It was observed in both fertilized and artificially activated eggs, and was found to be unaffected by 10 mm tetra-ethyl ammonium (TEA), a concentration found to block K+ currents in Rana pipiens. Current-voltage relationships are presented for the large fertilization potential, and show that the fertilization currents have a marked outward rectification and are voltage sensitive. These properties are in contrast to the total lack of rectification and slight voltage sensitivity seen before or after the fertilization currents. The time required for sperm to fertilize the egg was found to be voltage dependent with a relatively more depolarized voltage requiring a longer time for fertilization to occur. The percentage of eggs blocked with varying potential levels was determined and this information was fitted to a modified Boltzmann equation having a midpoint of -9 mV.

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

Dayside ionospheric convection changes in response to long-period interplanetary magnetic field oscillations - Determination of the ionospheric phase velocity

NASA Technical Reports Server (NTRS)

Saunders, M. A.; Freeman, M. P.; Southwood, D. J.; Cowley, S. W.; Lockwood, M.; Samson, J. C.; Farrugia, C. J.; Hughes, T. J.

1992-01-01

Ground magnetic field perturbations recorded by the CANOPUS magnetometer network in the 7 to 13 MLT sector are used to examine how reconfigurations of the dayside polar ionospheric flow take place in response to north-south changes of the IMF. During the 6-h interval in question, IMF Bz oscillates between +/- 7 nT with about a 1-h period. Corresponding variations in the ground magnetic disturbance are observed which we infer are due to changes in ionospheric flow. Cross correlation of the data obtained from two ground stations at 73.5 deg magnetic latitude, but separated by about 2 hours in MLT, shows that changes in the flow are initiated in the prenoon sector (about 10 MLT) and then spread outward toward dawn and dusk with a phase speed of about 5 km/s over the longitude range about 8 to 12 MLT, slowing to about 2 km/s outside this range. Cross correlating the data from these ground stations with IMP 8 IMF Bz records produces a MLT variation in the ground response delay relative to the IMF which is compatible with these deduced phase speeds.

Longest delayed hemothorax reported after blunt chest injury.

PubMed

Yap, Darren; Ng, Miane; Chaudhury, Madhu; Mbakada, Nik

2018-01-01

Blunt chest injury is a common presentation to the emergency department. However, a delayed hemothorax after blunt trauma is rare; current literature reports a delay of up to 30days. We present a case of 44-day delay in hemothorax which has not been previously reported in current literature. A 52-year-old Caucasian male first presented to the emergency department complaining of persistent right sided chest pain 2weeks after having slipped on a wet surface at home. His initial chest X-ray showed fractures of the right 7th and 8th ribs without a hemothorax or pneumothorax. He returned 30days after the initial consultation (44days post-trauma) having increasing shortness of breath. A chest X-ray this time revealed a large right hemothorax and 1850ml of blood drained from his chest. There was a complete resolution of the hemothorax within 48h and the patient was discharged after a 6-week follow-up with the chest physicians. Delayed hemothorax after blunt trauma is a rare clinical occurrence but associated with significant morbidity and mortality. The management of delayed hemothorax includes draining the hemothorax and controlling the bleeding. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Emergency physicians should be vigilant and weary that hemothorax could be a possibility after a chest injury despite a delay in presentation. A knowledge of delayed hemothorax will prompt physicians in providing important advice, warning signs and information to patients after a chest injury to avoid a delay in seeking medical attention. Copyright © 2017 Elsevier Inc. All rights reserved.

Modeling Slab-Slab Interactions: Dynamics of Outward Dipping Double-Sided Subduction Systems

NASA Astrophysics Data System (ADS)

Király, Ágnes; Holt, Adam F.; Funiciello, Francesca; Faccenna, Claudio; Capitanio, Fabio A.

2018-03-01

Slab-slab interaction is a characteristic feature of tectonically complex areas. Outward dipping double-sided subduction is one of these complex cases, which has several examples on Earth, most notably the Molucca Sea and Adriatic Sea. This study focuses on developing a framework for linking plate kinematics and slab interactions in an outward dipping subduction geometry. We used analog and numerical models to better understand the underlying subduction dynamics. Compared to a single subduction model, double-sided subduction exhibits more time-dependent and vigorous toroidal flow cells that are elongated (i.e., not circular). Because both the Molucca and Adriatic Sea exhibit an asymmetric subduction configuration, we also examine the role that asymmetry plays in the dynamics of outward dipping double-sided subduction. We introduce asymmetry in two ways; with variable initial depths for the two slabs ("geometric" asymmetry), and with variable buoyancy within the subducting plate ("mechanical" asymmetry). Relative to the symmetric case, we probe how asymmetry affects the overall slab kinematics, whether asymmetric behavior intensifies or equilibrates as subduction proceeds. While initial geometric asymmetry disappears once the slabs are anchored to the 660 km discontinuity, the mechanical asymmetry can cause more permanent differences between the two subduction zones. In the most extreme case, the partly continental slab stops subducting due to the unequal slab pull force. The results show that the slab-slab interaction is most effective when the two trenches are closer than 10-8 cm in the laboratory, which is 600-480 km when scaled to the Earth.

Molecular Dynamics Simulations of the Human Glucose Transporter GLUT1

PubMed Central

Park, Min-Sun

2015-01-01

Glucose transporters (GLUTs) provide a pathway for glucose transport across membranes. Human GLUTs are implicated in devastating diseases such as heart disease, hyper- and hypo-glycemia, type 2 diabetes and caner. The human GLUT1 has been recently crystalized in the inward-facing open conformation. However, there is no other structural information for other conformations. The X-ray structures of E. coli Xylose permease (XylE), a glucose transporter homolog, are available in multiple conformations with and without the substrates D-xylose and D-glucose. XylE has high sequence homology to human GLUT1 and key residues in the sugar-binding pocket are conserved. Here we construct a homology model for human GLUT1 based on the available XylE crystal structure in the partially occluded outward-facing conformation. A long unbiased all atom molecular dynamics simulation starting from the model can capture a new fully opened outward-facing conformation. Our investigation of molecular interactions at the interface between the transmembrane (TM) domains and the intracellular helices (ICH) domain in the outward- and inward-facing conformation supports that the ICH domain likely stabilizes the outward-facing conformation in GLUT1. Furthermore, inducing a conformational transition, our simulations manifest a global asymmetric rocker switch motion and detailed molecular interactions between the substrate and residues through the water-filled selective pore along a pathway from the extracellular to the intracellular side. The results presented here are consistent with previously published biochemical, mutagenesis and functional studies. Together, this study shed light on the structure and functional relationships of GLUT1 in multiple conformational states. PMID:25919356

Water reservoir maintained by cell growth fuels the spreading of a bacterial swarm

PubMed Central

Wu, Yilin; Berg, Howard C.

2012-01-01

Flagellated bacteria can swim across moist surfaces within a thin layer of fluid, a means for surface colonization known as swarming. This fluid spreads with the swarm, but how it does so is unclear. We used micron-sized air bubbles to study the motion of this fluid within swarms of Escherichia coli. The bubbles moved diffusively, with drift. Bubbles starting at the swarm edge drifted inward for the first 5 s and then moved outward. Bubbles starting 30 μm from the swarm edge moved inward for the first 20 s, wandered around in place for the next 40 s, and then moved outward. Bubbles starting at 200 or 300 μm from the edge moved outward or wandered around in place, respectively. So the general trend was inward near the outer edge of the swarm and outward farther inside, with flows converging on a region about 100 μm from the swarm edge. We measured cellular metabolic activities with cells expressing a short-lived GFP and cell densities with cells labeled with a membrane fluorescent dye. The fluorescence plots were similar, with peaks about 80 μm from the swarm edge and slopes that mimicked the particle drift rates. These plots suggest that net fluid flow is driven by cell growth. Fluid depth is largest in the multilayered region between approximately 30 and 200 μm from the swarm edge, where fluid agitation is more vigorous. This water reservoir travels with the swarm, fueling its spreading. Intercellular communication is not required; cells need only grow. PMID:22371567

Water reservoir maintained by cell growth fuels the spreading of a bacterial swarm.

PubMed

Wu, Yilin; Berg, Howard C

2012-03-13

Flagellated bacteria can swim across moist surfaces within a thin layer of fluid, a means for surface colonization known as swarming. This fluid spreads with the swarm, but how it does so is unclear. We used micron-sized air bubbles to study the motion of this fluid within swarms of Escherichia coli. The bubbles moved diffusively, with drift. Bubbles starting at the swarm edge drifted inward for the first 5 s and then moved outward. Bubbles starting 30 μm from the swarm edge moved inward for the first 20 s, wandered around in place for the next 40 s, and then moved outward. Bubbles starting at 200 or 300 μm from the edge moved outward or wandered around in place, respectively. So the general trend was inward near the outer edge of the swarm and outward farther inside, with flows converging on a region about 100 μm from the swarm edge. We measured cellular metabolic activities with cells expressing a short-lived GFP and cell densities with cells labeled with a membrane fluorescent dye. The fluorescence plots were similar, with peaks about 80 μm from the swarm edge and slopes that mimicked the particle drift rates. These plots suggest that net fluid flow is driven by cell growth. Fluid depth is largest in the multilayered region between approximately 30 and 200 μm from the swarm edge, where fluid agitation is more vigorous. This water reservoir travels with the swarm, fueling its spreading. Intercellular communication is not required; cells need only grow.

Hot super-Earths and giant planet cores from different migration histories

NASA Astrophysics Data System (ADS)

Cossou, Christophe; Raymond, Sean N.; Hersant, Franck; Pierens, Arnaud

2014-09-01

Planetary embryos embedded in gaseous protoplanetary disks undergo Type I orbital migration. Migration can be inward or outward depending on the local disk properties but, in general, only planets more massive than several M⊕ can migrate outward. Here we propose that an embryo's migration history determines whether it becomes a hot super-Earth or the core of a giant planet. Systems of hot super-Earths (or mini-Neptunes) form when embryos migrate inward and pile up at the inner edge of the disk. Giant planet cores form when inward-migrating embryos become massive enough to switch direction and migrate outward. We present simulations of this process using a modified N-body code, starting from a swarm of planetary embryos. Systems of hot super-Earths form in resonant chains with the innermost planet at or interior to the disk inner edge. Resonant chains are disrupted by late dynamical instabilities triggered by the dispersal of the gaseous disk. Giant planet cores migrate outward toward zero-torque zones, which move inward and eventually disappear as the disk disperses. Giant planet cores migrate inward with these zones and are stranded at ~1-5 AU. Our model reproduces several properties of the observed extra-solar planet populations. The frequency of giant planet cores increases strongly when the mass in solids is increased, consistent with the observed giant exoplanet - stellar metallicity correlation. The frequency of hot super-Earths is not a function of stellar metallicity, also in agreement with observations. Our simulations can reproduce the broad characteristics of the observed super-Earth population.

Out of Africa: modern human origins special feature: explaining worldwide patterns of human genetic variation using a coalescent-based serial founder model of migration outward from Africa.

PubMed

DeGiorgio, Michael; Jakobsson, Mattias; Rosenberg, Noah A

2009-09-22

Studies of worldwide human variation have discovered three trends in summary statistics as a function of increasing geographic distance from East Africa: a decrease in heterozygosity, an increase in linkage disequilibrium (LD), and a decrease in the slope of the ancestral allele frequency spectrum. Forward simulations of unlinked loci have shown that the decline in heterozygosity can be described by a serial founder model, in which populations migrate outward from Africa through a process where each of a series of populations is formed from a subset of the previous population in the outward expansion. Here, we extend this approach by developing a retrospective coalescent-based serial founder model that incorporates linked loci. Our model both recovers the observed decline in heterozygosity with increasing distance from Africa and produces the patterns observed in LD and the ancestral allele frequency spectrum. Surprisingly, although migration between neighboring populations and limited admixture between modern and archaic humans can be accommodated in the model while continuing to explain the three trends, a competing model in which a wave of outward modern human migration expands into a series of preexisting archaic populations produces nearly opposite patterns to those observed in the data. We conclude by developing a simpler model to illustrate that the feature that permits the serial founder model but not the archaic persistence model to explain the three trends observed with increasing distance from Africa is its incorporation of a cumulative effect of genetic drift as humans colonized the world.

[Lead compound optimization strategy(5) – reducing the hERG cardiac toxicity in drug development].

PubMed

Zhou, Sheng-bin; Wang, Jiang; Liu, Hong

2016-10-01

The potassium channel encoded by the human ether-a-go-go related gene(hERG) plays a very important role in the physiological and pathological processes in human. hERG potassium channel determines the outward currents which facilitate the repolarization of the myocardial cells. Some drugs were withdrawn from the market for the serious side effect of long QT interval and arrhythmia due to blockade of hERG channel. The strategies for lead compound optimization are to reduce inhibitory activity of hERG potassium channel and decrease cardiac toxicity. These methods include reduction of lipophilicity and basicity of amines, introduction of hydroxyl and acidic groups, and restricting conformation.

Gating by Cyclic Gmp and Voltage in the α Subunit of the Cyclic Gmp–Gated Channel from Rod Photoreceptors

PubMed Central

Benndorf, Klaus; Koopmann, Rolf; Eismann, Elisabeth; Kaupp, U. Benjamin

1999-01-01

Gating by cGMP and voltage of the α subunit of the cGMP-gated channel from rod photoreceptor was examined with a patch-clamp technique. The channels were expressed in Xenopus oocytes. At low [cGMP] (<20 μM), the current displayed strong outward rectification. At low and high (700 μM) [cGMP], the channel activity was dominated by only one conductance level. Therefore, the outward rectification at low [cGMP] results solely from an increase in the open probability, P o. Kinetic analysis of single-channel openings revealed two exponential distributions. At low [cGMP], the larger P o at positive voltages with respect to negative voltages is caused by an increased frequency of openings in both components of the open-time distribution. In macroscopic currents, depolarizing voltage steps, starting from −100 mV, generated a time-dependent current that increased with the step size (activation). At low [cGMP] (20 μM), the degree of activation was large and the time course was slow, whereas at saturating [cGMP] (7 mM) the respective changes were small and fast. The dose–response relation at −100 mV was shifted to the right and saturated at significantly lower P o values with respect to that at +100 mV (0.77 vs. 0.96). P o was determined as function of the [cGMP] (at +100 and −100 mV) and voltage (at 20, 70, and 700 μM, and 7 mM cGMP). Both relations could be fitted with an allosteric state model consisting of four independent cGMP-binding reactions and one voltage-dependent allosteric opening reaction. At saturating [cGMP] (7 mM), the activation time course was monoexponential, which allowed us to determine the individual rate constants for the allosteric reaction. For the rapid rate constants of cGMP binding and unbinding, lower limits are determined. It is concluded that an allosteric model consisting of four independent cGMP-binding reactions and one voltage-dependent allosteric reaction, describes the cGMP- and voltage-dependent gating of cGMP-gated channels adequately. PMID:10498668

Unique Cardiac Purkinje Fiber Transient Outward Current β-Subunit Composition

PubMed Central

Xiao, Ling; Koopmann, Tamara T.; Ördög, Balázs; Postema, Pieter G.; Verkerk, Arie O.; Iyer, Vivek; Sampson, Kevin J.; Boink, Gerard J.J.; Mamarbachi, Maya A.; Varro, Andras; Jordaens, Luc; Res, Jan; Kass, Robert S.; Wilde, Arthur A.; Bezzina, C.R.; Nattel, Stanley

2015-01-01

Rationale A chromosomal haplotype producing cardiac overexpression of dipeptidyl peptidase-like protein-6 (DPP6) causes familial idiopathic ventricular fibrillation. The molecular basis of transient outward current (Ito) in Purkinje fibers (PFs) is poorly understood. We hypothesized that DPP6 contributes to PF Ito and that its overexpression might specifically alter PF Ito properties and repolarization. Objective To assess the potential role of DPP6 in PF Ito. Methods and Results Clinical data in 5 idiopathic ventricular fibrillation patients suggested arrhythmia origin in the PF-conducting system. PF and ventricular muscle Ito had similar density, but PF Ito differed from ventricular muscle in having tetraethylammonium sensitivity and slower recovery. DPP6 overexpression significantly increased, whereas DPP6 knockdown reduced, Ito density and tetraethylammonium sensitivity in canine PF but not in ventricular muscle cells. The K+-channel interacting β-subunit K+-channel interacting protein type-2, essential for normal expression of Ito in ventricular muscle, was weakly expressed in human PFs, whereas DPP6 and frequenin (neuronal calcium sensor-1) were enriched. Heterologous expression of Kv4.3 in Chinese hamster ovary cells produced small Ito; Ito amplitude was greatly enhanced by coexpression with K+-channel interacting protein type-2 or DPP6. Coexpression of DPP6 with Kv4.3 and K+-channel interacting protein type-2 failed to alter Ito compared with Kv4.3/K+-channel interacting protein type-2 alone, but DPP6 expression with Kv4.3 and neuronal calcium sensor-1 (to mimic PF Ito composition) greatly enhanced Ito compared with Kv4.3/neuronal calcium sensor-1 and recapitulated characteristic PF kinetic/pharmacological properties. A mathematical model of cardiac PF action potentials showed that Ito enhancement can greatly accelerate PF repolarization. Conclusions These results point to a previously unknown central role of DPP6 in PF Ito, with DPP6 gain of function selectively enhancing PF current, and suggest that a DPP6-mediated PF early-repolarization syndrome might be a novel molecular paradigm for some forms of idiopathic ventricular fibrillation. PMID:23532596

The Moderating Role of Dysfunctional Parent-Child Relationships on the Association Between Outward Anger Expression and Physical Health in Youth From Low-Income Families.

PubMed

Guenther, Kassie D; Van Dyk, Tori R; Kidwell, Katherine M; Nelson, Timothy D

2016-01-01

The purpose of this study is to examine the role of outward anger expression on physical health outcomes (number of illnesses in the past year, 2-year medical service utilization, and health-related quality of life) while also expanding on previous research by assessing the moderating effect of parent-child dysfunction. An ethnically diverse sample of 125 children, ages 8 to 11 years, was recruited from a family medicine practice serving a low-income population. High levels of outward anger expression were related to a greater number of illnesses, greater medical service utilization, and lower health-related quality of life. Additionally, worse parent-child dysfunction exacerbated this relationship for a number of illnesses and medical service utilization. Results suggest that health care providers should consider the influence of environmental and familial factors on the physical health of children with anger. Recommendations for identifying at-risk youth and improving anger expression as well as parent-child relationships are provided. Copyright © 2016 National Association of Pediatric Nurse Practitioners. Published by Elsevier Inc. All rights reserved.

Does the Alfvén wave wreck the large-scale magnetic cloud structure?

NASA Astrophysics Data System (ADS)

Raghav, Anil N.; Kule, Ankita

2018-06-01

Alfvén waves are primal and pervasive in space plasmas and significantly contributes to microscale fluctuations in the solar wind and some heliospheric processes. Here, we demonstrate the first observable distinct feature of Alfvén wave while propagating from magnetic cloud to trailing solar wind. The Walén test is used to confirm their presence in selected regions. The amplitude ratio of inward to outward Alfvén waves is employed to establish their flow direction. The dominant inward flow is observed in magnetic cloud whereas trailing solar wind shows the dominant outward flow of Alfvén waves. The observed reduction in Walén slope and correlation coefficient within magnetic cloud suggest (i) the simultaneous presence of an inward & outward Alfvén waves and/or (ii) a possibility of magnetic reconnection and/or (iii) development of thermal anisotropy and/or (iv) dissipation of Alfvénic fluctuations. The study implies that either the Alfvén waves dissipate in the magnetic cloud or its presence can lead to disruption of the magnetic cloud structure.

What's in and what's out in branding? A novel articulation effect for brand names

PubMed Central

Topolinski, Sascha; Zürn, Michael; Schneider, Iris K.

2015-01-01

The present approach exploits the biomechanical connection between articulation and ingestion-related mouth movements to introduce a novel psychological principle of brand name design. We constructed brand names for diverse products with consonantal stricture spots either from the front to the rear of the mouth, thus inwards (e.g., BODIKA), or from the rear to the front, thus outwards (e.g., KODIBA). These muscle dynamics resemble the oral kinematics during either ingestion (inwards), which feels positive, or expectoration (outwards), which feels negative. In 7 experiments (total N = 1261), participants liked products with inward names more than products with outward names (Experiment 1), reported higher purchase intentions (Experiment 2), and higher willingness-to-pay (Experiments 3a–3c, 4, 5), with the price gain amounting to 4–13% of the average estimated product value. These effects occurred across English and German language, under silent reading, for both edible and non-edible products, and even in the presence of a much stronger price determinant, namely fair-trade production (Experiment 5). PMID:26029136

The Role of Covert Retrieval in Working Memory Span Tasks: Evidence from Delayed Recall Tests

ERIC Educational Resources Information Center

McCabe, David P.

2008-01-01

The current study examined delayed recall of items that had been processed during simple and complex span tasks. Three experiments were reported showing that despite more items being recalled initially from a simple span task (i.e., word span) than a complex span task (i.e., operation span), on a delayed recall test more items were recalled that…

The Effects of Embedded Skill Instruction on the Acquisition of Target and Nontarget Skills in Preschoolers with Developmental Delays.

ERIC Educational Resources Information Center

Daugherty, Stefanie; Grisham-Brown, Jennifer; Hemmeter, Mary Louise

2001-01-01

In the current study, a constant time delay (CTD) procedure was embedded in classroom activities and routines to teach counting to three preschool children with speech and language delays. CTD was effective in teaching numbers to all three children. One child out of two also was able to acquire non-target information. (Contains references.) (CR)

Automated and manual patch clamp data of human induced pluripotent stem cell-derived dopaminergic neurons.

PubMed

Franz, Denise; Olsen, Hervør Lykke; Klink, Oliver; Gimsa, Jan

2017-04-25

Human induced pluripotent stem cells can be differentiated into dopaminergic neurons (Dopa.4U). Dopa.4U neurons expressed voltage-gated Na V and K V channels and showed neuron-like spontaneous electrical activity. In automated patch clamp measurements with suspended Dopa.4U neurons, delayed rectifier K + current (delayed K V ) and rapidly inactivating A-type K + current (fast K V ) were identified. Examination of the fast K V current with inhibitors yielded IC 50 values of 0.4 mM (4-aminopyridine) and 0.1 mM (tetraethylammonium). In manual patch clamp measurements with adherent Dopa.4U neurons, fast K V current could not be detected, while the delayed K V current showed an IC 50 of 2 mM for 4-aminopyridine. The Na V channels in adherent and suspended Dopa.4U neurons showed IC 50 values for tetrodotoxin of 27 and 2.9 nM, respectively. GABA-induced currents that could be observed in adherent Dopa.4U neurons could not be detected in suspended cells. Application of current pulses induced action potentials in approx. 70 % of the cells. Our results proved the feasibility of automated electrophysiological characterization of neuronal cells.

Climate change and decadal shifts in the phenology of larval fishes in the California Current ecosystem

PubMed Central

Asch, Rebecca G.

2015-01-01

Climate change has prompted an earlier arrival of spring in numerous ecosystems. It is uncertain whether such changes are occurring in Eastern Boundary Current Upwelling ecosystems, because these regions are subject to natural decadal climate variability, and regional climate models predict seasonal delays in upwelling. To answer this question, the phenology of 43 species of larval fishes was investigated between 1951 and 2008 off southern California. Ordination of the fish community showed earlier phenological progression in more recent years. Thirty-nine percent of seasonal peaks in larval abundance occurred earlier in the year, whereas 18% were delayed. The species whose phenology became earlier were characterized by an offshore, pelagic distribution, whereas species with delayed phenology were more likely to reside in coastal, demersal habitats. Phenological changes were more closely associated with a trend toward earlier warming of surface waters rather than decadal climate cycles, such as the Pacific Decadal Oscillation and North Pacific Gyre Oscillation. Species with long-term advances and delays in phenology reacted similarly to warming at the interannual time scale as demonstrated by responses to the El Niño Southern Oscillation. The trend toward earlier spawning was correlated with changes in sea surface temperature (SST) and mesozooplankton displacement volume, but not coastal upwelling. SST and upwelling were correlated with delays in fish phenology. For species with 20th century advances in phenology, future projections indicate that current trends will continue unabated. The fate of species with delayed phenology is less clear due to differences between Intergovernmental Panel on Climate Change models in projected upwelling trends. PMID:26159416

Device and circuit-level performance of carbon nanotube field-effect transistor with benchmarking against a nano-MOSFET.

PubMed

Tan, Michael Loong Peng; Lentaris, Georgios; Amaratunga Aj, Gehan

2012-08-19

The performance of a semiconducting carbon nanotube (CNT) is assessed and tabulated for parameters against those of a metal-oxide-semiconductor field-effect transistor (MOSFET). Both CNT and MOSFET models considered agree well with the trends in the available experimental data. The results obtained show that nanotubes can significantly reduce the drain-induced barrier lowering effect and subthreshold swing in silicon channel replacement while sustaining smaller channel area at higher current density. Performance metrics of both devices such as current drive strength, current on-off ratio (Ion/Ioff), energy-delay product, and power-delay product for logic gates, namely NAND and NOR, are presented. Design rules used for carbon nanotube field-effect transistors (CNTFETs) are compatible with the 45-nm MOSFET technology. The parasitics associated with interconnects are also incorporated in the model. Interconnects can affect the propagation delay in a CNTFET. Smaller length interconnects result in higher cutoff frequency.

Delayed fission of atomic nuclei (To the 50th anniversary of the discovery)

NASA Astrophysics Data System (ADS)

Skobelev, N. K.

2017-09-01

The history of the discovery of delayed nuclear fission is presented, and the retrospective of investigations into this phenomenon that were performed at various research centers worldwide is outlined. The results obtained by measuring basic delayed-fission features, including the fission probability, the total kinetic energy of fission fragments, and their mass distributions, are analyzed. Recommendations concerning further studies in various regions of nuclear map with the aim of searches for and investigation of atomic nuclei undergoing delayed fission are given. Lines of further research into features of delayed fission with the aim of solving current problems of fission physics are discussed.

Analyzing Impact Factors of Airport Taxiing Delay Based on Ads-B Data

NASA Astrophysics Data System (ADS)

Li, J.; Wang, X.; Xu, Y.; Li, Q.; He, C.; Li, Y.

2017-09-01

Identifying the factors that cause taxiing delay on airports is a prerequisite for optimizing aircraft taxiing schemes, and helps improve the efficiency of taxiing system. Few of current studies had quantified the potential influencing factors and further investigated their intrinsic relationship. In view of these problems, this paper uses ADS-B data to calculate taxiing delay time by restoring taxiing route and identifying key status points, and further analyzes the impact factors of airport taxiing delay by investigating the relationship between delay time and environmental data such as weather, wind, visibility etc. The case study in Guangzhou Baiyun Airport validates the effectiveness of the proposed method.

A New Method to Test the Einstein’s Weak Equivalence Principle

NASA Astrophysics Data System (ADS)

Yu, Hai; Xi, Shao-Qiang; Wang, Fa-Yin

2018-06-01

The Einstein’s weak equivalence principle (WEP) is one of the foundational assumptions of general relativity and some other gravity theories. In the theory of parametrized post-Newtonian (PPN), the difference between the PPN parameters γ of different particles or the same type of particle with different energies, Δγ, represents the violation of WEP. Current constraints on Δγ are derived from the observed time delay between correlated particles of astronomical sources. However, the observed time delay is contaminated by other effects, such as the time delays due to different particle emission times, the potential Lorentz invariance violation, and none-zero photon rest mass. Therefore, current constraints are only upper limits. Here, we propose a new method to test WEP based on the fact that the gravitational time delay is direction-dependent while others are not. This is the first method that can naturally correct other time-delay effects. Using the time-delay measurements of BASTE gamma-ray burst sample and the gravitational potential of local super galaxy cluster Laniakea, we find that the constraint on Δγ of different energy photons can be as low as 10‑14. In the future, if more gravitational wave events and fast radio bursts with much more precise time-delay measurements are observed, this method can give a reliable and tight constraint on WEP.

An active balance board system with real-time control of stiffness and time-delay to assess mechanisms of postural stability.

PubMed

Cruise, Denise R; Chagdes, James R; Liddy, Joshua J; Rietdyk, Shirley; Haddad, Jeffrey M; Zelaznik, Howard N; Raman, Arvind

2017-07-26

Increased time-delay in the neuromuscular system caused by neurological disorders, concussions, or advancing age is an important factor contributing to balance loss (Chagdes et al., 2013, 2016a,b). We present the design and fabrication of an active balance board system that allows for a systematic study of stiffness and time-delay induced instabilities in standing posture. Although current commercial balance boards allow for variable stiffness, they do not allow for manipulation of time-delay. Having two controllable parameters can more accurately determine the cause of balance deficiencies, and allows us to induce instabilities even in healthy populations. An inverted pendulum model of human posture on such an active balance board predicts that reduced board rotational stiffness destabilizes upright posture through board tipping, and limit cycle oscillations about the upright position emerge as feedback time-delay is increased. We validate these two mechanisms of instability on the designed balance board, showing that rotational stiffness and board time-delay induced the predicted postural instabilities in healthy, young adults. Although current commercial balance boards utilize control of rotational stiffness, real-time control of both stiffness and time-delay on an active balance board is a novel and innovative manipulation to reveal balance deficiencies and potentially improve individualized balance training by targeting multiple dimensions contributing to standing balance. Copyright © 2017 Elsevier Ltd. All rights reserved.

Inward rectifier potassium current (I K1) and Kir2 composition of the zebrafish (Danio rerio) heart.

PubMed

Hassinen, Minna; Haverinen, Jaakko; Hardy, Matt E; Shiels, Holly A; Vornanen, Matti

2015-12-01

Electrophysiological properties and molecular background of the zebrafish (Danio rerio) cardiac inward rectifier current (IK1) were examined. Ventricular myocytes of zebrafish have a robust (-6.7 ± 1.2 pA pF(-1) at -120 mV) strongly rectifying and Ba(2+)-sensitive (IC50 = 3.8 μM) IK1. Transcripts of six Kir2 channels (drKir2.1a, drKir2.1b, drKir2.2a, drKir2.2b, drKir2.3, and drKir2.4) were expressed in the zebrafish heart. drKir2.4 and drKir2.2a were the dominant isoforms in both the ventricle (92.9 ± 1.5 and 6.3 ± 1.5%) and the atrium (28.9 ± 2.9 and 64.7 ± 3.0%). The remaining four channels comprised together less than 1 and 7 % of the total transcripts in ventricle and atrium, respectively. The four main gene products (drKir2.1a, drKir2.2a, drKir2.2b, drKir2.4) were cloned, sequenced, and expressed in HEK cells for electrophysiological characterization. drKir2.1a was the most weakly rectifying (passed more outward current) and drKir2.2b the most strongly rectifying (passed less outward current) channel, whilst drKir2.2a and drKir2.4 were intermediate between the two. In regard to sensitivity to Ba(2+) block, drKir2.4 was the most sensitive (IC50 = 1.8 μM) and drKir2.1a the least sensitive channel (IC50 = 132 μM). These findings indicate that the Kir2 isoform composition of the zebrafish heart markedly differs from that of mammalian hearts. Furthermore orthologous Kir2 channels (Kir2.1 and Kir2.4) of zebrafish and mammals show striking differences in Ba(2+)-sensitivity. Structural and functional differences needs to be taken into account when zebrafish is used as a model for human cardiac electrophysiology, cardiac diseases, and in screening cardioactive substances.

THEMIS Observations of Unusual Bow Shock Motion, Attending a Transient Magnetospheric Event

NASA Technical Reports Server (NTRS)

Korotova, Galina; Sibeck, David; Omidi, N.; Angelopoulos, V.

2013-01-01

We present a multipoint case study of solar wind and magnetospheric observations during a transient magnetospheric compression at 2319 UT on October 15, 2008. We use high-time resolution magnetic field and plasma data from the THEMIS and GOES-11/12 spacecraft to show that this transient event corresponded to an abrupt rotation in the IMF orientation, a change in the location of the foreshock, and transient outward bow shock motion. We employ results from a global hybrid code model to reconcile the observations indicating transient inward magnetopause motion with the outward bow shock motion.

Turbine and method for reducing shock losses in a turbine

DOEpatents

Ristau, Neil

2015-09-01

A turbine includes a rotor and a casing that circumferentially surrounds at least a portion of the rotor. The rotor and the casing at least partially define a gas path through the turbine. A last stage of rotating blades is circumferentially arranged around the rotor and includes a downstream swept portion radially outward from the rotor. A method for reducing shock losses in a turbine includes removing a last stage of rotating blades circumferentially arranged around a rotor and replacing the last stage of rotating blades with rotating blades having a downstream swept portion radially outward from the rotor.

Turbulence Evolution and Shock Acceleration of Solar Energetic Particles

NASA Technical Reports Server (NTRS)

Chee, Ng K.

2007-01-01

We model the effects of self-excitation/damping and shock transmission of Alfven waves on solar-energetic-particle (SEP) acceleration at a coronal-mass-ejection (CME) driven parallel shock. SEP-excited outward upstream waves speedily bootstrap acceleration. Shock transmission further raises the SEP-excited wave intensities at high wavenumbers but lowers them at low wavenumbers through wavenumber shift. Downstream, SEP excitation of inward waves and damping of outward waves tend to slow acceleration. Nevertheless, > 2000 km/s parallel shocks at approx. 3.5 solar radii can accelerate SEPs to 100 MeV in < 5 minutes.

A numerical calculation of outward propagation of solar disturbances. [solar atmospheric model with shock wave propagation

NASA Technical Reports Server (NTRS)

Wu, S. T.

1974-01-01

The responses of the solar atmosphere due to an outward propagation shock are examined by employing the Lax-Wendroff method to solve the set of nonlinear partial differential equations in the model of the solar atmosphere. It is found that this theoretical model can be used to explain the solar phenomena of surge and spray. A criterion to discriminate the surge and spray is established and detailed information concerning the density, velocity, and temperature distribution with respect to the height and time is presented. The complete computer program is also included.

Angular Distributions of Discrete Mesoscale Mapping Functions

NASA Astrophysics Data System (ADS)

Kroszczyński, Krzysztof

2015-08-01

The paper presents the results of analyses of numerical experiments concerning GPS signal propagation delays in the atmosphere and the discrete mapping functions defined on their basis. The delays were determined using data from the mesoscale non-hydrostatic weather model operated in the Centre of Applied Geomatics, Military University of Technology. A special attention was paid to investigating angular characteristics of GPS slant delays for low angles of elevation. The investigation proved that the temporal and spatial variability of the slant delays depends to a large extent on current weather conditions.

Assessing effects of the e-Chasqui laboratory information system on accuracy and timeliness of bacteriology results in the Peruvian tuberculosis program.

PubMed

Blaya, Joaquin A; Shin, Sonya S; Yagui, Martin J A; Yale, Gloria; Suarez, Carmen; Asencios, Luis; Fraser, Hamish

2007-10-11

We created a web-based laboratory information system, e-Chasqui to connect public laboratories to health centers to improve communication and analysis. After one year, we performed a pre and post assessment of communication delays and found that e-Chasqui maintained the average delay but eliminated delays of over 60 days. Adding digital verification maintained the average delay, but should increase accuracy. We are currently performing a randomized evaluation of the impacts of e-Chasqui.

Formation of M-Like Intermediates in Proteorhodopsin in Alkali Solutions (pH ≥ ∼8.5) Where the Proton Release Occurs First in Contrast to the Sequence at Lower pH.

PubMed

Tamogami, Jun; Sato, Keitaro; Kurokawa, Sukuna; Yamada, Takumi; Nara, Toshifumi; Demura, Makoto; Miyauchi, Seiji; Kikukawa, Takashi; Muneyuki, Eiro; Kamo, Naoki

2016-02-23

Proteorhodopsin (PR) is an outward light-driven proton pump observed in marine eubacteria. Despite many structural and functional similarities to bacteriorhodopsin (BR) in archaea, which also acts as an outward proton pump, the mechanism of the photoinduced proton release and uptake is different between two H(+)-pumps. In this study, we investigated the pH dependence of the photocycle and proton transfer in PR reconstituted with the phospholipid membrane under alkaline conditions. Under these conditions, as the medium pH increased, a blue-shifted photoproduct (defined as Ma), which is different from M, with a pKa of ca. 9.2 was produced. The sequence of the photoinduced proton uptake and release during the photocycle was inverted with the increase in pH. A pKa value of ca. 9.5 was estimated for this inversion and was in good agreement with the pKa value of the formation of Ma (∼ 9.2). In addition, we measured the photoelectric current generated by PRs attached to a thin polymer film at varying pH. Interestingly, increases in the medium pH evoked bidirectional photocurrents, which may imply a possible reversal of the direction of the proton movement at alkaline pH. On the basis of these findings, a putative photocycle and proton transfer scheme in PR under alkaline pH conditions was proposed.

Upper canine inclination influences the aesthetics of a smile.

PubMed

Bothung, C; Fischer, K; Schiffer, H; Springer, I; Wolfart, S

2015-02-01

This current study investigated which angle of canine inclination (angle between canine tooth axis (CA-line) and the line between the lateral canthus and the ipsilateral labial angle (EM-line)) is perceived to be most attractive in a smile. The second objective was to determine whether laymen and dental experts share the same opinion. A Q-sort assessment was performed with 48 posed smile photographs to obtain two models of neutral facial attractiveness. Two sets of images (1 male model set, 1 female model set), each containing seven images with incrementally altered canine and posterior teeth inclinations, were generated. The images were ranked for attractiveness by three groups (61 laymen, 59 orthodontists, 60 dentists). The images with 0° inclination, that is CA-line (maxillary canine axis) parallel to EM-line (the line formed by the lateral canthus and the ipsilateral corner of the mouth) (male model set: 54·4%; female model set: 38·9%), or -5° (inward) inclination (male model set: 20%; female model set: 29·4%) were perceived to be most attractive within each set. Images showing inward canine inclinations were regarded to be more attractive than those with outward inclinations. Dental experts and laymen were in accordance with the aesthetics. Smiles were perceived to be most attractive when the upper canine tooth axis was parallel to the EM-line. In reconstructive or orthodontic therapy, it is thus important to incline canines more inwardly than outwardly. © 2014 John Wiley & Sons Ltd.

Multidimensional pair-instability supernova simulations and their multi-messenger signals

NASA Astrophysics Data System (ADS)

Gilmer, Matthew; Kozyreva, Alexandra; Hirschi, Raphael; Fröhlich, Carla; Wright, Warren; Kneller, James P.; Yusof, Norhasliza

2018-01-01

Pair-Instability supernovae (PISNe) are an exotic class of supernovae which, in addition to being fascinating in its own right (its very existence is a topic of debate), may be important for many areas of astrophysics (early stellar populations, galaxy/chemical evolution, cosmic reionization, etc.). At present, PISNe are one of the three proposed mechanisms for explaining superluminous supernovae, though one major drawback is that PISN models predict longer rise times to peak luminosity than seen in observations of superluminous supernovae. Model rise times can be reduced by having shallower progenitor envelopes and/or outward mixing of radioactive material during the explosions. Here, we present explosions and light curves for four progenitor models, with relatively shallow envelopes, that span the PISN mass range. Our light curves exhibit significantly shorter rise times than other PISNe light curves. In addition, we investigate the effects of a multidimensional treatment during the explosive burning phase of PISNe, including the first such treatment in 3D. We find a small amount of outward mixing of radioactive Ni-56 that increases with the number of dimensions, however this mixing is insufficient to significantly alter the light curve rise time. We find significant mixing between the silicon and oxygen rich layers, especially in 3D, that may affect model spectra and should be investigated in the future. Finally, we present the neutrino signals expected from our most massive and least massive PISN models. Accounting for neutrino oscillations, we compute the expected event rates for current and future neutrino detectors.

Reflection of Fast Magnetosonic Waves near a Magnetic Reconnection Region

NASA Astrophysics Data System (ADS)

Provornikova, E.; Laming, J. M.; Lukin, V. S.

2018-06-01

Magnetic reconnection in the solar corona is thought to be unstable with the formation of multiple interacting plasmoids, and previous studies have shown that plasmoid dynamics can trigger MHD waves of different modes propagating outward from the reconnection site. However, variations in plasma parameters and magnetic field strength in the vicinity of a coronal reconnection site may lead to wave reflection and mode conversion. In this paper we investigate the reflection and refraction of fast magnetoacoustic waves near a reconnection site. Under a justified assumption of an analytically specified Alfvén speed profile, we derive and solve analytically the full wave equation governing the propagation of fast-mode waves in a non-uniform background plasma without recourse to the small wavelength approximation. We show that the waves undergo reflection near the reconnection current sheet due to the Alfvén speed gradient and that the reflection efficiency depends on the plasma-β parameter, as well as on the wave frequency. In particular, we find that waves are reflected more efficiently near reconnection sites in a low-β plasma, which is typical under solar coronal conditions. Also, the reflection is larger for lower-frequency waves while high-frequency waves propagate outward from the reconnection region almost without the reflection. We discuss the implications of efficient wave reflection near magnetic reconnection sites in strongly magnetized coronal plasma for particle acceleration, and also the effect this might have on first ionization potential (FIP) fractionation by the ponderomotive force of these waves in the chromosphere.

Modeling of delays in PKPD: classical approaches and a tutorial for delay differential equations.

PubMed

Koch, Gilbert; Krzyzanski, Wojciech; Pérez-Ruixo, Juan Jose; Schropp, Johannes

2014-08-01

In pharmacokinetics/pharmacodynamics (PKPD) the measured response is often delayed relative to drug administration, individuals in a population have a certain lifespan until they maturate or the change of biomarkers does not immediately affects the primary endpoint. The classical approach in PKPD is to apply transit compartment models (TCM) based on ordinary differential equations to handle such delays. However, an alternative approach to deal with delays are delay differential equations (DDE). DDEs feature additional flexibility and properties, realize more complex dynamics and can complementary be used together with TCMs. We introduce several delay based PKPD models and investigate mathematical properties of general DDE based models, which serve as subunits in order to build larger PKPD models. Finally, we review current PKPD software with respect to the implementation of DDEs for PKPD analysis.

Factors Associated with Delayed Tuberculosis Test-seeking Behavior in the Peruvian Amazon

PubMed Central

Ford, Carolyn M.; Bayer, Angela M.; Gilman, Robert H.; Onifade, Dami; Acosta, Colleen; Cabrera, Lilia; Vidal, Carlos; Evans, Carlton A.

2010-01-01

This study aimed to determine the psychosocial factors associated with delayed test-seeking among tuberculosis patients. The duration of symptoms before seeking medical care was assessed by interview for 108 newly diagnosed pulmonary tuberculosis patients in the city of Iquitos in the Peruvian Amazon, which has high tuberculosis incidence. Beliefs associated with test-seeking behavior and delay was assessed in these patients. The median delay from symptom onset to seeking diagnostic testing was 61 days (inter-quartile range 30–91 days). The belief that tuberculosis is curable was associated with a 100% longer test-seeking delay; the perception that tuberculosis was common was associated with a 57% longer delay; male gender was associated with a 48% longer delay; and education less than complete secondary schooling was associated with a 44% longer delay. In conclusion, current health promotion activities that emphasize tuberculosis curability and high prevalence may paradoxically increase test-seeking delay and therefore require prospective evaluation. PMID:19996443

Measurement method for determining the magnetic hysteresis effects of reluctance actuators by evaluation of the force and flux variation.

PubMed

Vrijsen, N H; Jansen, J W; Compter, J C; Lomonova, E A

2013-07-01

A measurement method is presented which identifies the magnetic hysteresis effects present in the force of linear reluctance actuators. The measurement method is applied to determine the magnetic hysteresis in the force of an E-core reluctance actuator, with and without pre-biasing permanent magnet. The force measurements are conducted with a piezoelectric load cell (Kistler type 9272). This high-bandwidth force measurement instrument is identified in the frequency domain using a voice-coil actuator that has negligible magnetic hysteresis and eddy currents. Specifically, the phase delay between the current and force of the voice-coil actuator is used for the calibration of the measurement instrument. This phase delay is also obtained by evaluation of the measured force and flux variation in the E-core actuator, both with and without permanent magnet on the middle tooth. The measured magnetic flux variation is used to distinguish the phase delay due to magnetic hysteresis from the measured phase delay between the current and the force of the E-core actuator. Finally, an open loop steady-state ac model is presented that predicts the magnetic hysteresis effects in the force of the E-core actuator.

Exploring Opportunities to Boost Adult Students' Graduation--The Reasons behind the Delays and Drop-Outs of Graduation

ERIC Educational Resources Information Center

Aarreniemi-Jokipelto, Päivi; Bäck, Asta

2014-01-01

Drop-outs and delays of graduation is currently a huge problem in adult education. The main reason for the drop-outs and delays is usually stated to be the difficulty of combining studies with family and work. This study was based on interviews where students studying in the bachelor's or master's degree programme were interviewed to find out the…

On-demand SSRI treatment of premature ejaculation: pharmacodynamic limitations for relevant ejaculation delay and consequent solutions.

PubMed

Waldinger, Marcel D; Schweitzer, Dave H; Olivier, Berend

2005-01-01

Recently, the idea has emerged that on-demand use of serotonin reuptake inhibitors (SSRIs), particularly short half-life, should be equally effective in delaying ejaculation as daily SSRI treatment of premature ejaculation. To provide evidence that SSRI-induced ejaculation delay is mainly dependent on pharmacodynamic properties of the drug and hardly on pharmacokinetic factors, and that combined SSRI administration with specific 5-hydroxytryptamine (5-HT) receptor antagonism leads acutely to stronger ejaculation delay than acute SSRI monoadministration. We performed a detailed analysis of serotonin neurotransmission and reviewed animal studies with 5-HT(1A) receptor antagonists. In addition, we critically reviewed existing on-demand SSRI treatments publications and the current debate on a definition of premature ejaculation. Intravaginal ejaculation latency time (IELT). Acute SSRI administration leads to only a mild or no increase of 5-HT neurotransmission and concomitant stimulation of postsynaptic 5-HT receptors. Existing on-demand SSRI treatment studies suffer from methodological insufficiencies, and the reported high-fold increases of ejaculation time contradict with neuropharmacological insights from serotonin metabolism. Animal studies show that SSRI coadministration with 5-HT(1A) receptor antagonists significantly increases the ejaculation time acutely compared to acute SSRI monoadministration. On-demand SSRI treatment has less ejaculation-delaying effects than daily SSRI treatment. SSRIs with a short half-life are likely leading to much less ejaculation delay than current registered SSRIs. Combined use of SSRIs with 5-HT(1A) receptor antagonists increases the likelihood of clinically relevant ejaculation delay after on-demand treatment. On-demand SSRIs with short half-life that insufficiently delay ejaculation in men with IELTs less than 1 minute should be called ejaculation-delaying drugs rather than drugs against premature ejaculation.

Differential responses of rabbit ventricular and atrial transient outward current (Ito) to the Ito modulator NS5806.

PubMed

Cheng, Hongwei; Cannell, Mark B; Hancox, Jules C

2017-03-01

Transient outward potassium current (I to ) in the heart underlies phase 1 repolarization of cardiac action potentials and thereby affects excitation-contraction coupling. Small molecule activators of I to may therefore offer novel treatments for cardiac dysfunction, including heart failure and atrial fibrillation. NS5806 has been identified as a prototypic activator of canine I to This study investigated, for the first time, actions of NS5806 on rabbit atrial and ventricular I to Whole cell patch-clamp recordings of I to and action potentials were made at physiological temperature from rabbit ventricular and atrial myocytes. 10  μ mol/L NS5806 increased ventricular I to with a leftward shift in I to activation and accelerated restitution. At higher concentrations, stimulation of I to was followed by inhibition. The EC 50 for stimulation was 1.6  μ mol/L and inhibition had an IC 50 of 40.7  μ mol/L. NS5806 only inhibited atrial I to (IC 50 of 18  μ mol/L) and produced a modest leftward shifts in I to activation and inactivation, without an effect on restitution. 10  μ mol/L NS5806 shortened ventricular action potential duration (APD) at APD 20 -APD 90 but prolonged atrial APD NS5806 also reduced atrial AP upstroke and amplitude, consistent with an additional atrio-selective effect on Na + channels. In contrast to NS5806, flecainide, which discriminates between Kv1.4 and 4.x channels, produced similar levels of inhibition of ventricular and atrial I to NS5806 discriminates between rabbit ventricular and atrial I to, with mixed activator and inhibitor actions on the former and inhibitor actions against the later. NS5806 may be of significant value for pharmacological interrogation of regional differences in native cardiac I to . © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.