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Sample records for a-type potassium currents

  1. Up-regulation of A-type potassium currents protects neurons against cerebral ischemia

    PubMed Central

    Deng, Ping; Pang, Zhi-Ping; Lei, Zhigang; Shikano, Sojin; Xiong, Qiaojie; Harvey, Brandon K; London, Barry; Wang, Yun; Li, Min; Xu, Zao C

    2011-01-01

    Excitotoxicity is the major cause of many neurologic disorders including stroke. Potassium currents modulate neuronal excitability and therefore influence the pathological process. A-type potassium current (IA) is one of the major voltage-dependent potassium currents, yet its roles in excitotoxic cell death are not well understood. We report that, following ischemic insults, the IA increases significantly in large aspiny (LA) neurons but not medium spiny (MS) neurons in the striatum, which correlates with the higher resistance of LA neurons to ischemia. Activation of protein kinase Cα increases IA in LA neurons after ischemia. Cultured neurons from transgenic mice lacking both Kv1.4 and Kv4.2 subunits exhibit an increased vulnerability to ischemic insults. Increase of IA by recombinant expression of Kv1.4 or Kv4.2 is sufficient in improving the survival of MS neurons against ischemic insults both in vitro and in vivo. These results, taken together, provide compelling evidence for a protective role of IA against ischemia. PMID:21673715

  2. Na+ and Ca2+ cooperatively down regulate the A-type potassium currents in Helix neurons.

    PubMed

    Erdélyi, L

    1995-01-01

    Modulatory actions of Na+, Tris+, Li+ and Ca2+ on A-type potassium currents were investigated in identified neurons of the snail, Helix pomatia L. A-currents were isolated under spike threshold voltages by use of the double pulse method in combination with computer techniques. To estimate the action of Na+ on A-type potassium currents the normal physiological solution was changed to Na-free (mannitol) medium which increased the amplitude of the A-currents at -30 mV membrane potential by 20.5% without significant modulation of the time-dependent inactivation. When Tris-HCl or LiCl substituted for NaCl, the amplitude of the A-currents decreased by 27.5 or 32.5%, respectively. Li+ did not modify the time constant of decay of the A-currents, but Tris+ decreased it by 15.8%. There was an increase of the amplitude of the A-currents in the Na-, Ca-free (Tris) medium relative to the Na-free (Tris) solution by 27.7% and a decrease of the time constant of decay by 25.3%. It is concluded that A-currents are down regulated by Na+ and Ca2+ under physiological circumstances, but the modulatory action of Ca2+ is more complex and influences the amplitude, time-dependent inactivation and potential-dependent inactivation characteristics of IA. Among monovalent cations, the A-current attenuation increases in the sequence of Na+ < Tris+ < Li+. All identified neurons react in a similar way but with different sensitivities.

  3. Functional role of A-type potassium currents in rat presympathetic PVN neurones

    PubMed Central

    Sonner, Patrick M; Stern, Javier E

    2007-01-01

    Despite the fact that paraventricular nucleus (PVN) neurones innervating the rostral ventrolateral medulla (RVLM) play important roles in the control of sympathetic function both in physiological and pathological conditions, the precise mechanisms controlling their activity are still incompletely understood. In the present study, we evaluated whether the transient outward potassium current IA is expressed in PVN-RVLM neurones, characterized its biophysical and pharmacological properties, and determined its role in shaping action potentials and firing discharge in these neurones. Patch-clamp recordings obtained from retrogradely labelled, PVN-RVLM neurones indicate that a 4-AP sensitive, TEA insensitive current, with biophysical properties consistent with IA, is present in these neurones. Pharmacological blockade of IA depolarized resting Vm and prolonged Na+ action potential duration, by increasing its width and by slowing down its decay time course. Interestingly, blockade of IA either increased or decreased the firing activity of PVN-RVLM neurones, supporting the presence of subsets of PVN-RVLM neurones differentially modulated by IA. In all cases, the effects of IA on firing activity were prevented by a broad spectrum Ca2+ channel blocker. Immunohistochemical studies suggest that IA in PVN-RVLM neurons is mediated by Kv1.4 and/or Kv4.3 channel subunits. Overall, our results demonstrate the presence of IA in PVN-RVLM neurones, which actively modulates their action potential waveform and firing activity. These studies support IA as an important intrinsic mechanism controlling neuronal excitability in this central presympathetic neuronal population. PMID:17525115

  4. A-Type potassium currents active at subthreshold potentials in mouse cerebellar purkinje cells

    PubMed Central

    Sacco, Tiziana; Tempia, Filippo

    2002-01-01

    Voltage-dependent and calcium-independent K+ currents were whole-cell recorded from cerebellar Purkinje cells in slices. Tetraethylammonium (TEA, 4 mm) application isolated an A-type K+ current (Ik(a)) with a peak amplitude, at +20 mV, of about one third of the total voltage-dependent and calcium-independent K+ current. The Ik(a) activated at about −60 mV, had a V0.5 of activation of −24.9 mV and a V0.5 of inactivation of −69.2 mV. The deactivation time constant at −70 mV was 3.4 ± 0.4 ms, while the activation time constant at +20 mV was 0.9 ± 0.2 ms. The inactivation kinetics was weakly voltage dependent, with two time constants; those at +20 mV were 19.3 ± 3.1 and 97.6 ± 9.8 ms. The recovery from inactivation had two time constants of 60.8 ms (78.4%) and 962.3 ms (21.6%). The Ik(a) was blocked by 4-aminopyridine with an IC50 of 67.6 μM. Agitoxin-2 (2 nm) blocked 17.4 ± 2.1% of the Ik(a). Flecainide completely blocked the Ik(a) with a biphasic effect with IC50 values of 4.4 and 183.2 μM. In current-clamp recordings the duration of evoked action potentials was affected neither by agitoxin-2 (2 nm) nor by flecainide (3 μM), but action potentials that were already broadened by TEA were further prolonged by 4-aminopyridine (100 μM). The amplitude of the hyperpolarisation at the end of depolarising steps was reduced by all these blockers. PMID:12205185

  5. 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

  6. Dynamic, Nonlinear Feedback Regulation of Slow Pacemaking by A-Type Potassium Current in Ventral Tegmental Area Neurons

    PubMed Central

    Khaliq, Zayd M.; Bean, Bruce P.

    2010-01-01

    We analyzed ionic currents that regulate pacemaking in dopaminergic neurons of the mouse ventral tegmental area by comparing voltage trajectories during spontaneous firing with ramp-evoked currents in voltage clamp. Most recordings were made in brain slice, with key experiments repeated using acutely dissociated neurons, which gave identical results. During spontaneous firing, net ionic current flowing between spikes was calculated from the time derivative of voltage multiplied by cell capacitance, signal-averaged over many firing cycles to enhance resolution. Net inward interspike current had a distinctive nonmonotonic shape, reaching a minimum (generally <1 pA) between −60 and −55 mV. Under voltage clamp, ramps over subthreshold voltages elicited a time- and voltage-dependent outward current that peaked near −55 mV. This current was undetectable with 5 mV/s ramps and increased steeply with depolarization rate over the range (10 –50 mV/s) typical of natural pacemaking. Ramp-evoked subthreshold current was resistant to α-dendrotoxin, paxilline, apamin, and tetraethylammonium but sensitive to 4-aminopyridine and 0.5 mM Ba2+, consistent with A-type potassium current (IA). Same-cell comparison of currents elicited by various ramp speeds with natural spontaneous depolarization showed how the steep dependence of IA on depolarization rate results in small net inward currents during pacemaking. These results reveal a mechanism in which subthreshold IA is near zero at steady state, but is engaged at depolarization rates >10 mV/s to act as a powerful, supralinear feedback element. This feedback mechanism explains how net ionic current can be constrained to <1–2 pA but reliably inward, thus enabling slow, regular firing. PMID:18945898

  7. Diminished A-type potassium current and altered firing properties in presympathetic PVN neurones in renovascular hypertensive rats.

    PubMed

    Sonner, Patrick M; Filosa, Jessica A; Stern, Javier E

    2008-03-15

    Accumulating evidence supports a contribution of the hypothalamic paraventricular nucleus (PVN) to sympathoexcitation and elevated blood pressure in renovascular hypertension. However, the underlying mechanisms resulting in altered neuronal function in hypertensive rats remain largely unknown. Here, we aimed to address whether the transient outward potassium current (I(A)) in identified rostral ventrolateral medulla (RVLM)-projecting PVN neurones is altered in hypertensive rats, and whether such changes affected single and repetitive action potential properties and associated changes in intracellular Ca(2+) levels. Patch-clamp recordings obtained from PVN-RVLM neurons showed a reduction in I(A) current magnitude and single channel conductance, and an enhanced steady-state current inactivation in hypertensive rats. Morphometric reconstructions of intracellularly labelled PVN-RVLM neurons showed a diminished dendritic surface area in hypertensive rats. Consistent with a diminished I(A) availability, action potentials in PVN-RVLM neurons in hypertensive rats were broader, decayed more slowly, and were less sensitive to the K(+) channel blocker 4-aminopyridine. Simultaneous patch clamp recordings and confocal Ca(2+) imaging demonstrated enhanced action potential-evoked intracellular Ca(2+) transients in hypertensive rats. Finally, spike broadening during repetitive firing discharge was enhanced in PVN-RVLM neurons from hypertensive rats. Altogether, our results indicate that diminished I(A) availability constitutes a contributing mechanism underlying aberrant central neuronal function in renovascular hypertension.

  8. Calcium-calmodulin-dependent kinase II modulates Kv4.2 channel expression and upregulates neuronal A-type potassium currents.

    PubMed

    Varga, Andrew W; Yuan, Li-Lian; Anderson, Anne E; Schrader, Laura A; Wu, Gang-Yi; Gatchel, Jennifer R; Johnston, Daniel; Sweatt, J David

    2004-04-07

    Calcium-calmodulin-dependent kinase II (CaMKII) has a long history of involvement in synaptic plasticity, yet little focus has been given to potassium channels as CaMKII targets despite their importance in repolarizing EPSPs and action potentials and regulating neuronal membrane excitability. We now show that Kv4.2 acts as a substrate for CaMKII in vitro and have identified CaMKII phosphorylation sites as Ser438 and Ser459. To test whether CaMKII phosphorylation of Kv4.2 affects channel biophysics, we expressed wild-type or mutant Kv4.2 and the K(+) channel interacting protein, KChIP3, with or without a constitutively active form of CaMKII in Xenopus oocytes and measured the voltage dependence of activation and inactivation in each of these conditions. CaMKII phosphorylation had no effect on channel biophysical properties. However, we found that levels of Kv4.2 protein are increased with CaMKII phosphorylation in transfected COS cells, an effect attributable to direct channel phosphorylation based on site-directed mutagenesis studies. We also obtained corroborating physiological data showing increased surface A-type channel expression as revealed by increases in peak K(+) current amplitudes with CaMKII phosphorylation. Furthermore, endogenous A-currents in hippocampal pyramidal neurons were increased in amplitude after introduction of constitutively active CaMKII, which results in a decrease in neuronal excitability in response to current injections. Thus CaMKII can directly modulate neuronal excitability by increasing cell-surface expression of A-type K(+) channels.

  9. 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

  10. ANEPIII, a new recombinant neurotoxic polypeptide derived from scorpion peptide, inhibits delayed rectifier, but not A-type potassium currents in rat primary cultured hippocampal and cortical neurons.

    PubMed

    Li, Chun-Li; Zhang, Jing-Hai; Yang, Bao-Feng; Jiao, Jun-Dong; Wang, Ling; Wu, Chun-Fu

    2006-01-15

    A new recombinant neurotoxic polypeptide ANEPIII (BmK ANEPIII) derived from Scorpion peptide, which was demonstrated with antineuroexcitation properties in animal models, was examined for its action on K+ currents in primary cultured rat hippocampal and cortical neurons using the patch clamp technique in the whole-cell configuration. The delayed rectifier K+ current (I(k)) was inhibited by externally applied recombinant BmK ANEPIII, while the transient A-current (I(A)) remained virtually unaffected. BmK ANEPIII 3 microM, reduced the delayed rectifier current by 28.2% and 23.6% in cultured rat hippocampal and cortical neurons, respectively. The concentration of half-maximal block was 155.1 nM for hippocampal neurons and 227.2 nM for cortical neurons, respectively. These results suggest that BmK ANEPIII affect K+ currents, which may lead to a reduction in neuronal excitability.

  11. Reduced potassium currents in old rat CA1 hippocampal neurons.

    PubMed

    Alshuaib, W B; Hasan, S M; Cherian, S P; Mathew, M V; Hasan, M Y; Fahim, M A

    2001-01-15

    Potassium currents are an important factor in repolarizing the membrane potential and determining the level of neuronal excitability. We compared potassium currents in CA1 hippocampal neurons dissociated from young (2-3 months old) and old (26-30 months old) Sprague-Dawley rats. Whole-cell patch-clamp techniques were used to measure the delayed rectifier (sustained) and the A-type (transient) potassium currents. The delayed rectifier current was smaller in old (548 +/- 57 pA) than in young (1193 +/- 171 pA) neurons. In the absence of extracellular calcium, the delayed rectifier current was also smaller in old (427 +/- 41 pA) than in young (946 +/- 144 pA) neurons. The cell membrane capacitance was unchanged in old (13.3 +/- 1.2 pF) compared to young (13.6 +/- 1.2 pF). Therefore, the reduction in the delayed rectifier current was not due to a change in membrane surface area. Moreover, activation and inactivation of the delayed rectifier current were unchanged in old compared to young neurons. The slope of the current-voltage relation, however, was smaller in old (B = 5.03) than in young (B = 9.62) neurons. Similarly, the A-current was smaller in old (100 +/- 16 pA) than in young (210 +/- 44 pA) neurons in the presence of extracellular calcium. This reduction of potassium currents could account for the prolongation of action potentials reported previously for old rat CA1 hippocampal neurons. The age-related reduction in potassium current indicates plasticity in neuronal function that can impact communication in the hippocampal neural network during aging.

  12. Shaker and Shal Mediate Transient Calcium-Independent Potassium Current in a Drosophila Flight Motoneuron

    PubMed Central

    Duch, Carsten

    2009-01-01

    Ionic currents underlie the firing patterns, excitability, and synaptic integration of neurons. Despite complete sequence information in multiple species, our knowledge about ion channel function in central neurons remains incomplete. This study analyzes the potassium currents of an identified Drosophila flight motoneuron, MN5, in situ. MN5 exhibits four different potassium currents, two fast-activating transient ones and two sustained ones, one of each is calcium activated. Pharmacological and genetic manipulations unravel the specific contributions of Shaker and Shal to the calcium independent transient A-type potassium currents. α-dendrotoxin (Shaker specific) and phrixotoxin-2 (Shal specific) block different portions of the transient calcium independent A-type potassium current. Following targeted expression of a Shaker dominant negative transgene in MN5, the remaining A-type potassium current is α-dendrotoxin insensitive. In Shal RNAi knock down the remaining A-type potassium current is phrixotoxin-2 insensitive. Additionally, barium blocks calcium-activated potassium currents but also a large portion of phrixotoxin-2-sensitive A-type currents. Targeted knock down of Shaker or Shal channels each cause identical reduction in total potassium current amplitude as acute application of α-dendrotoxin or phrixotoxin-2, respectively. This shows that the knock downs do not cause upregulation of potassium channels underlying other A-type channels during development. Immunocytochemistry and targeted expression of modified GFP-tagged Shaker channels with intact targeting sequence in MN5 indicate predominant axonal localization. These data can now be used to investigate the roles of Shaker and Shal for motoneuron intrinsic properties, synaptic integration, and spiking output during behavior by targeted genetic manipulations. PMID:19828724

  13. Amiodarone Inhibits Apamin-Sensitive Potassium Currents

    PubMed Central

    Turker, Isik; Yu, Chih-Chieh; Chang, Po-Cheng; Chen, Zhenhui; Sohma, Yoshiro; Lin, Shien-Fong; Chen, Peng-Sheng; Ai, Tomohiko

    2013-01-01

    Background Apamin sensitive potassium current (IKAS), carried by the type 2 small conductance Ca2+-activated potassium (SK2) channels, plays an important role in post-shock action potential duration (APD) shortening and recurrent spontaneous ventricular fibrillation (VF) in failing ventricles. Objective To test the hypothesis that amiodarone inhibits IKAS in human embryonic kidney 293 (HEK-293) cells. Methods We used the patch-clamp technique to study IKAS in HEK-293 cells transiently expressing human SK2 before and after amiodarone administration. Results Amiodarone inhibited IKAS in a dose-dependent manner (IC50, 2.67±0.25 µM with 1 µM intrapipette Ca2+). Maximal inhibition was observed with 50 µM amiodarone which inhibited 85.6±3.1% of IKAS induced with 1 µM intrapipette Ca2+ (n = 3). IKAS inhibition by amiodarone was not voltage-dependent, but was Ca2+-dependent: 30 µM amiodarone inhibited 81.5±1.9% of IKAS induced with 1 µM Ca2+ (n = 4), and 16.4±4.9% with 250 nM Ca2+ (n = 5). Desethylamiodarone, a major metabolite of amiodarone, also exerts voltage-independent but Ca2+ dependent inhibition of IKAS. Conclusion Both amiodarone and desethylamiodarone inhibit IKAS at therapeutic concentrations. The inhibition is independent of time and voltage, but is dependent on the intracellular Ca2+ concentration. SK2 current inhibition may in part underlie amiodarone's effects in preventing electrical storm in failing ventricles. PMID:23922993

  14. Dendritic A-type potassium channel subunit expression in CA1 hippocampal interneurons.

    PubMed

    Menegola, M; Misonou, H; Vacher, H; Trimmer, J S

    2008-06-26

    Voltage-gated potassium (Kv) channels are important and diverse determinants of neuronal excitability and exhibit specific expression patterns throughout the brain. Among Kv channels, Kv4 channels are major determinants of somatodendritic A-type current and are essential in controlling the amplitude of backpropagating action potentials (BAPs) into neuronal dendrites. BAPs have been well studied in a variety of neurons, and have been recently described in hippocampal and cortical interneurons, a heterogeneous population of GABAergic inhibitory cells that regulate activity of principal cells and neuronal networks. We used well-characterized mouse monoclonal antibodies against the Kv4.3 and potassium channel interacting protein (KChIP) 1 subunits of A-type Kv channels, and antibodies against different interneuron markers in single- and double-label immunohistochemistry experiments to analyze the expression patterns of Kv4.3 and KChIP1 in hippocampal Ammon's horn (CA1) neurons. Immunohistochemistry was performed on 40 mum rat brain sections using nickel-enhanced diaminobenzidine staining or multiple-label immunofluorescence. Our results show that Kv4.3 and KChIP1 component subunits of A-type channels are co-localized in the soma and dendrites of a large number of GABAergic hippocampal interneurons. These subunits co-localize extensively but not completely with markers defining the four major interneuron subpopulations tested (parvalbumin, calbindin, calretinin, and somatostatin). These results suggest that CA1 hippocampal interneurons can be divided in two groups according to the expression of Kv4.3/KChIP1 channel subunits. Antibodies against Kv4.3 and KChIP1 represent an important new tool for identifying a subpopulation of hippocampal interneurons with a unique dendritic A-type channel complement and ability to control BAPs.

  15. Effects of allocryptopine on outward potassium current and slow delayed rectifier potassium current in rabbit myocardium

    PubMed Central

    Fu, Yi-Cheng; Zhang, Yu; Tian, Liu-Yang; Li, Nan; Chen, Xi; Cai, Zhong-Qi; Zhu, Chao; Li, Yang

    2016-01-01

    Objective Allocryptopine (ALL) is an effective alkaloid of Corydalis decumbens (Thunb.) Pers. Papaveraceae and has proved to be anti-arrhythmic. The purpose of our study is to investigate the effects of ALL on transmural repolarizing ionic ingredients of outward potassium current (Ito) and slow delayed rectifier potassium current (IKs). Methods The monophasic action potential (MAP) technique was used to record the MAP duration of the epicardium (Epi), myocardium (M) and endocardium (Endo) of the rabbit heart and the whole cell patch clamp was used to record Ito and IKs in cardiomyocytes of Epi, M and Endo layers that were isolated from rabbit ventricles. Results The effects of ALL on MAP of Epi, M and Endo layers were disequilibrium. ALL could effectively reduce the transmural dispersion of repolarization (TDR) in rabbit transmural ventricular wall. ALL decreased the current densities of Ito and IKs in a voltage and concentration dependent way and narrowed the repolarizing differences among three layers. The analysis of gating kinetics showed ALL accelerated the channel activation of Ito in M layers and partly inhibit the channel openings of Ito in Epi, M and Endo cells. On the other hand, ALL mainly slowed channel deactivation of IKs channel in Epi and Endo layers without affecting its activation. Conclusions Our study gives partially explanation about the mechanisms of transmural inhibition of Ito and IKs channels by ALL in rabbit myocardium. These findings provide novel perspective regarding the anti-arrhythmogenesis application of ALL in clinical settings. PMID:27403141

  16. Dendritic A-type potassium channel subunit expression in CA1 hippocampal interneurons

    PubMed Central

    Menegola, Milena; Misonou, Hiroaki; Vacher, Helene; Trimmer, James S.

    2008-01-01

    Voltage-gated potassium (Kv) channels are important and diverse determinants of neuronal excitability and exhibit specific expression patterns throughout the brain. Among Kv channels, Kv4 channels are major determinants of somatodendritic A-type current and are essential in controlling the amplitude of backpropagating action potentials (BAPs) into neuronal dendrites. BAPs have been well studied in a variety of neurons, and have been recently described in hippocampal and cortical interneurons, a heterogeneous population of GABAergic inhibitory cells that regulate activity of principal cells and neuronal networks. We used well-characterized mouse monoclonal antibodies against the Kv4.3 and KChIP1 subunits of A-type Kv channels, and antibodies against different interneuron markers in single- and double-label immunohistochemistry experiments to analyze the expression patterns of Kv4.3 and KChIP1 in hippocampal CA1 neurons. Immunohistochemistry was performed on 40 μm rat brain sections using nickel-enhanced diaminobenzidine staining or multiple-label immunofluorescence. Our results show that Kv4.3 and KChIP1 component subunits of A-type channels are co-localized in the soma and dendrites of a large number of GABAergic hippocampal interneurons. These subunits co-localize extensively but not completely with markers defining the four major interneuron subpopulations tested (parvalbumin, calbindin, calretinin, and somatostatin). These results suggest that CA1 hippocampal interneurons can be divided in two groups according to the expression of Kv4.3/KChIP1 channel subunits. Antibodies against Kv4.3 and KChIP1 represent an important new tool for identifying a subpopulation of hippocampal interneurons with unique dendritic A-type channel complement and ability to control BAPs. PMID:18495361

  17. Reduction of voltage-operated potassium currents by levetiracetam: a novel antiepileptic mechanism of action?

    PubMed

    Madeja, Michael; Margineanu, Doru Georg; Gorji, Ali; Siep, Elke; Boerrigter, Paul; Klitgaard, Henrik; Speckmann, Erwin-Josef

    2003-10-01

    Levetiracetam (ucb L059; Keppra) is a novel antiepileptic drug. Its effects on action potential generation and voltage-operated potassium currents were studied in acutely isolated hippocampal CA1 neurones from rat and guinea pig, using the patch-clamp technique in the whole-cell configuration. (i) Levetiracetam reduced repetitive action potential generation and affected the single action potential. Levetiracetam, 100 microM, decreased the total number of action potentials and reduced the total depolarisation area of repetitive action potentials by 21%. Furthermore, levetiracetam increased the duration of the first action potential slightly, prolonged that of the second action potential by 13% and decreased the slope of rise by 23%. (ii) Levetiracetam decreased the voltage-operated potassium current. Without effect on sodium and A-type potassium currents, levetiracetam, 100 microM, reduced the delayed rectifier current by 26%. The concentration of half-maximal block was 47 microM for guinea pig and 6 microM for rat neurones. Thus, the reduction of repetitive action potential generation by levetiracetam can be attributed, unexpectedly, to a moderate reduction of the delayed rectifier potassium current, as supported by a simulation of action potential generation. This suggests that a reduction of potassium currents may contribute to the antiepileptic effect(s) of levetiracetam.

  18. Potassium currents in adult rat intracardiac neurones.

    PubMed Central

    Xi-Moy, S X; Dun, N J

    1995-01-01

    1. Properties of K+ currents were studied in isolated adult rat parasympathetic intracardiac neurones with the use of single-electrode voltage-clamp techniques. 2. A hyperpolarization-activated inward rectifier current was revealed when the membrane was clamped close to the resting level (-60 mV). The slowly developing inward relaxation had a mean amplitude of 450 pA at -150 mV, an activation threshold of -60 to -70 mV and a relaxation time constant of 41 ms at -120 mV. The current was reversibly blocked by Cs+ (1 mM) and became smaller with reduced [K+]o and [Na+]o, indicating that this inward rectifier current probably is a time- and voltage-dependent Na(+)-K+ current. 3. Step depolarizations from the holding potential of -80 mV evoked a transient (< 100 ms at -40 mV) outward K+ current (IA) which was blocked by 4-aminopyridine (4-AP, 1 mM). The time constants for IA inactivation were 20 ms at -50 mV and 16 ms at -20 mV. The steady-state activation and (removal of) inactivation curve showed a small overlap between -70 and -40 mV; the reversal potential of IA was close to EK. 4. Step hyperpolarizations from the depolarized potentials, i.e. -30 mV, revealed a slow inward relaxation associated with the deactivation of a time- and voltage-dependent current. The inward relaxation became faster at more hyperpolarized potentials and reversed at -85 and -53 mV in 4.7 and 15 mM [K+]o. This current was blocked by muscarine (20 microM) and Ba2+ (1 mM) but not affected by Cs+ (1 mM); this current may correspond to the M-current (IM). 5. Depolarization-activated outward K+ currents were evoked by holding the membrane close to the resting potential in the presence of tetrodotoxin (TTX, 3 microM), 4-AP (1 mM) and Ba2+ (1 mM). The amplitude of the outward relaxation and the tail current became smaller as the [K+]o was elevated. The outward tail current was reduced in a Ca(2+)-free solution and the residual current was eliminated by the addition of tetraethylammonium (TEA, 10 m

  19. Muscarinic modulation of erg potassium current

    PubMed Central

    Hirdes, Wiebke; Horowitz, Lisa F; Hille, Bertil

    2004-01-01

    We studied modulation of current in human embryonic kidney tsA-201 cells coexpressing rat erg1 channels with M1 muscarinic receptors. Maximal current was inhibited 30% during muscarinic receptor stimulation, with a small positive shift of the midpoint of activation. Inhibition was attenuated by coexpression of the regulator of G-protein signalling RGS2 or of a dominant-negative protein, Gq, but not by N-ethylmaleimide or C3 toxin. Overexpression of a constitutively active form of Gq (but not of G13 or of Gs) abolished the erg current. Hence it is likely that Gq/11, and not Gi/o or G13, mediates muscarinic inhibition. Muscarinic suppression of erg was attenuated by chelating intracellular Ca2+ to < 1 nm free Ca2+ with 20 mm BAPTA in the pipette, but suppression was normal if internal Ca2+ was strongly clamped to a 129 nm free Ca2+ level with a BAPTA buffer and this was combined with numerous other measures to prevent intracellular Ca2+ transients (pentosan polysulphate, preincubation with thapsigargin, and removal of extracellular Ca2+). Hence a minimum amount of Ca2+ was necessary for the inhibition, but a Ca2+ elevation was not. The ATP analogue AMP-PCP did not prevent inhibition. The protein kinase C (PKC) blockers staurosporine and bisindolylmaleimide I did not prevent inhibition, and the PKC-activating phorbol ester PMA did not mimic it. Neither the tyrosine kinase inhibitor genistein nor the tyrosine phosphatase inhibitor dephostatin prevented inhibition by oxotremorine-M. Hence protein kinases are not needed. Experiments with a high concentration of wortmannin were consistent with recovery being partially dependent on PIP2 resynthesis. Wortmannin did not prevent muscarinic inhibition. Our studies of muscarinic inhibition of erg current suggest a role for phospholipase C, but not the classical downstream messengers, such as PKC or a calcium transient. PMID:15235086

  20. Facilitation of calcium-dependent potassium current.

    PubMed

    Thompson, S H

    1994-12-01

    The activation of Ca-dependent K+ current, Ic, was studied in macropatches on the cell bodies of molluscan neurons. When a depolarizing voltage-clamp pulse was applied repeatedly, Ic facilitated in a manner that resembled the facilitation of synaptic transmitter release. Facilitation was characterized by an increase in Ic amplitude, a progressive increase in instantaneous outward current, and a decrease in utilization time. Experiments were done to investigate the mechanism responsible for Ic facilitation. Facilitation was reduced by microinjection of an exogenous Ca2+ buffer into the cytoplasm, indicating that facilitation is a Ca(2+)-dependent process. It was also reduced at elevated temperatures. Conversely, facilitation was greatly potentiated by blocking the Na/Ca exchange mechanism. It is concluded that the facilitation of Ca-dependent K+ current results from the accumulation of Ca2+ at the inner face of the membrane during the repeated activation of Ca2+ channels by depolarization. The Ca2+ indicator fluo-3 was used in fluorescence imaging experiments to measure changes in [Ca]i near the cell membrane during repeated depolarizing pulses and the interpretation of these results was aided by numerical simulations of Ca2+ accumulation, diffusion, and buffering in the peripheral cytoplasm. These experiments showed that the time course of Ic facilitation matches the time course of Ca2+ accumulation at the membrane. It was found that the strength of Ic facilitation varies among patches on the same neuron, suggesting that the accumulation of Ca2+ is not uniform along the inner surface of the membrane and that gradients in [Ca]i develop and are maintained during trains of depolarizing pulses. Potential mechanisms that may lead to local differences in Ca2+ accumulation and Ic facilitation are discussed.

  1. Decreased voltage-gated potassium currents in rat dorsal root ganglion neurons after chronic constriction injury.

    PubMed

    Xiao, Yun; Wu, Yang; Zhao, Bo; Xia, Zhongyuan

    2016-01-20

    Voltage-gated potassium channels (KV) regulate pain transmission by controlling neuronal excitability. Changes in KV expression patterns may thus contribute toward hyperalgesia following nerve injury. The aim of this study was to characterize KV current density in dorsal root ganglion (DRG) neurons following chronic constriction injury (CCI) of the right sciatic nerve, a robust model of post-traumatic neuropathic pain. The study examined changes in small-diameter potassium ion currents (<30 µm) in neurons in the L4-L6 DRG following CCI by whole-cell patch-clamping and the association with post-CCI mechanical and thermal nociceptive thresholds. Compared with the control group, 7 days after CCI, the mechanical force and temperature required to elicit ipsilateral foot withdrawal decreased significantly, indicating tactile allodynia and thermal hyperalgesia. Post-CCI neurons had a significantly lower rheobase current and depolarized resting membrane potential than controls, suggesting KV current downregulation. Some ipsilateral DRG neurons also had spontaneous action potentials and repetitive firing. There was a 55% reduction in the total KV current density caused by a 55% decrease in the sustained delayed rectifier potassium ion current (IK) density and a 17% decrease in the transient A-type potassium ion current (IA) density. These results indicated that changes in DRG neuron IK and IA current density and concomitant afferent hyperexcitability may contribute toward neuropathic pain following injury. The rat CCI model may prove valuable for examining pathogenic mechanisms and potential therapies, such as KV channel modulators.

  2. Fast Delayed Rectifier Potassium Current Required for Circadian Neural Activity

    PubMed Central

    JN, Itri; S, Michel; MJ, Vansteensel; JH, Meijer; CS, Colwell

    2005-01-01

    In mammals, the precise circadian timing of many biological processes depends on the generation of oscillations in neural activity of pacemaker cells in the suprachiasmatic nucleus (SCN). The ionic mechanisms underlying these rhythms are largely unknown. Using the mouse brain slice preparation, we demonstrate that the magnitude of fast delayed rectifier potassium currents exhibits a diurnal rhythm that peaks during the day. Importantly, this rhythm continues in constant darkness, providing the first demonstration of the circadian regulation of an intrinsic voltage–gated current in mammalian cells. Blocking this current prevented the daily rhythm in firing rate in SCN neurons. Kv3.1b and Kv3.2 potassium channels were found to be widely distributed within the SCN with higher expression during the day. We conclude that the fast delayed rectifier is necessary for the circadian modulation of electrical activity in SCN neurons, and represents an important part of the ionic basis for the generation of rhythmic output. PMID:15852012

  3. Potassium

    MedlinePlus

    ... the potassium you need. However, certain diseases (e.g., kidney disease and gastrointestinal disease with vomiting and ... substitute and to eat potassium-rich foods (e.g., bananas, prunes, raisins, and milk).

  4. Calcium-dependent potassium current in barnacle photoreceptor.

    PubMed

    Bolsover, S R

    1981-12-01

    When barnacle lateral eye photoreceptors are depolarized to membrane potentials of 0 to +50 mV in the dark, the plot of outward current through the cell membrane against time has two distinct maxima. The first maximum occurs 5-10 ms after the depolarization began. The current then decays to a minimum at approximately 500 ms after the onset of depolarization, and then increases to a second maximum 4-6 s after the depolarization began. If depolarization is maintained, the current again decays to reach a steady value approximately 1 min after depolarization began. The increase in current to the maximum at 4-6s from the minimum at approximately 500 ms is termed the "late current." It is maximum for depolarizations to around +25 mV and is reduced in amplitude at more positive potentials. It is not observed when the membrane is depolarized to potentials more positive than +60 mV. The late current is inhibited by external cobaltous ion and external tetraethylammonium ion, and shows a requirement for external calcium ion. When the calcium-sequestering agent EGTA is injected, the late current is abolished. Illumination of a cell under voltage clamp reduces the amplitude of the late current recorded subsequently in the dark. On the basis of the voltage dependence and pharmacology of the late current, it is proposed that the current is a calcium-dependent potassium current.

  5. KChIPs and Kv4 alpha subunits as integral components of A-type potassium channels in mammalian brain.

    PubMed

    Rhodes, Kenneth J; Carroll, Karen I; Sung, M Amy; Doliveira, Lisa C; Monaghan, Michael M; Burke, Sharon L; Strassle, Brian W; Buchwalder, Lynn; Menegola, Milena; Cao, Jie; An, W Frank; Trimmer, James S

    2004-09-08

    Voltage-gated potassium (Kv) channels from the Kv4, or Shal-related, gene family underlie a major component of the A-type potassium current in mammalian central neurons. We recently identified a family of calcium-binding proteins, termed KChIPs (Kv channel interacting proteins), that bind to the cytoplasmic N termini of Kv4 family alpha subunits and modulate their surface density, inactivation kinetics, and rate of recovery from inactivation (An et al., 2000). Here, we used single and double-label immunohistochemistry, together with circumscribed lesions and coimmunoprecipitation analyses, to examine the regional and subcellular distribution of KChIPs1-4 and Kv4 family alpha subunits in adult rat brain. Immunohistochemical staining using KChIP-specific monoclonal antibodies revealed that the KChIP polypeptides are concentrated in neuronal somata and dendrites where their cellular and subcellular distribution overlaps, in an isoform-specific manner, with that of Kv4.2 and Kv4.3. For example, immunoreactivity for KChIP1 and Kv4.3 is concentrated in the somata and dendrites of hippocampal, striatal, and neocortical interneurons. Immunoreactivity for KChIP2, KChIP4, and Kv4.2 is concentrated in the apical and basal dendrites of hippocampal and neocortical pyramidal cells. Double-label immunofluorescence labeling revealed that throughout the forebrain, KChIP2 and KChIP4 are frequently colocalized with Kv4.2, whereas in cortical, hippocampal, and striatal interneurons, KChIP1 is frequently colocalized with Kv4.3. Coimmunoprecipitation analyses confirmed that all KChIPs coassociate with Kv4 alpha subunits in brain membranes, indicating that KChIPs 1-4 are integral components of native A-type Kv channel complexes and are likely to play a major role as modulators of somatodendritic excitability.

  6. Segmental differences in firing properties and potassium currents in Drosophila larval motoneurons

    PubMed Central

    Srinivasan, Subhashini; Lance, Kimberley

    2012-01-01

    Potassium currents play key roles in regulating motoneuron activity, including functional specializations that are important for locomotion. The thoracic and abdominal segments in the Drosophila larval ganglion have repeated arrays of motoneurons that innervate body-wall muscles used for peristaltic movements during crawling. Although abdominal motoneurons and their muscle targets have been studied in detail, owing, in part, to their involvement in locomotion, little is known about the cellular properties of motoneurons in thoracic segments. The goal of this study was to compare firing properties among thoracic motoneurons and the potassium currents that influence them. Whole-cell, patch-clamp recordings performed from motoneurons in two thoracic and one abdominal segment revealed both transient and sustained voltage-activated K+ currents, each with Ca++-sensitive and Ca++-insensitive [A-type, voltage-dependent transient K+ current (IAv)] components. Segmental differences in the expression of voltage-activated K+ currents were observed. In addition, we demonstrate that Shal contributes to IAv currents in the motoneurons of the first thoracic segment. PMID:22157123

  7. Potassium currents in acutely isolated human hippocampal dentate granule cells.

    PubMed Central

    Beck, H; Clusmann, H; Kral, T; Schramm, J; Heinemann, U; Elger, C E

    1997-01-01

    1. Properties of voltage- and Ca(2+)-dependent K+ currents were investigated in thirty-four dentate granule cells acutely isolated from the resected hippocampus of eleven patients with therapy-refractory temporal lobe epilepsy (TLE). 2. When intracellular Ca2+ was strongly buffered with 11.5 mM EGTA-1 mM Ca2+ in the recording pipette, K+ currents (IK) with a slow activation and biexponential time-dependent decay could be elicited, which showed a threshold for activation around -30 mV. 3. A contribution of Ca(2+)-dependent K+ currents became apparent with intracellular solution containing 1 mM BAPTA-0.1 mM Ca2+. Superfusion of low-Ca2+ extracellular solution blocked 43% of outward currents in this recording configuration. Outward current components could also be blocked by substituting 5 mM Ba2+ for extracellular Ca2+ (78%), or by application of 100 microM Cd2+ (25%). 4. The Ca(2+)-dependent K+ currents could be pharmacologically subdivided into two components. One component was sensitive to 500 microM tetraethylammmonium (TEA; 41%) and 10 nM charybdotoxin (CTX; 47.2%). The blocking effects of 10 nM CTX and 500 microM TEA were not additive, suggesting that both agents block the same conductance. A second, smaller outward current component was blocked by 50 nM apamin (13%). 5. A transient A-type K+ current could be observed in six neurones and showed a fast monoexponential time-dependent inactivation with a steady-state voltage dependence that was distinct from that of IK. The A-type current was blocked by 4-aminopyridine (4-AP) but not by TEA or low-Ca2+ solution. 6. We conclude that outward currents in human hippocampal dentate granule cells can be separated into at least four types by their kinetic and pharmacological properties. These include at least one voltage-dependent current similar to those observed in mammalian hippocampal neurones, and two Ca(2+)-dependent K+ currents that most probably correspond to SK- and BK-type currents. A classical A-type current

  8. Allicin inhibits transient outward potassium currents in mouse ventricular myocytes.

    PubMed

    Cao, Hong; Huang, Congxin; Wang, Xin

    2016-05-01

    Allicin is the active constituent of garlic, a widely used spice and food. The remedial properties of garlic have also been extensively researched and it has been demonstrated that allicin is able to inhibit the transient outward potassium current (Ito) in atrial myocytes. However, the direct effect of allicin on Ito in ventricular myocytes has yet to be elucidated. In the present study, the effects of allicin on Ito in ventricular myocytes isolated from mice were investigated, using the whole-cell patch recording technique. The results revealed that Ito current was not significantly suppressed by allicin in the low-dose group (10 µmol/l; P>0.05). However, Ito was significantly inhibited by higher doses of allicin (30, 100 and 300 µmol/l; P<0.05 vs. control; n=6) in a concentration-dependent manner (IC50=41.6 µmol/l). In addition, a high concentration of allicin (≥100 µmol/l) was able to accelerate the voltage-dependent inactivation of Ito in mouse ventricular myocytes. In conclusion, the present study revealed that allicin inhibited the Ito in mouse ventricular myocytes, which may be the mechanism through which allicin exerts its antiarrhythmic effect.

  9. Allicin inhibits transient outward potassium currents in mouse ventricular myocytes

    PubMed Central

    CAO, HONG; HUANG, CONGXIN; WANG, XIN

    2016-01-01

    Allicin is the active constituent of garlic, a widely used spice and food. The remedial properties of garlic have also been extensively researched and it has been demonstrated that allicin is able to inhibit the transient outward potassium current (Ito) in atrial myocytes. However, the direct effect of allicin on Ito in ventricular myocytes has yet to be elucidated. In the present study, the effects of allicin on Ito in ventricular myocytes isolated from mice were investigated, using the whole-cell patch recording technique. The results revealed that Ito current was not significantly suppressed by allicin in the low-dose group (10 µmol/l; P>0.05). However, Ito was significantly inhibited by higher doses of allicin (30, 100 and 300 µmol/l; P<0.05 vs. control; n=6) in a concentration-dependent manner (IC50=41.6 µmol/l). In addition, a high concentration of allicin (≥100 µmol/l) was able to accelerate the voltage-dependent inactivation of Ito in mouse ventricular myocytes. In conclusion, the present study revealed that allicin inhibited the Ito in mouse ventricular myocytes, which may be the mechanism through which allicin exerts its antiarrhythmic effect. PMID:27168824

  10. Hormonal regulation of potassium currents in single myometrial cells.

    PubMed Central

    Toro, L; Stefani, E; Erulkar, S

    1990-01-01

    Three potassium currents (IK) were recorded from myometrial cells isolated from the uterus of rats at estrus and diestrus and kept in culture for 1-6 days. IK were differentiated by their modulation with norepinephrine and/or by their onset kinetics. At +50 mV the activation time constants were about 0.7 ms, 6 ms, and 15 ms for the fast, the intermediate, and the slow IK, respectively. Norepinephrine (1 microM) potentiated the fast IK and reduced the intermediate IK. In addition, differences were found with respect to cells from animals at estrus and diestrus. The fast IK was preferentially expressed in cultures from animals at estrus, whereas the intermediate IK was more frequent in cells from rats at diestrus. These results indicate that K+ channels from myometrial cells are multiregulated. Regulation may occur by short-term signals (neurotransmitters) and/or by preferentially expressing distinct types of channels depending on the hormonal status of the animal. PMID:2326254

  11. Inward rectifier potassium currents in mammalian skeletal muscle fibres.

    PubMed

    DiFranco, Marino; Yu, Carl; Quiñonez, Marbella; Vergara, Julio L

    2015-03-01

    Inward rectifying potassium (Kir) channels play a central role in maintaining the resting membrane potential of skeletal muscle fibres. Nevertheless their role has been poorly studied in mammalian muscles. Immunohistochemical and transgenic expression were used to assess the molecular identity and subcellular localization of Kir channel isoforms. We found that Kir2.1 and Kir2.2 channels were targeted to both the surface and the transverse tubular system membrane (TTS) compartments and that both isoforms can be overexpressed up to 3-fold 2 weeks after transfection. Inward rectifying currents (IKir) had the canonical features of quasi-instantaneous activation, strong inward rectification, depended on the external [K(+)], and could be blocked by Ba(2+) or Rb(+). In addition, IKir records show notable decays during large 100 ms hyperpolarizing pulses. Most of these properties were recapitulated by model simulations of the electrical properties of the muscle fibre as long as Kir channels were assumed to be present in the TTS. The model also simultaneously predicted the characteristics of membrane potential changes of the TTS, as reported optically by a fluorescent potentiometric dye. The activation of IKir by large hyperpolarizations resulted in significant attenuation of the optical signals with respect to the expectation for equal magnitude depolarizations; blocking IKir with Ba(2+) (or Rb(+)) eliminated this attenuation. The experimental data, including the kinetic properties of IKir and TTS voltage records, and the voltage dependence of peak IKir, while measured at widely dissimilar bulk [K(+)] (96 and 24 mm), were closely predicted by assuming Kir permeability (PKir) values of ∼5.5 × 10(-6 ) cm s(-1) and equal distribution of Kir channels at the surface and TTS membranes. The decay of IKir records and the simultaneous increase in TTS voltage changes were mostly explained by K(+) depletion from the TTS lumen. Most importantly, aside from allowing an accurate

  12. Inward rectifier potassium currents in mammalian skeletal muscle fibres

    PubMed Central

    DiFranco, Marino; Yu, Carl; Quiñonez, Marbella; Vergara, Julio L

    2015-01-01

    Inward rectifying potassium (Kir) channels play a central role in maintaining the resting membrane potential of skeletal muscle fibres. Nevertheless their role has been poorly studied in mammalian muscles. Immunohistochemical and transgenic expression were used to assess the molecular identity and subcellular localization of Kir channel isoforms. We found that Kir2.1 and Kir2.2 channels were targeted to both the surface andthe transverse tubular system membrane (TTS) compartments and that both isoforms can be overexpressed up to 3-fold 2 weeks after transfection. Inward rectifying currents (IKir) had the canonical features of quasi-instantaneous activation, strong inward rectification, depended on the external [K+], and could be blocked by Ba2+ or Rb+. In addition, IKir records show notable decays during large 100 ms hyperpolarizing pulses. Most of these properties were recapitulated by model simulations of the electrical properties of the muscle fibre as long as Kir channels were assumed to be present in the TTS. The model also simultaneously predicted the characteristics of membrane potential changes of the TTS, as reported optically by a fluorescent potentiometric dye. The activation of IKir by large hyperpolarizations resulted in significant attenuation of the optical signals with respect to the expectation for equal magnitude depolarizations; blocking IKir with Ba2+ (or Rb+) eliminated this attenuation. The experimental data, including the kinetic properties of IKir and TTS voltage records, and the voltage dependence of peak IKir, while measured at widely dissimilar bulk [K+] (96 and 24 mm), were closely predicted by assuming Kir permeability (PKir) values of ∼5.5 × 10−6 cm s−1 and equal distribution of Kir channels at the surface and TTS membranes. The decay of IKir records and the simultaneous increase in TTS voltage changes were mostly explained by K+ depletion from the TTS lumen. Most importantly, aside from allowing an accurate estimation of

  13. Nicotine inhibits potassium currents in Aplysia bag cell neurons.

    PubMed

    White, Sean H; Sturgeon, Raymond M; Magoski, Neil S

    2016-06-01

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

  14. Potassium currents in precursor cells isolated from the anterior subventricular zone of the neonatal rat forebrain.

    PubMed

    Stewart, R R; Zigova, T; Luskin, M B

    1999-01-01

    The progenitor cells from the anterior part of the neonatal subventricular zone, the SVZa, are unusual in that, although they undergo division, they have a neuronal phenotype. To characterize the electrophysiological properties of the SVZa precursor cells, recordings were made of potassium and sodium currents from SVZa cells that were removed from postnatal day 0-1 rats and cultured for 1 day. The properties of the delayed rectifier and A-type potassium currents were described by classical Hodgkin and Huxley analyses of activation and inactivation. In addition, cells were assessed under current clamp for their ability to generate action potentials. The A-type potassium current (IK(A)) was completely inactivated at a holding potential of -50 mV. The remaining potassium current resembled the delayed rectifier current (IK(DR)) in that it was blocked by tetraethylammonium (TEA; IC50 4.1 mM) and activated and inactivated slowly compared with IK(A). The conductance-voltage (G-V) curve revealed that G increased continuously from 0.2 nS at -40 mV to a peak of 2.6 nS at +10 or +20 mV, and then decreased for voltages above +30 mV. Activation time constants were largest at -40 mV ( approximately 11 ms) and smallest at 100 mV ( approximately 1.5 ms). The properties of IK(A) were studied in the presence of 20 mM TEA, to block IK(DR), and from a holding potential of -15 mV, to inactivate both IK(DR) and IK(A). IK(A) was then allowed to recover from inactivation to negative potentials during 200- to 800-ms pulses. Recovery from inactivation was fastest at -130 mV ( approximately 21 ms) and slowest at -90 mV ( approximately 135 ms). Inactivation was voltage independent from -60 to +60 mV with a time constant of approximately 15 ms. At steady state, IK(A) was half inactivated at -90 mV. GK(A) increased from 0.2 nS at -60 mV to a peak of 2.4 nS at +40 mV. Finally, the activation time constants ranged from approximately 1.9 ms at -50 mV to 0.7 ms at +60 mV. The properties of IK

  15. Two outward potassium current types are expressed during the neural differentiation of neural stem cells

    PubMed Central

    Bai, Ruiying; Gao, Guowei; Xing, Ying; Xue, Hong

    2013-01-01

    The electrophysiological properties of potassium ion channels are regarded as a basic index for determining the functional differentiation of neural stem cells. In this study, neural stem cells from the hippocampus of newborn rats were induced to differentiate with neurotrophic growth factor, and the electrophysiological properties of the voltage-gated potassium ion channels were observed. Immunofluorescence staining showed that the rapidly proliferating neural stem cells formed spheres in vitro that expressed high levels of nestin. The differentiated neurons were shown to express neuron-specific enolase. Flow cytometric analysis revealed that the neural stem cells were actively dividing and the percentage of cells in the S + G2/M phase was high. However, the ratio of cells in the S + G2/M phase decreased obviously as differentiation proceeded. Whole-cell patch-clamp recordings revealed apparent changes in potassium ion currents as the neurons differentiated. The potassium ion currents consisted of one transient outward potassium ion current and one delayed rectifier potassium ion current, which were blocked by 4-aminopyridine and tetraethylammonium, respectively. The experimental findings indicate that neural stem cells from newborn rat campus could be cultured and induced to differentiate into functional neurons under defined conditions in vitro. The differentiated neurons expressed two types of outward potassium ion currents similar to those of mature neurons in vivo. PMID:25206577

  16. Effects of external cesium and rubidium on outward potassium currents in squid axons.

    PubMed Central

    Clay, J R; Shlesinger, M F

    1983-01-01

    We have studied the effects of external cesium and rubidium on potassium conductance of voltage clamped squid axons over a broad range of concentrations of these ions relative to the external potassium concentration. Our primary novel finding concerning cesium is that relatively large concentrations of this ion are able to block a small, but statistically significant fraction of outward potassium current for potentials less than approximately 50 mV positive to reversal potential. This effect is relieved at more positive potentials. We have also found that external rubidium blocks outward current with a qualitatively similar voltage dependence. This effect is more readily apparent than the cesium blockade, occurring even for concentrations less than that of external potassium. Rubidium also has a blocking effect on inward current, which is relieved for potentials more than 20-40 mV negative to reversal, thereby allowing both potassium and rubidium ions to cross the membrane. We have described these results with a single-file diffusion model of ion permeation through potassium channels. The model analysis suggests that both rubidium and cesium ions exert their blocking effects at the innermost site of a two-site channel, and that rubidium competes with potassium ions for entry into the channel more effectively than does cesium under comparable conditions. PMID:6301576

  17. Evidence for a distinct light-induced calcium-dependent potassium current in Hermissenda crassicornis.

    PubMed

    Blackwell, K T

    2000-01-01

    A model of phototransduction is developed as a first step toward a model for investigating the critical interaction of light and turbulence stimuli within the type B photoreceptor of Hermissenda crassicronis. The model includes equations describing phototransduction, release of calcium from intracellular stores, and other calcium regulatory mechanisms, as well as equations describing ligand-gating of a rhabdomeric sodium current. The model is used to determine the sources of calcium in the soma, whether calcium or IP3 is a plausible ligand of the light-induced sodium current, and whether the light-induced potassium current is equivalent to the calcium-dependent potassium current activated by light-induced calcium release. Simulations show that the early light-induced calcium elevation is due to influx through voltage-dependent channels, whereas the later calcium elevation is due to release from intracellular stores. Simulations suggest that the ligand of the fast, light-induced sodium current is IP3 but that there is a smaller, prolonged component of the light-induced sodium current that is activated by calcium. In the model, the calcium-dependent potassium current, located in the soma, is activated only slightly by light-induced calcium elevation, leading to the prediction that a calcium-dependent potassium current, active at resting potential, is located in the rhabdomere and is responsible for the light-induced potassium current.

  18. Activation of protein kinase C inhibits potassium currents in cultured endothelial cells.

    PubMed

    Zhang, H; Weir, B; Daniel, E E

    1995-04-01

    The effect of protein kinase C on potassium channels in cultured endothelial cells was investigated by using whole-cell patch-clamp techniques. Activation of protein kinase C by phorbol 12-myristate 13-acetate (PMA) and phorbol 12,13-dibutyrate (PDBu), but not phorbol 12-monomyristate (PMM), an inactive analogue of phorbol esters, depressed an outward calcium-dependent potassium current. The inhibitory actions of PMA and PDBu could be reversed by the kinase inhibitor H-7. Cyclopiazonic acid, an inhibitor of the sarcoplasmic reticulum calcium pump, and LP-805, a novel vasodilator which also releases endothelium-derived relaxing factors, activated the outward calcium-dependent potassium conductance. PMA and PDBu, but not PMM, reduced the outward conductance induced by cyclopiazonic acid and LP-805. These effects of PMA and PDBu on potassium currents may be mediated either by phosphorylation of ion channels, or by decreasing intracellular calcium concentration.

  19. Cloning of a Membrane Protein that Induces a Slow Voltage-Gated Potassium Current

    NASA Astrophysics Data System (ADS)

    Takumi, Toru; Ohkubo, Hiroaki; Nakanishi, Shigetada

    1988-11-01

    A rat kidney messenger RNA that induces a slowly activating, voltage-dependent potassium current on its expression in Xenopus oocytes was identified by combining molecular cloning with an electrophysiological assay. The cloned complementary DNA encodes a novel membrane protein that consists of 130 amino acids with a single putative transmembrane domain. This protein differs from the known ion channel proteins but is involved in the induction of selective permeation of potassium ions by membrane depolarization.

  20. Potassium currents in isolated CA1 neurons of the rat after kindling epileptogenesis.

    PubMed

    Vreugdenhil, M; Wadman, W J

    1995-06-01

    Daily tetanic stimulation of the Schaffer collaterals generates an epileptogenic focus in area CA1 of the rat hippocampus, ultimately leading to generalized tonic-clonic convulsions (kindling). Potassium currents were measured under voltage-clamp conditions in pyramidal neurons, acutely dissociated from the focus of fully kindled rats, one day and six weeks after the last generalized seizure. Their amplitude, kinetics, voltage dependence and calcium dependence were compared with controls. With Ca2+ influx blocked by 0.5 mM Ni2+, the sustained current (delayed rectifier) and the transient current (A-current) were not different after kindling. Calcium influx evoked an additional fast transient current component. This transient calcium-dependent current component was increased by 154%, but only immediately after the seizure. A second, slow calcium-dependent potassium current component was dependent on the intracellular calcium level, set by the pipette as well as on calcium influx. The peak amplitude of this slow calcium-dependent current was under optimal calcium conditions not different after kindling, but we found indications that either calcium homeostasis or the calcium sensitivity of the potassium channels was affected by the kindling process. In contrast to the previously described enhancement of calcium current, kindling epileptogenesis did not change the total potassium current amplitude. The minor changes that were observed can be related either to changes in calcium current or to changes in intracellular calcium homeostasis.

  1. Expression of voltage dependent potassium currents in freshly dissociated rat articular chondrocytes.

    PubMed

    Ponce, Arturo

    2006-01-01

    The electrophysiological properties of voltage dependent potassium channels from freshly dissociated rat articular chondrocytes were studied. The resting membrane potential (-42.7+/-2.0 mV) was significantly depolarized by increasing concentrations of external potassium. No change was observed when external chloride concentration was varied. Addition of TEA, 4AP, alpha-Dendrotoxin and charybdotoxin depolarized resting membrane potential. Whole cell patch clamp studies revealed the presence of outwardly rectifying currents whose kinetic and pharmacological properties suggest the expression of voltage dependent potassium channels. Two kinds of currents were observed under the same experimental conditions. The first one, most frequently observed (80%), starts activating near -50 mV, with V(1/2)=-18 mV, G(max)=0.30 pS/pF. The second kind was observed in only 10% of cases; It activates near -40 mV, with(1/2)=+28.35 mV, G(max)=0.28 pS/pF pA/pF and does not inactivates. Inactivating currents were significantly inhibited by TEA (IC(50)=1.45 mM), 4AP (IC(50)=0.64 mM), CTX (IC(50) = 10 nM), alpha-Dendrotoxin (IC(50) < 100 nM) and Margatoxin (IC(50)=28.5 nM). These results show that rat chondrocytes express voltage dependent potassium currents and suggest a role of voltage-dependent potassium channels in regulating membrane potential of rat chondrocytes.

  2. Histamine Enhances Voltage-Gated Potassium Currents of ON Bipolar Cells in Macaque Retina

    PubMed Central

    Yu, Yong-Chun; Satoh, Hiromasa; Wu, Samuel M.; Marshak, David W.

    2012-01-01

    Purpose The goal was to understand the functions of retinopetal axons containing histamine. In prior work, type 3 histamine receptors (HR3) have been localized to the tips of ON bipolar cell dendrites in macaque retinas. Voltage-gated potassium channels have also been localized to bipolar cell dendrites, and the hypothesis tested in the present study was that these are modulated by histamine. Methods Whole-cell recordings of potassium currents were made from bipolar cells in slice preparations of macaque retina. In voltage-clamp mode, the cells were held at −60 mV and stepped to values from −60 to 80 mV. Recordings of the membrane potential were also made in current-clamp mode. Histamine, the HR3 agonist (R) α-methylhistamine (RAMH), tetraethyl ammonium (TEA), and 4-aminopyridine (4-AP) were applied in the superfusate. Results Histamine produced a dose-dependent increase in potassium currents in a subset of bipolar cells. At 5 μM, histamine increased the currents by 15% or more in the ON bipolar cells but not in the OFF bipolar cells. RAMH at 5 μM increased the amplitude of the potassium currents in the ON bipolar cells. In 10 mM TEA, potassium currents were reduced in all the bipolar cells, and there was no effect of histamine. Histamine hyperpolarized the resting membrane potential of the ON bipolar cells by 5 mV. Conclusions By enhancing potassium currents in the ON bipolar cells, histamine is expected to reduce the amplitude of the light responses and limit their duration. The hyperpolarization of the resting membrane potential would also reduce neurotransmitter release at their output synapses. PMID:18836167

  3. Voltage-dependent potassium currents in cochlear hair cells of the embryonic chick.

    PubMed

    Griguer, C; Fuchs, P A

    1996-01-01

    1. Hair cells were isolated from apical and basal regions of the embryonic chick's cochlea. Outward potassium currents were recorded using whole cell tight-seal voltage clamp. 2. Outward currents in basal hair cells activated and inactivated rapidly. The average time to half-maximum at 0 mV was 2.9 ms. The time constant of inactivation at 0 mV was 71 ms. Boltzmann fits to conductance-voltage curves gave an average half-activation voltage of -36 mV, and steady-state inactivation was half-maximal at -62 mV. 3. Potassium currents in apical hair cells had slower kinetics, with a time to half-maximum of 6.7 ms and an inactivation time constant of 242 ms at + 10 mV. The half-activation voltage derived from Boltzmann fits was -16 mV and that for inactivation was -43 mV. 4. With respect to kinetic and voltage-dependent properties, the rapidly and slowly activating potassium currents of embryonic cells were similar to the rapidly inactivating "A" current of mature short hair cells and to the delayed rectifier of mature tall hair cells. However, unlike the adult currents, the embryonic currents did not show differential sensitivities to tetraethylammonium chloride and 4-aminopyridine. As early as the tenth day of embryogenesis, hair cells at the apical and basal extremes of the cochlea produced functionally distinct voltage-gated potassium currents.

  4. Muscarinic agonists and potassium currents in guinea-pig myenteric neurones.

    PubMed

    Galligan, J J; North, R A; Tokimasa, T

    1989-01-01

    1. Intracellular electrophysiological recordings were obtained from single neurones of the guinea-pig myenteric plexus in vitro. Using single electrode voltage clamp techniques, four distinct potassium currents were described and the effects of muscarinic agonists on these currents were studied. 2. A calcium-dependent potassium current (gKCa) was present in AH neurones at rest, and was much increased following a brief depolarization (50 ms, to 0 mV). Muscarinic agonists reduced both the resting current and the current evoked by depolarization. Pirenzepine competitively antagonized the suppression by muscarine of the calcium-dependent potassium current (or after-hyperpolarization) following an action potential. The dissociation equilibrium constant for pirenzepine was about 10 nM. 3. The conductance of AH neurones increased two to three fold when they were hyperpolarized negative to -90 mV. This inward rectification was blocked by extracellular caesium (2 mM) or rubidium (2 mM), but not by tetraethylammonium (TEA, 40 mM), 4-aminopyridine (100 microM) or cobalt (2 mM). The inward rectification was unaffected by muscarinic agonists. 4. When AH neurones were depolarized from very negative holding potentials (less than -80 mV) a brief outward current was recorded with a duration of about 200 ms. This transient or A current was completely blocked by 4-aminopyridine (100 microM) but was not affected by tetrodotoxin (300 nM), TEA (40 mM) or cobalt (2 mM). Muscarinic agonists did not affect the A current. 5. In S neurones, and in AH neurones in calcium-free solutions, the potassium conductance (in TEA and caesium) behaved according to constant field assumptions. This background conductance was suppressed by muscarinic agonists. 6. It is concluded that the depolarization by muscarinic agonists of myenteric AH neurones is due to a suppression of both a calcium-dependent potassium conductance and a background potassium conductance. Muscarinic depolarization of S neurones

  5. Dynamics and diversity in interneurons: a model exploration with slowly inactivating potassium currents.

    PubMed

    Saraga, F; Skinner, F K

    2002-01-01

    Recent experimental and model work indicates that slowly inactivating potassium currents might play critical roles in generating population rhythms. In particular, slow (<1-4 Hz) rhythms recorded in the hippocampus correlate with oscillatory behaviors in interneurons in this frequency range. Limiting the ion channels to the traditional Hodgkin-Huxley sodium and potassium currents, a persistent sodium current, and a slowly inactivating potassium current, we explore the role of slowly inactivating conductances in a multi-compartmental interneuronal model. We find a rich repertoire of tonic and bursting behaviors depending on the distribution, density and kinetics of this conductance. Specifically, burst frequencies of appropriate frequencies could be obtained for certain distributions and kinetics of this conductance. Robust (with respect to injected currents) regimes of tonic firing and bursting behaviors are uncovered. In addition, we find a bistable tonic firing pattern that depends on the slowly inactivating potassium current. Therefore, this work shows ways in which different channel distributions and heterogeneities could produce variable signal outputs. We suggest that an understanding of the dynamical profiles of inhibitory neurons based on the density and distribution of their currents is helpful in dissecting out the complex roles played by this heterogeneous group of cells.

  6. Properties of calcium and potassium currents of clonal adrenocortical cells

    PubMed Central

    1989-01-01

    The ionic currents of clonal Y-1 adrenocortical cells were studied using the whole-cell variant of the patch-clamp technique. These cells had two major current components: a large outward current carried by K ions, and a small inward Ca current. The Ca current depended on the activity of two populations of Ca channels, slow (SD) and fast (FD) deactivating, that could be separated by their different closing time constants (at -80 mV, SD, 3.8 ms, and FD, 0.13 ms). These two kinds of channels also differed in (a) activation threshold (SD, approximately - 50 mV; FD, approximately -20 mV), (b) half-maximal activation (SD, between -15 and -10 mV; FD between +10 and +15 mV), and (c) inactivation time course (SD, fast; FD, slow). The total amplitude of the Ca current and the proportion of SD and FD channels varied from cell to cell. The amplitude of the K current was strongly dependent on the internal [Ca2+] and was almost abolished when internal [Ca2+] was less than 0.001 microM. The K current appeared to be independent, or only slightly dependent, of Ca influx. With an internal [Ca2+] of 0.1 microM, the activation threshold was -20 mV, and at +40 mV the half- time of activation was 9 ms. With 73 mM external K the closing time constant at -70 mV was approximately 3 ms. The outward current was also modulated by internal pH and Mg. At a constant pCa gamma a decrease of pH reduced the current amplitude, whereas the activation kinetics were not much altered. Removal of internal Mg produced a drastic decrease in the amplitude of the Ca-activated K current. It was also found that with internal [Ca2+] over 0.1 microM the K current underwent a time- dependent transformation characterized by a large increase in amplitude and in activation kinetics. PMID:2539432

  7. The properties and distribution of inward rectifier potassium currents in pig coronary arterial smooth muscle.

    PubMed Central

    Quayle, J M; Dart, C; Standen, N B

    1996-01-01

    1. Whole-cell potassium currents were studied in single smooth muscle cells enzymatically isolated from pig coronary arteries. 2. In cells isolated from small diameter branches of the left anterior descending coronary artery (LAD), an inward rectifier potassium current (IK(IR)) was identified, which was inhibited by extracellular barium ions, suggesting the presence of inward rectifier potassium (KIR) channels. 3. The conductance for IK(IR) measured in 6, 12, 60 and 140 mM extracellular potassium was a function of membrane potential and the extracellular potassium concentration. 4. On hyperpolarization, IK(IR) activated along an exponential time course with a time constant that was voltage dependent. 5. Inward rectifier current was compared in cells isolated from coronary vessels taken from different points along the vascular tree. Current density was greater in cells isolated from small diameter coronary arteries; at -140 mV it was -20.5 +/- 4.4 pA pF-1 (n = 23) in 4th order branches of the LAD, but -0.8 +/- 0.2 pA pF-1 (n = 11) in the LAD itself. 6. In contrast to IK(IR), there was little effect of arterial diameter on the density of voltage-dependent potassium current; densities at +30 mV were 12.8 +/- 1.3 pA pF-1 (n = 19) in 4th order branches and 17.4 +/- 3.1 pA pF-1 (n = 11) in the LAD. 7. We conclude that KIR channels are present in pig coronary arteries, and that they are expressed at a higher density in small diameter arteries. The presence of an enhanced IK(IR) may have functional consequences for the regulation of cell membrane potential and tone in small coronary arteries. PMID:8865069

  8. The kinetics and rectifier properties of the slow potassium current in cardiac Purkinje fibres

    PubMed Central

    Noble, D.; Tsien, R. W.

    1968-01-01

    1. The reversal potential of the slow outward current in Purkinje fibres varies with [K]o in accordance with the expected potassium equilibrium potential. It is concluded that virtually all of this current is carried by potassium ions. 2. The magnitude of the current is determined by two separable factors. The first factor is directly proportional to a variable obeying first-order voltage-dependent kinetics of the Hodgkin—Huxley type but with extremely long time constants. The time constants of this variable are extremely sensitive to temperature and the Q10 over the range 26-38° C is 6. 3. The second factor shows inward-going rectification with a marked negative slope in the current—voltage relation beyond about 25 mV positive to the K equilibrium potential. The current—voltage relations measured at different values of [K]o cross each other on the outward current side of the equilibrium potential. 4. The changes in slow potassium current during pace-maker activity have been calculated. It is shown that the mechanism of the pace-maker potential differs in several important respects from that described by Noble's (1962) model. The negative slope in the current—voltage relation appears to be an important factor in generating the last phase of pace-maker depolarization. 5. The role of the slow potassium current during the action potential and the consequences of the high temperature dependence of the kinetics are discussed. PMID:5639799

  9. Calcium activates and inactivates a photoreceptor soma potassium current.

    PubMed Central

    Alkon, D L; Sakakibara, M

    1985-01-01

    Light-induced currents were measured with a two-microelectrode voltage clamp of type B photoreceptor somata, which had been isolated by axotomy from all synaptic interactions as well as from all membranes capable of generating impulse activity. In artificial seawater (ASW), light elicited a transient early inward current, INa+, which depended on Na+o and had a linear current-voltage relation and an extrapolated reversal potential of 30-40 mV (absolute). In 0-Na+ ASW, light elicited a transient short-latency outward current that dependent on K+o, increased exponentially with more positive voltages (greater than or equal to -40 mV), and reversed at -70 to -75 mV. This outward current was not blocked by Ca++ channel blockers (e.g., Cd++, Co++) or substitution of Ba++o, for Ca++o, but was reduced by iontophoretic injection of EGTA. In both ASW and 0-Na+ ASW, light also elicited a delayed, apparently inward current, which was associated with a decreased conductance, depended on K+o, increased exponentially with more positive voltages (greater than or equal to -40 mV), reversed at the equilibrium potential for K+ flux in elevated K+o was eliminated by substitution of Ba++o for Ca++o, and was greatly reduced by Cd++o or Co++o. Thus, light elicited an early Ca++-dependent K+ current, IC, and a prolonged decrease of IC. Iontophoretic injection of Ca++ through a third microelectrode caused prolonged reduction of both IC and the light-induced decrease of IC, but did not alter ICa++ or the current-voltage relation of IC. Ruthenium red (1 microM) in the external medium caused a prolongation of the light-induced decrease of IC. Iontophoretic injection of EGTA often eliminated the light-induced IC decrease while decreasing peak IC (during depolarizing steps to -5 or 0 mV) by less than one-half. EGTA injection, on the average, did not affect steady state IC but reduced the light-induced decrease of steady state IC to approximately one-third of its original magnitude. The prolonged

  10. Aminopyridines block an inactivating potassium current having slow recovery kinetics.

    PubMed Central

    Wagoner, P K; Oxford, G S

    1990-01-01

    The blocking action of aminopyridines on an inactivating K current (lKi) in GH3 pituitary cells was studied before and after altering the macroscopic decay of the current with N-bromoacetamide (NBA). The first depolarizing pulse delivered either seconds or minutes after beginning 4-aminopyridine (4AP) application, elicited a current with both a more rapid decay and a reduced peak amplitude. The rapid decay (or time-dependent block) was especially prominent in NBA-treated cells. With continued drug application, subsequent test pulses revealed a stable block of peak current, greater in NBA-treated than control cells. Recovery from block was enhanced by hyperpolarizing holding potentials and by the first depolarizing pulse delivered after prolonged recovery intervals. Unlike aminopyridine block of other K currents, there was no convincing evidence for voltage shifts in activation or inactivation, or for voltage and frequency-dependent unblock. Increasing the open probability of the channels did, however, facilitate the block. Although the behavior of currents in 4AP was suggestive of "open channel block," the block was not produced by 4-aminopyridine methiodide, a positively charged aminopyridine. Moreover, because partial block and recovery occurred without opening the channels we suggest that aminopyridines bind to, or near, this K channel, that this binding is enhanced by opening the channel, and that a conformational change is induced which mimics inactivation. Because recovery from block is enhanced by negative potentials, we suggest that aminopyridine molecules may become "trapped" by inactivation awaiting the slow process of reactivation to escape their binding sites. PMID:2275964

  11. Potassium currents in type II vestibular hair cells isolated from the guinea-pig's crista ampullaris.

    PubMed

    Griguer, C; Kros, C J; Sans, A; Lehouelleur, J

    1993-11-01

    Type II vestibular hair cells were isolated from cristae ampullares of guinea-pig and maintained in vitro for 2-3 h. Outward membrane currents were studied under whole-cell voltage-clamp conditions. Type II hair cells had resting potentials of about -45 mV. Depolarizing voltage steps from a holding potential of -80 or -90 mV induced time- and voltage-dependent outward currents which slowly decayed to a sustained level. Tail currents reversed at about -70 mV, indicating that the outward currents were mainly carried by potassium ions. The currents had an activation threshold around -50 mV. The transient component was completely removed by a depolarizing pre-pulse positive to -10 mV. While bath application of 4-aminopyridine (5 mM) reduced both components, extracellular tetraethylammonium (10 mM) or zero calcium preferentially diminished the sustained current. We conclude that at least two potassium conductances are present, a delayed rectifier with a relatively fast inactivation and a calcium-dependent potassium current. Depolarizing current injections induced an electrical resonance in the voltage responses, with a frequency of 25-100 Hz, larger currents causing higher frequencies.

  12. Potassium currents in auditory hair cells of the frog basilar papilla.

    PubMed

    Smotherman, M S; Narins, P M

    1999-06-01

    The whole-cell patch-clamp technique was used to identify and characterize ionic currents in isolated hair cells of the leopard frog basilar papilla (BP). This end organ is responsible for encoding the upper limits of a frog's spectral sensitivity (1.25-2.0 kHz in the leopard frog). Isolated BP hair cells are the smallest hair cells in the frog auditory system, with spherical cell bodies typically less than 20 microm in diameter and exhibiting whole-cell capacitances of 4-7 pF. Hair cell zero-current resting potentials (Vz) varied around a mean of -65 mV. All hair cells possessed a non-inactivating, voltage-dependent calcium current (I(Ca)) that activates above a threshold of -55 mV. Similarly all hair cells possessed a rapidly activating, outward, calcium-dependent potassium current (I(K)(Ca)). Most hair cells also possessed a slowly activating, outward, voltage-dependent potassium current (I(K)), which is approximately 80% inactive at the hair cell Vz, and a fast-activating, inward-rectifying potassium current (I(K1)) which actively contributes to setting Vz. In a small subset of cells I(K) was replaced by a fast-inactivating, voltage-dependent potassium current (I(A)), which strongly resembled the A-current observed in hair cells of the frog sacculus and amphibian papilla. Most cells have very similar ionic currents, suggesting that the BP consists largely of one homogeneous population of hair cells. The kinetic properties of the ionic currents present (in particular the very slow I(K)) argue against electrical tuning, a specialized spectral filtering mechanism reported in the hair cells of birds, reptiles, and amphibians, as a contributor to frequency selectivity of this organ. Instead BP hair cells reflect a generalized strategy for the encoding of high-frequency auditory information in a primitive, mechanically tuned, terrestrial vertebrate auditory organ.

  13. Adiponectin modulates excitability of rat paraventricular nucleus neurons by differential modulation of potassium currents.

    PubMed

    Hoyda, Ted D; Ferguson, Alastair V

    2010-07-01

    The adipocyte-derived hormone adiponectin acts at two seven-transmembrane domain receptors, adiponectin receptor 1 and adiponectin receptor 2, present in the paraventricular nucleus of the hypothalamus to regulate neuronal excitability and endocrine function. Adiponectin depolarizes rat parvocellular preautonomic neurons that secrete either thyrotropin releasing hormone or oxytocin and parvocellular neuroendocrine corticotropin releasing hormone neurons, leading to an increase in plasma adrenocorticotropin hormone concentrations while also hyperpolarizing a subgroup of neurons. In the present study, we investigate the ionic mechanisms responsible for these changes in excitability in parvocellular paraventricular nucleus neurons. Patch clamp recordings of currents elicited from slow voltage ramps and voltage steps indicate that adiponectin inhibits noninactivating delayed rectifier potassium current (I(K)) in a majority of neurons. This inhibition produced a broadening of the action potential in cells that depolarized in the presence of adiponectin. The depolarizing effects of adiponectin were abolished in cells pretreated with tetraethyl ammonium (0/15 cells depolarize). Slow voltage ramps performed during adiponectin-induced hyperpolarization indicate the activation of voltage-independent potassium current. These hyperpolarizing responses were abolished in the presence of glibenclamide [an ATP-sensitive potassium (K(ATP)) channel blocker] (0/12 cells hyperpolarize). The results presented in this study suggest that adiponectin controls neuronal excitability through the modulation of different potassium conductances, effects which contribute to changes in excitability and action potential profiles responsible for peptidergic release into the circulation.

  14. Age-dependent variations in potassium sensitivity of A-currents in rat hippocampal neurons.

    PubMed

    Klee, R; Eder, C; Ficker, E; Heinemann, U

    1997-09-01

    Hippocampal pyramidal neurons were either cultured from prenatal rats or acutely isolated from the brain of newborn and juvenile rats. The influence of lowering the concentration of the extracellular potassium concentration ([K+]o) on isolated fast transient outward K+ currents (I(A)) was studied in these neurons using the patch clamp technique in the whole cell configuration. With respect to the response of I(A) to lowering [K+]o, three types of cells were observed. The first subpopulation of neurons was characterized by a complete suppression of I(A) over the whole voltage range under potassium-free solutions (type A neurons). A second proportion of cells showed an increase of I(A) at test pulses below -0 mV and a decrease of I(A) at voltages above -0 mV (type B neurons). In a third group of neurons, amplitudes of I(A) increased at all potentials tested during omission of potassium ions from the extracellular superfusate (type C neurons). Whereas type A and type B neurons were preferentially found in freshly plated cultures and newborn rats, the majority of type C cells was detected in long-term cultures and in animals of older ages. Thus, hippocampal A-currents lose their sensitivity to extracellular potassium ions during early ontogenesis.

  15. Two transient potassium currents in layer V pyramidal neurones from cat sensorimotor cortex.

    PubMed Central

    Spain, W J; Schwindt, P C; Crill, W E

    1991-01-01

    1. Two transient outward currents were identified in large pyramidal neurones from layer V of cat sensorimotor cortex ('Betz cells') using an in vitro brain slice preparation and single-microelectrode voltage clamp. Properties of the currents deduced from voltage-clamp measurements were reflected in neuronal responses during constant current stimulation. 2. Both transient outward currents rose rapidly after a step depolarization, but their subsequent time course differed greatly. The fast-transient current decayed within 20 ms, while the slow-transient current took greater than 10 s to decay. Raised extracellular potassium reduced current amplitude. Both currents were present in cadmium-containing or calcium-free perfusate. 3. Tetraethylammonium had little effect on the slow-transient current at a concentration of 1 mM, but the fast-transient current was reduced by 60%. 4-Aminopyridine had little effect on the fast-transient current over the range 20 microM-2 mM, but these concentrations reduced the slow-transient current and altered its time course. 4. Both transient currents were evoked by depolarizations below action potential threshold. The fast-transient current was evoked by a 7 mV smaller depolarization than the slow-transient current, but its chord conductance increased less steeply with depolarization. 5. Voltage-dependent inactivation of the fast-transient was steeper than that of the slow-transient current (4 vs. 7 mV per e-fold change), and half-inactivation occurred at a less negative potential (-59 vs. -65 mV). The activation and inactivation characteristics of each current overlapped, however, implying the existence of a steady 'window current' extending over a range of approximately 14 mV beginning negative to action potential threshold. 6. The fast-transient current displayed a clear voltage dependence of both its activation and inactivation kinetics, whereas the slow-transient current did not. Recovery of either current from inactivation took

  16. Development of voltage-dependent calcium, sodium, and potassium currents in Xenopus spinal neurons.

    PubMed

    O'Dowd, D K; Ribera, A B; Spitzer, N C

    1988-03-01

    Action potentials of embryonic nerve and muscle cells often have a different ionic dependence and longer duration than those of mature cells. The action potential of spinal cord neurons from Xenopus laevis exhibits a prominent calcium component at early stages of development that diminishes with age as the impulse becomes principally sodium dependent. Whole-cell voltage-clamp analysis has been undertaken to characterize the changes in membrane currents during development of these neurons in culture. Four voltage-dependent currents of cells were identified and examined during the first day in vitro, when most of the change in the action potential occurs. There are no changes in the peak density of the calcium current (ICa), its voltage dependence, or time to half-maximal activation; a small increase in inactivation is apparent. The major change in sodium current (INa) is a 2-fold increase in its density. In addition, more subtle changes in the kinetics of the macroscopic sodium current were noted. The peak density of voltage-dependent potassium current (IKv) increases 3-fold, and this current becomes activated almost twice as fast. No changes were noted in the extent of its inactivation. The calcium-dependent potassium current (IKc) consists of an inactivating and a sustained component. The former increases 2-fold in peak current density, and the latter increases similarly at less depolarized voltages. The changes in these currents contribute to the decrease in duration and the change in ionic dependence of the impulse.

  17. Voltage-dependent calcium and calcium-activated potassium currents of a molluscan photoreceptor.

    PubMed

    Alkon, D L; Farley, J; Sakakibara, M; Hay, B

    1984-11-01

    Two-microelectrode voltage clamp studies were performed on the somata of Hermissenda Type B photoreceptors that had been isolated by axotomy from all synaptic interaction as well as any impulse-generating (i.e., active) membrane. In the presence of 2-10 mM 4-aminopyridine (4-AP) and 100 mM tetraethylammonium ion (TEA), which eliminated two previously described voltage-dependent potassium currents (IA and the delayed rectifier), a voltage-dependent outward current was apparent in the steady state responses to command voltage steps more positive than -40 mV (absolute). This current increased with increasing external Ca++. The magnitude of the outward current decreased and an inward current became apparent following EGTA injection. Substitution of external Ba++ for Ca++ also made the inward current more apparent. This inward current, which was almost eliminated after being exposed for approximately 5 min to a solution in which external Ca++ was replaced with Cd++, was maximally activated at approximately 0 mV. Elevation of external potassium allowed the calcium (ICa++) and calcium-dependent K+ (IC) currents to be substantially separated. Command pulses to 0 mV elicited maximal ICa++ but no IC because no K+ currents flowed at their new reversal potential (0 mV) in 300 mM K+. At a holding potential of -60 mV, which was now more negative than the potassium equilibrium potential, EK+, in 300 mM K+, IC appeared as an inward tail current after positive command steps. The voltage dependence of ICa++ was demonstrated with positive steps in 100 mM Ba++, 4-AP, and TEA. Other data indicated that in 10 mM Ca++, IC underwent pronounced and prolonged inactivation whereas ICa++ did not. When the photoreceptor was stimulated with a light step (with the membrane potential held at -60 mV), there was also a prolonged inactivation of IC. In elevated external Ca++, ICa++ also showed similar inactivation. These data suggest that IC may undergo prolonged inactivation due to a direct effect

  18. Voltage-dependent calcium and calcium-activated potassium currents of a molluscan photoreceptor.

    PubMed Central

    Alkon, D L; Farley, J; Sakakibara, M; Hay, B

    1984-01-01

    Two-microelectrode voltage clamp studies were performed on the somata of Hermissenda Type B photoreceptors that had been isolated by axotomy from all synaptic interaction as well as any impulse-generating (i.e., active) membrane. In the presence of 2-10 mM 4-aminopyridine (4-AP) and 100 mM tetraethylammonium ion (TEA), which eliminated two previously described voltage-dependent potassium currents (IA and the delayed rectifier), a voltage-dependent outward current was apparent in the steady state responses to command voltage steps more positive than -40 mV (absolute). This current increased with increasing external Ca++. The magnitude of the outward current decreased and an inward current became apparent following EGTA injection. Substitution of external Ba++ for Ca++ also made the inward current more apparent. This inward current, which was almost eliminated after being exposed for approximately 5 min to a solution in which external Ca++ was replaced with Cd++, was maximally activated at approximately 0 mV. Elevation of external potassium allowed the calcium (ICa++) and calcium-dependent K+ (IC) currents to be substantially separated. Command pulses to 0 mV elicited maximal ICa++ but no IC because no K+ currents flowed at their new reversal potential (0 mV) in 300 mM K+. At a holding potential of -60 mV, which was now more negative than the potassium equilibrium potential, EK+, in 300 mM K+, IC appeared as an inward tail current after positive command steps. The voltage dependence of ICa++ was demonstrated with positive steps in 100 mM Ba++, 4-AP, and TEA. Other data indicated that in 10 mM Ca++, IC underwent pronounced and prolonged inactivation whereas ICa++ did not. When the photoreceptor was stimulated with a light step (with the membrane potential held at -60 mV), there was also a prolonged inactivation of IC. In elevated external Ca++, ICa++ also showed similar inactivation. These data suggest that IC may undergo prolonged inactivation due to a direct effect

  19. Inhibition of potassium currents is involved in antiarrhythmic effect of moderate ethanol on atrial fibrillation.

    PubMed

    Yang, Baode; Li, Chenxing; Sun, Junyi; Wang, Xinghui; Liu, Xinling; Yang, Chun; Chen, Lina; Zhou, Jun; Hu, Hao

    2017-03-08

    Excessive consumption of alcohol is a well-established risk factor of atrial fibrillation (AF). However, the effects of moderate alcohol drinking remain to be elucidated. This study was designed to determine the effects of moderate ethanol ingestion on atrial fibrillation and the electrophysiological mechanisms. In acetylcholine-induced canine and mouse AF models, the moderate ethanol prevented the generation and persistence of AF through prolonging the latent period of AF and shortening the duration of AF. The action potential duration (APD) was remarkably prolonged under the concentration range of 12.5-50.0mM ethanol in guinea pig atrial myocytes. Ultra-rapid delayed rectified potassium currents (IKv1.5) were markedly inhibited by 12.5-50.0mM ethanol in a concentration-dependent manner. Ethanol with 50.0mM could inhibit rapid delayed rectifier potassium currents (IhERG). Ethanol under 6.25-50.0mM did not affect on inward rectifier potassium currents (IKir2.1). Collectively, the present study provided an evidence that moderate ethanol intake can prolong the APD of atrial myocytes by inhibition of IKv1.5 and IhERG, which contributed to preventing the development and duration of AF.

  20. Cholesterol influences potassium currents in inner hair cells isolated from guinea pig cochlea.

    PubMed

    Kimitsuki, Takashi

    2017-02-01

    There is a correlation between serum hyperlipidemia and hearing loss. Cholesterol is an integral component of the cell membrane and regulates the activity of ion channels in the lipid bilayer. The aim of this study was to investigate the effects of cholesterol on the potassium currents in IHCs by using the cholesterol-depleting drug, MβCD, and water-soluble cholesterol. IHCs were acutely isolated from a mature guinea-pig cochlea and potassium currents were recorded. MβCD and water-soluble cholesterol were applied to IHCs under pressure puff pipettes. IHCs showed outwardly rectifying currents (IK,f and IK,s) in response to depolarizing voltage pulses, with only a slight inward current (IK,n) when hyperpolarized. In 10mM MβCD solutions, the amplitude of outward K currents reversely decreased; however, fast activation kinetics was preserved. In contrast, in solution of 1mM water-soluble cholesterol, the amplitude of outward K currents reversely increased. At the membrane potential of +110mV, relative conductances were 0.87±0.07 and 1.18±0.11 in MβCD solutions and cholesterol solutions, respectively. The amplitude of K currents in isolated IHCs was reversely changed by cholesterol-depleting drug and water-soluble cholesterol. These results demonstrated the possibility of the involvement of IHC function in hyperlipidemia-induced inner ear disorders. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. N-(4-pyridyl) methyl carbamate inhibits fast potassium currents in guinea pig dorsal root ganglion cells.

    PubMed

    Sun, Wenjing; Smith, Daniel; Bryn, Steven; Borgens, Richard; Shi, Riyi

    2009-02-15

    Axonal demyelination is a critical pathological phenomenon associated with spinal cord injury and multiple sclerosis (MS). Previous studies demonstrated that 4-Aminopyridine, a fast potassium channel blocker, enhances impulse conduction on damaged and/or demyelinated axons, allowing for functional recovery in spinal cord injuries and MS, but with severe therapeutic limitations. To continue to explore the therapeutic value of blocking fast potassium channels while circumventing the side effects of 4-AP, we have developed three novel 4-AP derivatives that enhance impulse conduction in spinal cord trauma. In the current study, we have shown that one of these three derivatives, N-(4-pyridyl) methyl carbamates (MC), significantly inhibits a fast, I(A) like potassium current in guinea pig dorsal root ganglion cells in a whole cell patch clamp configuration. This inhibition of I(A) likely plays a critical role in MC's ability to restore conduction in mechanically injured spinal cord axons and may present a viable alternative to 4-AP for individuals with spinal cord injury or MS. From this, compounds with greater efficacy and perhaps less side effects will likely emerge in the near future, which will greatly enhance the functional restoration and lessen the suffering of SCI and MS patients.

  2. Potassium Currents of Olfactory Bulb Juxtaglomerular Cells: Characterization, Simulation, and Implications for Plateau Potential Firing

    PubMed Central

    Masurkar, Arjun V.; Chen, Wei R.

    2011-01-01

    Odor identity is encoded by the activity of olfactory bulb glomeruli, which receive primary sensory input and transfer it to projection neurons. Juxtaglomerular cells (JGCs) may influence glomerular processing via firing of long lasting plateau potentials. Though inward currents have been investigated, little is known regarding potassium current contribution to JGC plateau potentials. We pursued study of these currents, with the overarching goal of creating components for a computational model of JGC plateau potential firing. In conditions minimizing calcium-activated potassium current (IK(Ca)), we used whole cell voltage clamp and in vitro slice preparations to characterize three potassium currents in rat JGCs. The prominent component Ikt1 displayed rapid kinetics (τ10%−90% rise 0.6–2ms, τinactivation 5–10ms) and was blocked by high concentration 4-AP (5mM) and TEA (40mM). It had half maximal activation at −10mV (V½max) and little inactivation at rest. Ikt2, with slower kinetics (τ10%−90% rise 11–15ms, τinactivation 100–300ms), was blocked by low concentration 4-AP (0.5mM) and TEA (5mM). The V½max was 0mV and inactivation was also minimal at rest. Sustained current Ikt3 showed sensitivity to low concentration 4-AP and TEA, and had V½max of +10mV. Further experiments, in conditions of physiologic calcium buffering, suggested that IK(Ca) contributed to Ikt3 with minimal effect on plateau potential evolution. We transformed these characterizations into Hodgkin-Huxley models that robustly mimicked experimental data. Further simulation demonstrated that Ikt1 would be most efficiently activated by plateau potential waveforms, predicting a critical role in shaping JGC firing. These studies demonstrated that JGCs possess a unique potassium current profile, with delayed rectifier (Ikt3), atypical A-current (Ikt1), and D-current (Ikt2) in accordance with known expression patterns in OB glomeruli. Our simulations also provide an initial framework for

  3. Quantitative interactions between the A-type K+ current and inositol trisphosphate receptors regulate intraneuronal Ca2+ waves and synaptic plasticity

    PubMed Central

    Ashhad, Sufyan; Narayanan, Rishikesh

    2013-01-01

    The A-type potassium current has been implicated in the regulation of several physiological processes. Here, we explore a role for the A-type potassium current in regulating the release of calcium through inositol trisphosphate receptors (InsP3R) that reside on the endoplasmic reticulum (ER) of hippocampal pyramidal neurons. To do this, we constructed morphologically realistic, conductance-based models equipped with kinetic schemes that govern several calcium signalling modules and pathways, and constrained the distributions and properties of constitutive components by experimental measurements from these neurons. Employing these models, we establish a bell-shaped dependence of calcium release through InsP3Rs on the density of A-type potassium channels, during the propagation of an intraneuronal calcium wave initiated through established protocols. Exploring the sensitivities of calcium wave initiation and propagation to several underlying parameters, we found that ER calcium release critically depends on dendritic diameter and that wave initiation occurred at branch points as a consequence of a high surface area to volume ratio of oblique dendrites. Furthermore, analogous to the role of A-type potassium channels in regulating spike latency, we found that an increase in the density of A-type potassium channels led to increases in the latency and the temporal spread of a propagating calcium wave. Next, we incorporated kinetic models for the metabotropic glutamate receptor (mGluR) signalling components and a calcium-controlled plasticity rule into our model and demonstrate that the presence of mGluRs induced a leftward shift in a Bienenstock–Cooper–Munro-like synaptic plasticity profile. Finally, we show that the A-type potassium current could regulate the relative contribution of ER calcium to synaptic plasticity induced either through 900 pulses of various stimulus frequencies or through theta burst stimulation. Our results establish a novel form of interaction

  4. Chlorthalidone inhibits the KvLQT1 potassium current in guinea-pig ventricular myocytes and oocytes from Xenopus laevis

    PubMed Central

    Mancilla-Simbro, C; López, A; Martinez-Morales, E; Soto-Perez-de-Celis, E; Millan-PerezPeña, L; Tsushima, R; Salinas-Stefanon, E M

    2007-01-01

    Background and purpose: Chlorthalidone is used for the treatment of hypertension as it produces a lengthening of the cardiac action potential. However, there is no experimental evidence that chlorthalidone has electrophysiological effects on the potassium currents involved in cardiac repolarization. Experimental approach: Ventricular myocytes and oocytes, transfected with human ionic channels that produce IK current, were exposed to different concentrations of chlorthalidone. Action potentials and potassium currents were recorded using a patch clamp technique. To determine which component of the current was affected by chlorthalidone, human channel proteins (hERG, minK and KvLQT1) were used. Key results: Chlorthalidone prolonged the ventricular action potential at 50 and 90% by 13 and 14%, respectively. The cardiac potassium currents I to and IK1 were not affected by chlorthalidone at any concentration, whereas the delayed rectifier potassium current, IK, was blocked in a dose-response, voltage-independent fashion. In our preparation, 100 μM chlorthalidone blocked the two components of the delayed rectifier potassium current with the same potency (50.1±5% for IKr and 54.6±6% for IKs) (n=7, P<0.05). The chlorthalidone-sensitive current was slow and saturated at potentials greater than +30 mV. In our conditions only the KvLQT1 potassium current was affected by the drug, by 14%. Conclusions and implications: Chlorthalidone was demonstrated to have a direct effect on cardiac ventricular myocytes; it blocked the delayed rectifier potassium current (IK), specifically the KvLQT1 component of the potassium current. These results indicate that it has potential for use as an antiarrhythmic but further studies are needed. PMID:18037918

  5. A point mutation of the alpha 2-adrenoceptor that blocks coupling to potassium but not calcium currents.

    PubMed

    Surprenant, A; Horstman, D A; Akbarali, H; Limbird, L E

    1992-08-14

    The alpha 2A-adrenergic receptor (adrenoceptor) was stably expressed in AtT20 mouse pituitary tumor cells; adrenoceptor agonists inhibited adenylyl cyclase, inhibited voltage-dependent calcium currents, and increased inwardly rectifying potassium currents. An aspartic acid residue (Asp79) highly conserved among guanine nucleotide-binding protein (G protein)-coupled receptors was mutated to asparagine; in cells transfected with the mutant alpha 2-receptor, agonists inhibited adenylyl cyclase and calcium currents but did not increase potassium currents. Because distinct G proteins appear to couple adrenoceptors to potassium and calcium currents, the present findings suggest that the mutant alpha 2-adrenoceptor cannot achieve the conformation necessary to activate G proteins that mediate potassium channel activation.

  6. Block of Kv1.7 potassium currents increases glucose-stimulated insulin secretion.

    PubMed

    Finol-Urdaneta, Rocio K; Remedi, Maria S; Raasch, Walter; Becker, Stefan; Clark, Robert B; Strüver, Nina; Pavlov, Evgeny; Nichols, Colin G; French, Robert J; Terlau, Heinrich

    2012-05-01

    Glucose-stimulated insulin secretion (GSIS) relies on repetitive, electrical spiking activity of the beta cell membrane. Cyclic activation of voltage-gated potassium channels (K(v) ) generates an outward, 'delayed rectifier' potassium current, which drives the repolarizing phase of each spike and modulates insulin release. Although several K(v) channels are expressed in pancreatic islets, their individual contributions to GSIS remain incompletely understood. We take advantage of a naturally occurring cone-snail peptide toxin, Conkunitzin-S1 (Conk-S1), which selectively blocks K(v) 1.7 channels to provide an intrinsically limited, finely graded control of total beta cell delayed rectifier current and hence of GSIS. Conk-S1 increases GSIS in isolated rat islets, likely by reducing K(v) 1.7-mediated delayed rectifier currents in beta cells, which yields increases in action potential firing and cytoplasmic free calcium. In rats, Conk-S1 increases glucose-dependent insulin secretion without decreasing basal glucose. Thus, we conclude that K(v) 1.7 contributes to the membrane-repolarizing current of beta cells during GSIS and that block of this specific component of beta cell K(v) current offers a potential strategy for enhancing GSIS with minimal risk of hypoglycaemia during metabolic disorders such as Type 2 diabetes.

  7. Adenosine modulation of potassium currents in postganglionic neurones of cultured avian ciliary ganglia.

    PubMed Central

    Bennett, M. R.; Kerr, R.; Nichol, K.

    1991-01-01

    1. Potassium currents in cultured postganglionic neurones of avian ciliary ganglia were analysed under whole-cell voltage clamp and their modulation by adenosine determined. 2. In the presence of tetrodotoxin (200 nM), and with moderate holding potentials (Vh = -40 mV), the steady-state current-voltage (I/V) curve was N-shaped over the range from -70 mV to +155 mV. CsCl (1 M) blocked the current, indicating that it was carried by K+. If Ca2+ influx was blocked by CdCl2 (500 microM) then the outward current was reduced and the N-shaped I-V curve lost, indicating the presence of a calcium-activated potassium current (IK(Ca)); the remaining current, due to the delayed rectifier (IK), increased with depolarization up to about a conductance of 10 nS near + 50 mV. This IK was 50% activated at about +20 mV and 50% inactivated at about -50 mV. Adenosine (10 microM) had similar affects on the N-shaped I/V curve as did CdCl2, indicating that it blocked IK(Ca). However, adenosine had little affect on the steady-state current in the presence of CdCl, indicating that it did not much affect IK. 3. In the presence of tetrodotoxin (200 nM), a large inward current occurred for large hyperpolarizations from a Vh = -50 mV. This inward rectifying current (IIR) had a reversal potential near EK and showed 50% activation at about -130 mV. Adenosine (10 microM) reduced IIR, by as much as 50% at large hyperpolarizations beyond -80 mV.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1797312

  8. Evaluation of eddy-current proximity devices for measuring thin potassium film thicknesses

    NASA Technical Reports Server (NTRS)

    Asadourian, A. S.

    1972-01-01

    Two eddy current proximity probe systems were tested over a range of 0 to 508 micrometers (0 to 20 mils) of simulated potassium film thicknesses for simulated temperatures of 66 C (150 F), 232 C (450 F), and 666 C (1230 F). The results of short time calibration tests are presented. Instrument drift was a problem throughout the testing and, without correction, may limit the use of such systems to short periods of time. Additional development will be required prior to their being usable as practical instrumentation systems.

  9. An increased TREK-1-like potassium current in ventricular myocytes during rat cardiac hypertrophy.

    PubMed

    Wang, Weiping; Zhang, Man; Li, Pingping; Yuan, Hui; Feng, Nan; Peng, Ying; Wang, Ling; Wang, Xiaoliang

    2013-04-01

    To elucidate the expression and identify the functional changes of 2 pore domain potassium channel TREK-1 during cardiac hypertrophy in rats, left ventricular hypertrophy was induced by subcutaneous injection with isoproterenol. Western blot was used to detect the expression of TREK-1 channel protein, and inside-out and whole-cell recordings were used to record TREK-1 currents. The results showed that TREK-1 protein expression in endocardium was slightly higher than that in epicardium in control left ventricles. However, it was obviously upregulated by 89.8% during hypertrophy, 2.3-fold higher than in epicardium. Mechanical stretch, intracellular acidification, and arachidonic acid could activate a TREK-1-like current in cardiomyocytes. The slope conductances of cardiac TREK-1 and CHO/TREK-1 channels were 123 ± 7 and 113 ± 17 pS, respectively. The TREK-1 inhibitor L-3-n-butylphthalide (10 μM) reduced the currents in CHO/TREK-1 cells, normal cardiomyocytes, and hypertrophic cardiomyocytes by 48.5%, 54.3%, and 55.5%, respectively. The percentage of L-3-n-butylphthalide-inhibited outward whole-cell current in hypertrophic cardiomyocytes (23.7%) was larger than that in normal cardiomyocytes (14.2%). The percentage of chloroform-activated outward whole-cell current in hypertrophic cardiomyocytes (58.3%) was also larger than normal control (40.2%). Our results demonstrated that in hypertrophic rats, TREK-1 protein expression in endocardium was specifically increased and the ratio of TREK-1 channel current in cardiac outward currents was also enhanced. TREK-1 might balance potassium ion flow during hypertrophy and might be a potential drug target for heart protection.

  10. A Small Potassium Current in AgRP/NPY Neurons Regulates Feeding Behavior and Energy Metabolism.

    PubMed

    He, Yanlin; Shu, Gang; Yang, Yongjie; Xu, Pingwen; Xia, Yan; Wang, Chunmei; Saito, Kenji; Hinton, Antentor; Yan, Xiaofeng; Liu, Chen; Wu, Qi; Tong, Qingchun; Xu, Yong

    2016-11-08

    Neurons that co-express agouti-related peptide (AgRP) and neuropeptide Y (NPY) are indispensable for normal feeding behavior. Firing activities of AgRP/NPY neurons are dynamically regulated by energy status and coordinate appropriate feeding behavior to meet nutritional demands. However, intrinsic mechanisms that regulate AgRP/NPY neural activities during the fed-to-fasted transition are not fully understood. We found that AgRP/NPY neurons in satiated mice express high levels of the small-conductance calcium-activated potassium channel 3 (SK3) and are inhibited by SK3-mediated potassium currents; on the other hand, food deprivation suppresses SK3 expression in AgRP/NPY neurons, and the decreased SK3-mediated currents contribute to fasting-induced activation of these neurons. Genetic mutation of SK3 specifically in AgRP/NPY neurons leads to increased sensitivity to diet-induced obesity, associated with chronic hyperphagia and decreased energy expenditure. Our results identify SK3 as a key intrinsic mediator that coordinates nutritional status with AgRP/NPY neural activities and animals' feeding behavior and energy metabolism.

  11. A naturally occurring omega current in a Kv3 family potassium channel from a platyhelminth.

    PubMed

    Klassen, Tara L; Spencer, Andrew N; Gallin, Warren J

    2008-06-19

    Voltage-gated ion channels are membrane proteins containing a selective pore that allows permeable ions to transit the membrane in response to a change in the transmembrane voltage. The typical selectivity filter in potassium channels is formed by a tetrameric arrangement of the carbonyl groups of the conserved amino-acid sequence Gly-Tyr-Gly. This canonical pore is opened or closed by conformational changes that originate in the voltage sensor (S4), a transmembrane helix with a series of positively charged amino acids. This sensor moves through a gating pore formed by elements of the S1, S2 and S3 helices, across the plane of the membrane, without allowing ions to pass through the membrane at that site. Recently, synthetic mutagenesis studies in the Drosophila melanogaster Shaker channel and analysis of human disease-causing mutations in sodium channels have identified amino acid residues that are integral parts of the gating-pore; when these residues are mutated the proteins allow a non-specific cation current, known as the omega current, to pass through the gating-pore with relatively low selectivity. The N.at-Kv3.2 potassium channel has an unusual weak inward rectifier phenotype. Several mutations of two amino acids in the voltage sensing (S4) transmembrane helix change the phenotype to a typical delayed rectifier. The inward rectifier channels (wild-type and mutant) are sensitive to 4-aminopyridine (4-AP) but not tetra-ethyl ammonium (TEA), whereas the delayed rectifier mutants are sensitive to TEA but not 4-AP. The inward rectifier channels also manifest low cation selectivity. The relative selectivity for different cations is sensitive to specific mutations in the S4 helix, N.at-Kv3.2, a naturally occurring potassium channel of the Kv3 sequence family, mediates ion permeation through a modified gating pore, not the canonical, highly selective pore typical of potassium channels. This channel has evolved to yield qualitatively different ion permeability when

  12. Effects of thymol on calcium and potassium currents in canine and human ventricular cardiomyocytes.

    PubMed

    Magyar, János; Szentandrássy, Norbert; Bányász, Tamás; Fülöp, László; Varró, András; Nánási, Péter P

    2002-05-01

    1. Concentration-dependent effects of thymol (1 - 1000 microM) was studied on action potential configuration and ionic currents in isolated canine ventricular cardiomyocytes using conventional microelectrode and patch clamp techniques. 2. Low concentration of thymol (10 microM) removed the notch of the action potential, whereas high concentrations (100 microM or higher) caused an additional shortening of action potential duration accompanied by progressive depression of plateau and reduction of V(max). 3. In the canine cells L-type Ca current (I(Ca)) was decreased by thymol in a concentration-dependent manner (EC(50): 158+/-7 microM, Hill coeff.: 2.96+/-0.43). In addition, thymol (50 - 250 microM) accelerated the inactivation of I(Ca), increased the time constant of recovery from inactivation, shifted the steady-state inactivation curve of I(Ca) leftwards, but voltage dependence of activation remained unaltered. Qualitatively similar results were obtained with thymol in ventricular myocytes isolated from healthy human hearts. 4. Thymol displayed concentration-dependent suppressive effects on potassium currents: the transient outward current, I(to) (EC(50): 60.6+/-11.4 microM, Hill coeff.: 1.03+/-0.11), the rapid component of the delayed rectifier, I(Kr) (EC(50): 63.4+/-6.1 microM, Hill coeff.: 1.29+/-0.15), and the slow component of the delayed rectifier, I(Ks) (EC(50): 202+/-11 microM, Hill coeff.: 0.72+/-0.14), however, K channel kinetics were not much altered by thymol. These effects on Ca and K currents developed rapidly (within 0.5 min) and were readily reversible. 5. In conclusion, thymol suppressed cardiac ionic channels in a concentration-dependent manner, however, both drug-sensitivities as well as the mechanism of action seems to be different when blocking calcium and potassium channels.

  13. Variations in the ensemble of potassium currents underlying resonance in turtle hair cells.

    PubMed Central

    Goodman, M B; Art, J J

    1996-01-01

    1. Potassium currents were characterized in turtle cochlear hair cells by whole-cell voltage clamp during superfusion with the potassium channel antagonists, tetraethylammonium (TEA) and 4-aminopyridine (4-AP). The estimated resonant frequency, f0, was inferred from tau, the time constant of deactivation of outward current upon repolarization to -50 mV, according to the empirical relation, f0 = k1 tau-1/2 + k2. 2. Dose-response relations for TEA and 4-AP were obtained by exposing single cells to ten concentrations exponentially distributed over four orders of magnitude. Potassium current in cells tuned to low frequencies was carried by a single class of channels with an apparent affinity constant, K1, for TEA of 35.9 mM. Half-blocking concentrations of 4-AP were correlated with the time constant of deactivation and varied between 26.2 and 102 microM. In cells tuned to higher frequencies, K+ current was carried by a single class of channels with high affinity for TEA (K1 = 0.215 mM) and low affinity for 4-AP (K1 = 12.3 mM). This pharmacological profile suggests that K+ current in low frequency cells is purely voltage gated and in high frequency cells, it is gated by both Ca2+ and voltage. 3. For each current type, the voltage dependence of activation was determined from tail current amplitude at -50 mV. The purely voltage-gated current, IK(V), was found to increase e-fold in 4.0 +/- 0.3 mV (n = 3) in low frequency cells exposed to TEA (25 mM). The Ca(2+)- and voltage-gated current, IK(Ca), was more steeply voltage dependent, increasing e-fold in 1.9 mV (n = 2) in high frequency cells exposed to 4-AP (0.8 mM). 4. IK(V) was found to inactivate slowly during prolonged voltage steps (approximately 10 s). Steady-state inactivation increased with depolarization from -70 mV and was incomplete such that on average IK(v) did not fall below approximately 0.39 of its maximum value. 5. Superfusion of 4-AP (0.8 mM) reversibly depolarized a low frequency cell and eliminated

  14. 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.

  15. The evolution-informed optimal dietary potassium intake of human beings greatly exceeds current and recommended intakes.

    PubMed

    Sebastian, Anthony; Frassetto, Lynda A; Sellmeyer, Deborah E; Morris, R Curtis

    2006-11-01

    An organism best fits the environment described by its genes, an environment that prevailed during the time period (millions of years) when evolution naturally selected the genes of its ancestors-those who survived to pass on their genes. When an organism's current environment differs from its ancestral one, the environment's mismatch with the organism's genome may result in functional disadvantages for the organism. The genetically conditioned nutritional requirements of human beings established themselves over millions of years in which ancestral hominins, living as hunter-gatherers, ate a diet markedly different from that of agriculturally dependent contemporary human beings. In that context, we sought to quantify the ancestral-contemporary dietary difference with respect to the supply of one of the body's major mineral nutrients: potassium. In 159 retrojected Stone Age diets, human potassium intake averaged 400 +/- 125 mEq/d, which exceeds current and recommended intakes by more than a factor of 4. We accounted for the transition to the relatively potassium-poor modern diet by the fact that the modern diet has substantially replaced Stone Age amounts of potassium-rich plant foods (especially fruits, leafy greens, vegetable fruits, roots, and tubers), with energy-dense nutrient-poor foods (separated fats, oils, refined sugars, and refined grains), and with potassium-poor energy-rich plant foods (especially cereal grains) introduced by agriculture (circa 10,000 years ago). Given the fundamental physiologic importance of potassium, such a large magnitude of change in potassium intake invites the consideration in human beings of whether the quantitative values of potassium-influenced physiologic phenomena (eg, blood pressure, insulin and aldosterone secretion rates, and intracellular pH) currently viewed as normal, in fact disaccord with genetically conditioned norms. We discuss the potential implications of our findings in respect to human health and disease.

  16. 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

  17. Large-conductance calcium-activated potassium current modulates excitability in isolated canine intracardiac neurons

    PubMed Central

    Pérez, Guillermo J.; Desai, Mayurika; Anderson, Seth

    2013-01-01

    We studied principal neurons from canine intracardiac (IC) ganglia to determine whether large-conductance calcium-activated potassium (BK) channels play a role in their excitability. We performed whole cell recordings in voltage- and current-clamp modes to measure ion currents and changes in membrane potential from isolated canine IC neurons. Whole cell currents from these neurons showed fast- and slow-activated outward components. Both current components decreased in the absence of calcium and following 1–2 mM tetraethylammonium (TEA) or paxilline. These results suggest that BK channels underlie these current components. Single-channel analysis showed that BK channels from IC neurons do not inactivate in a time-dependent manner, suggesting that the dynamic of the decay of the fast current component is akin to that of intracellular calcium. Immunohistochemical studies showed that BK channels and type 2 ryanodine receptors are coexpressed in IC principal neurons. We tested whether BK current activation in these neurons occurred via a calcium-induced calcium release mechanism. We found that the outward currents of these neurons were not affected by the calcium depletion of intracellular stores with 10 mM caffeine and 10 μM cyclopiazonic acid. Thus, in canine intracardiac neurons, BK currents are directly activated by calcium influx. Membrane potential changes elicited by long (400 ms) current injections showed a tonic firing response that was decreased by TEA or paxilline. These data strongly suggest that the BK current present in canine intracardiac neurons regulates action potential activity and could increase these neurons excitability. PMID:23195072

  18. Two types of 4-aminopyridine-sensitive potassium current in rabbit Schwann cells.

    PubMed

    Baker, M; Howe, J R; Ritchie, J M

    1993-05-01

    -AP block of delayed rectifier K+ currents. 7. In addition to types I and II, a third type of outward K+ current (type III) was generated in most cells at positive membrane potentials. This latter current was insensitive to millimolar concentrations of 4-AP. 8. Similarities between Schwann cell and neuronal potassium channels are discussed.

  19. Redox modulation of A-type K+ currents in pain-sensing dorsal root ganglion neurons.

    PubMed

    Hsieh, Chi-Pan

    2008-06-06

    Redox modulation of fast inactivation has been described in certain cloned A-type voltage-gated K(+) (Kv) channels in expressing systems, but the effects remain to be demonstrated in native neurons. In this study, we examined the effects of cysteine-specific redox agents on the A-type K(+) currents in acutely dissociated small diameter dorsal root ganglion (DRG) neurons from rats. The fast inactivation of most A-type currents was markedly removed or slowed by the oxidizing agents 2,2'-dithio-bis(5-nitropyridine) (DTBNP) and chloramine-T. Dithiothreitol, a reducing agent for the disulfide bond, restored the inactivation. These results demonstrated that native A-type K(+) channels, probably Kv1.4, could switch the roles between inactivating and non-inactivating K(+) channels via redox regulation in pain-sensing DRG neurons. The A-type channels may play a role in adjusting pain sensitivity in response to peripheral redox conditions.

  20. Moderate Hypoxia Influences Potassium Outward Currents in Adipose-Derived Stem Cells

    PubMed Central

    Prasad, Mayuri; Zachar, Vladimir; Fink, Trine; Pennisi, Cristian Pablo

    2014-01-01

    Moderate hypoxic preconditioning of adipose-derived stem cells (ASCs) enhances properties such as proliferation and secretion of growth factors, representing a valuable strategy to increase the efficiency of cell-based therapies. In a wide variety of cells potassium (K+) channels are key elements involved in the cellular responses to hypoxia, suggesting that ASCs cultured under low oxygen conditions may display altered electrophysiological properties. Here, the effects of moderate hypoxic culture on proliferation, whole-cell currents, and ion channel expression were investigated using human ASCs cultured at 5% and 20% oxygen. Although cell proliferation was greatly enhanced, the dose-dependent growth inhibition by the K+ channel blocker tetraethylammonium (TEA) was not significantly affected by hypoxia. Under both normoxic and hypoxic conditions, ASCs displayed outward K+ currents composed by Ca2+-activated, delayed rectifier, and transient components. Hypoxic culture reduced the slope of the current-voltage curves and caused a negative shift in the voltage activation threshold of the whole-cell currents. However, the TEA-mediated shift of voltage activation threshold was not affected by hypoxia. Semiquantitative real-time RT-PCR revealed that expression of genes encoding for various ion channels subunits related to oxygen sensing and proliferation remained unchanged after hypoxic culture. In conclusion, outward currents are influenced by moderate hypoxia in ASCs through a mechanism that is not likely the result of modulation of TEA-sensitive K+ channels. PMID:25115627

  1. Osteoclast spreading kinetics are correlated with an oscillatory activation of a calcium-dependent potassium current.

    PubMed

    Espinosa, Leon; Paret, Laurent; Ojeda, Carlos; Tourneur, Yves; Delmas, Pierre D; Chenu, Chantal

    2002-10-01

    Cell movement and spreading involve calcium-dependent processes and ionic channel activation. During bone resorption, osteoclasts alternate between spread, motile and resorptive phases. We investigated whether the electrical membrane properties of osteoclasts were linked to their membrane morphological changes. Rabbit osteoclasts were recorded by time-lapse videomicroscopy performed simultaneously with patch-clamp whole cell and single channel recordings. Original image analysis methods were developed and used to demonstrate for the first time an oscillatory activation of a spontaneous membrane current in osteoclasts, which is directly correlated to the membrane movement rate. This current was identified as a calcium-dependent potassium current (IK(Ca)) that is sensitive to both charybdotoxin and apamin and was generated by a channel with unitary conductance of approximately 25+/-2 pS. Blockade of this current also decreased osteoclast spreading and inhibited bone resorption in vitro, demonstrating a physiological role for this current in osteoclast activity. These results establish for the first time a temporal correlation between lamellipodia formation kinetics and spontaneous peaks of IK(Ca), which are both involved in the control of osteoclast spreading and bone resorption.

  2. Regulation by second messengers of the slowly activating, voltage-dependent potassium current expressed in Xenopus oocytes.

    PubMed Central

    Busch, A E; Kavanaugh, M P; Varnum, M D; Adelman, J P; North, R A

    1992-01-01

    1. Voltage-clamp recordings of membrane current were made from Xenopus oocytes that had been injected with RNA which had been transcribed in vitro from a cloned complementary DNA. 2. Depolarization from -80 mV evoked outward potassium currents that developed very slowly. At -20 mV the time constant for activation was about 50 s, and at +40 mV about 6 s. 3. The potassium current was increased by the calcium ionophore A23187 or by intracellular injection of inositol 1,4,5-trisphosphate (IP3), each of which should increase the intracellular calcium concentration ([Ca2+]i). The current was decreased by injection of BAPTA (1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid). The current was also reduced by phorbol esters; this effect was blocked by staurosporine. 4. In oocytes that had also been injected with RNA encoding the 5-hydroxytryptamine (5-HT2) receptor, 5-HT increased the potassium current. After caffeine pretreatment, to block the release of intracellular calcium, 5-HT decreased the current; this decrease was prevented by staurosporine. 5. It is concluded that the slowly activating, voltage-dependent potassium current expressed in Xenopus oocytes is increased by increases in [Ca2+]i and is decreased by activation of protein kinase C. Stimulation of 5-HT2 receptors can have both these effects, but the former normally predominates. Images Fig. 4 PMID:1432714

  3. Decreased inward rectifier potassium current IK1 in dystrophin-deficient ventricular cardiomyocytes

    PubMed Central

    Rubi, Lena; Koenig, Xaver; Kubista, Helmut; Todt, Hannes; Hilber, Karlheinz

    2017-01-01

    ABSTRACT Kir2.x channels in ventricular cardiomyocytes (most prominently Kir2.1) account for the inward rectifier potassium current IK1, which controls the resting membrane potential and the final phase of action potential repolarization. Recently it was hypothesized that the dystrophin-associated protein complex (DAPC) is important in the regulation of Kir2.x channels. To test this hypothesis, we investigated potential IK1 abnormalities in dystrophin-deficient ventricular cardiomyocytes derived from the hearts of Duchenne muscular dystrophy mouse models. We found that IK1 was substantially diminished in dystrophin-deficient cardiomyocytes when compared to wild type myocytes. This finding represents the first functional evidence for a significant role of the DAPC in the regulation of Kir2.x channels. PMID:27560040

  4. Decreased inward rectifier potassium current IK1 in dystrophin-deficient ventricular cardiomyocytes.

    PubMed

    Rubi, Lena; Koenig, Xaver; Kubista, Helmut; Todt, Hannes; Hilber, Karlheinz

    2017-03-04

    Kir2.x channels in ventricular cardiomyocytes (most prominently Kir2.1) account for the inward rectifier potassium current IK1, which controls the resting membrane potential and the final phase of action potential repolarization. Recently it was hypothesized that the dystrophin-associated protein complex (DAPC) is important in the regulation of Kir2.x channels. To test this hypothesis, we investigated potential IK1 abnormalities in dystrophin-deficient ventricular cardiomyocytes derived from the hearts of Duchenne muscular dystrophy mouse models. We found that IK1 was substantially diminished in dystrophin-deficient cardiomyocytes when compared to wild type myocytes. This finding represents the first functional evidence for a significant role of the DAPC in the regulation of Kir2.x channels.

  5. Effects of potassium channel openers on Na+ and K+ currents in rabbit sinus node and atrial myocytes.

    PubMed

    Tromba, C; Cohen, I S

    1995-05-12

    The effects of the potassium channel openers (KCOs) Cromakalim and Lemakalim on rabbit sinoatrial and atrial myocytes were examined by means of the whole-cell patch-clamp technique. Lemakalin (up to 100 microM) had no effect on potassium current in sinoatrial cells. Both Lemakalim and Cromakalim (100 microM) displayed a two-fold action on atrial myocytes: (1) they increased an outwardly rectifying conductance at potentials positive to EK and, (2) they markedly decreased a TTX-sensitive Na+ current active in the voltage range -50/-30 mV. This novel action on TTX-sensitive currents is of particular interest since these two benzopyrans have been thought to specifically target potassium channels.

  6. Tubocurarine blocks a calcium-dependent potassium current in rat tumoral pituitary cells.

    PubMed

    Vacher, P; Vacher, A M; Mollard, P

    1998-04-30

    We investigated the effects of potassium channel inhibitors on electrical activity, membrane ionic currents, intracellular calcium concentration ([Ca2+]i) and hormone release in GH3/B6 cells (a line of pituitary origin). Patch-clamp recordings show a two-component after hyperpolarization (AHP) following each action potential (current clamp) or a two-component tail current (voltage-clamp). Both components can be blocked by inhibiting Ca2+ influx. Application of D-tubocurarine (dTc) (20-500 microM) reversibly suppressed the slowly decaying Ca2+-activated K+ tail current (I AHPs) in a concentration-dependent manner. On the other hand, low doses of tetraethylammonium ions (TEA+) only blocked the rapidly decaying voltage- and Ca2+-activated K+ tail current (I AHPf). Therefore, GH3/B6 cells exhibit at least two quite distinct Ca2+-dependent K+ currents, which differ in size, voltage- and Ca2+-sensitivity, kinetics and pharmacology. These two currents also play quite separate roles in shaping the action potential. d-tubocurarine increased spontaneous Ca2+ action potential firing, whereas TEA increased action potential duration. Thus, both agents stimulated Ca2+ entry. I AHPs is activated by a transient increase in [Ca2+]i such as a thyrotrophin releasing hormone-induced Ca2+ mobilization. All the K+ channel inhibitors we tested: TEA, apamin, dTC and charybdotoxin, stimulated prolactin and growth hormone release in GH3/B6 cells. Our results show that I AHPs is a good sensor for subplasmalemmal Ca2+ and that dTc is a good pharmacological tool for studying this current.

  7. Effects of allitridum on the transient outward potassium current in rats with heart failure

    PubMed Central

    Zhao, Xiao-Jing; Lin, Kun; Zhang, Yu; Xu, Bin; Liu, Li; Fu, Yi-Cheng; Chen, Xi; Cai, Zhong-Qi; Wu, Zhi-Juan; Huang, Yun; Li, Yang

    2016-01-01

    Objective To study the effect of allitridum on the transient outward potassium current (Ito) of ventricular myocytes in heart failure (HF). Methods The dual enzymatic method was used to separate single ventricular myocytes from Sprague Dawley rats. Patch-clamping was used to record Ito and analyze the effect of allitridum on the current. Results The Ito current had a significant decrease in the HF group, compared with the control group. The density of Ito in the HF group was increased after treatment of allitridum (30 µmol/L). The peak current densities of Ito were enhanced in the HF group from 6.01 ± 0.30 pA/pF to 8.41 ± 0.54 pA/pF (P < 0.01) at +50 mV after treatment with allitridum (30 µmol/L). We also determined the effect of allitridum on the gating mechanism of the Ito in the HF group. Conclusions We found that allitridum increased the Ito by accelerating the activation of channels and shortened the time constants of inactivation, and allitridum decreased the remodeling of Ito in ventricular myocytes of rats with HF. PMID:27899943

  8. Gastrin Releasing Peptide Modulates Fast Delayed Rectifier Potassium Current in Per1-Expressing SCN Neurons

    PubMed Central

    Gamble, Karen L.; Kudo, Takashi; Colwell, Christopher S.; McMahon, Douglas G.

    2011-01-01

    The mammalian circadian clock in the suprachiasmatic nucleus (SCN) drives and maintains 24-h physiological rhythms, the phases of which are set by the local environmental light-dark cycle. Gastrin releasing peptide (GRP) communicates photic phase setting signals in the SCN by increasing neurophysiological activity of SCN neurons. Here, the ionic basis for persistent GRP-induced changes in neuronal activity was investigated in SCN slice cultures from Per1::GFP reporter mice during the early night. Recordings from Per1-fluorescent neurons in SCN slices several hours after GRP treatment revealed a significantly greater action potential frequency, a significant increase in voltage-activated outward current at depolarized potentials, and a significant increase in 4-aminopyridine (4-AP) sensitive fast delayed rectifier (fDR) potassium currents when compared to vehicle-treated slices. In addition, the persistent increase in spike rate following early night GRP application was blocked in SCN neurons from mice deficient in Kv3 channel proteins. Because fDR currents are regulated by the clock and are elevated in amplitude during the day, the present results support the model that GRP delays the phase of the clock during the early night by prolonging day-like membrane properties of SCN cells. Furthermore, these findings implicate fDR currents in the ionic basis for GRP-mediated entrainment of the primary mammalian circadian pacemaker. PMID:21454290

  9. Analysis of the effects of calcium or magnesium on voltage-clamp currents in perfused squid axons bathed in solutions of high potassium.

    PubMed

    Rojas, E; Taylor, R E; Atwater, I; Bezanilla, F

    1969-10-01

    Isolated axons from the squid, Dosidicus gigas, were internally perfused with potassium fluoride solutions. Membrane currents were measured following step changes of membrane potential in a voltage-clamp arrangement with external isosmotic solution changes in the order: potassium-free artificial seawater; potassium chloride; potassium chloride containing 10, 25, 40 or 50, mM calcium or magnesium; and potassium-free artificial seawater. The following results suggest that the currents measured under voltage clamp with potassium outside and inside can be separated into two components and that one of them, the predominant one, is carried through the potassium system. (a) Outward currents in isosmotic potassium were strongly and reversibly reduced by tetraethylammonium chloride. (b) Without calcium or magnesium a progressive increase in the nontime-dependent component of the currents (leakage) occurred. (c) The restoration of calcium or magnesium within 15-30 min decreases this leakage. (d) With 50 mM divalent ions the steady-state current-voltage curve was nonlinear with negative resistance as observed in intact axons in isosmotic potassium. (e) The time-dependent components of the membrane currents were not clearly affected by calcium or magnesium. These results show a strong dependence of the leakage currents on external calcium or magnesium concentration but provide no support for the involvement of calcium or magnesium in the kinetics of the potassium system.

  10. Analysis of the Effects of Calcium or Magnesium on Voltage-Clamp Currents in Perfused Squid Axons Bathed in Solutions of High Potassium

    PubMed Central

    Rojas, Eduardo; Taylor, Robert E.; Atwater, Illani; Bezanilla, Francisco

    1969-01-01

    Isolated axons from the squid, Dosidicus gigas, were internally perfused with potassium fluoride solutions. Membrane currents were measured following step changes of membrane potential in a voltage-clamp arrangement with external isosmotic solution changes in the order: potassium-free artificial seawater; potassium chloride; potassium chloride containing 10, 25, 40 or 50, mM calcium or magnesium; and potassium-free artificial seawater. The following results suggest that the currents measured under voltage clamp with potassium outside and inside can be separated into two components and that one of them, the predominant one, is carried through the potassium system. (a) Outward currents in isosmotic potassium were strongly and reversibly reduced by tetraethylammonium chloride. (b) Without calcium or magnesium a progressive increase in the nontime-dependent component of the currents (leakage) occurred. (c) The restoration of calcium or magnesium within 15–30 min decreases this leakage. (d) With 50 mM divalent ions the steady-state current-voltage curve was nonlinear with negative resistance as observed in intact axons in isosmotic potassium. (e) The time-dependent components of the membrane currents were not clearly affected by calcium or magnesium. These results show a strong dependence of the leakage currents on external calcium or magnesium concentration but provide no support for the involvement of calcium or magnesium in the kinetics of the potassium system. PMID:5823216

  11. Effects of thymol on calcium and potassium currents in canine and human ventricular cardiomyocytes

    PubMed Central

    Magyar, János; Szentandrássy, Norbert; Bányász, Tamás; Fülöp, László; Varró, András; Nánási, Péter P

    2002-01-01

    Concentration-dependent effects of thymol (1–1000 μM) was studied on action potential configuration and ionic currents in isolated canine ventricular cardiomyocytes using conventional microelectrode and patch clamp techniques.Low concentration of thymol (10 μM) removed the notch of the action potential, whereas high concentrations (100 μM or higher) caused an additional shortening of action potential duration accompanied by progressive depression of plateau and reduction of Vmax.In the canine cells L-type Ca current (ICa) was decreased by thymol in a concentration-dependent manner (EC50: 158±7 μM, Hill coeff.: 2.96±0.43). In addition, thymol (50–250 μM) accelerated the inactivation of ICa, increased the time constant of recovery from inactivation, shifted the steady-state inactivation curve of ICa leftwards, but voltage dependence of activation remained unaltered. Qualitatively similar results were obtained with thymol in ventricular myocytes isolated from healthy human hearts.Thymol displayed concentration-dependent suppressive effects on potassium currents: the transient outward current, Ito (EC50: 60.6±11.4 μM, Hill coeff.: 1.03±0.11), the rapid component of the delayed rectifier, IKr (EC50: 63.4±6.1 μM, Hill coeff.: 1.29±0.15), and the slow component of the delayed rectifier, IKs (EC50: 202±11 μM, Hill coeff.: 0.72±0.14), however, K channel kinetics were not much altered by thymol. These effects on Ca and K currents developed rapidly (within 0.5 min) and were readily reversible.In conclusion, thymol suppressed cardiac ionic channels in a concentration-dependent manner, however, both drug-sensitivities as well as the mechanism of action seems to be different when blocking calcium and potassium channels. PMID:12010783

  12. Inward rectifier potassium (Kir) current in dopaminergic periglomerular neurons of the mouse olfactory bulb.

    PubMed

    Borin, Mirta; Fogli Iseppe, Alex; Pignatelli, Angela; Belluzzi, Ottorino

    2014-01-01

    Dopaminergic (DA) periglomerular (PG) neurons are critically placed at the entry of the bulbar circuitry, directly in contact with both the terminals of olfactory sensory neurons and the apical dendrites of projection neurons; they are autorhythmic and are the target of numerous terminals releasing a variety of neurotransmitters. Despite the centrality of their position, suggesting a critical role in the sensory processing, their properties -and consequently their function- remain elusive. The current mediated by inward rectifier potassium (Kir) channels in DA-PG cells was recorded by adopting the perforated-patch configuration in thin slices; IKir could be distinguished from the hyperpolarization-activated current (I h ) by showing full activation in <10 ms, no inactivation, suppression by Ba(2+) in a typical voltage-dependent manner (IC50 208 μM) and reversal potential nearly coincident with EK. Ba(2+) (2 mM) induces a large depolarization of DA-PG cells, paralleled by an increase of the input resistance, leading to a block of the spontaneous activity, but the Kir current is not an essential component of the pacemaker machinery. The Kir current is negatively modulated by intracellular cAMP, as shown by a decrease of its amplitude induced by forskolin or 8Br-cAMP. We have also tested the neuromodulatory effects of the activation of several metabotropic receptors known to be present on these cells, showing that the current can be modulated by a multiplicity of pathways, whose activation in some case increases the amplitude of the current, as can be observed with agonists of D2, muscarinic, and GABAA receptors, whereas in other cases has the opposite effect, as it can be observed with agonists of α1 noradrenergic, 5-HT and histamine receptors. These characteristics of the Kir currents provide the basis for an unexpected plasticity of DA-PG cell function, making them potentially capable to reconfigure the bulbar network to allow a better flexibility.

  13. Astroglial potassium clearance contributes to short-term plasticity of synaptically evoked currents at the tripartite synapse.

    PubMed

    Sibille, Jérémie; Pannasch, Ulrike; Rouach, Nathalie

    2014-01-01

    Astroglial processes enclose ∼60% of CA1 hippocampal synapses to form the tripartite synapse. Although astrocytes express ionic channels, neurotransmitter receptors and transporters to detect neuronal activity, the nature, plasticity and impact of the currents induced by neuronal activity on short-term synaptic plasticity remain elusive in hippocampal astrocytes. Using simultaneous electrophysiological recordings of astrocytes and neurons, we found that single stimulation of Schaffer collaterals in hippocampal slices evokes in stratum radiatum astrocytes a complex prolonged inward current synchronized to synaptic and spiking activity in CA1 pyramidal cells. The astroglial current is composed of three components sensitive to neuronal activity, i.e. a long-lasting potassium current mediated by Kir4.1 channels, a transient glutamate transporter current and a slow residual current, partially mediated by GABA transporters and Kir4.1-independent potassium channels. We show that all astroglial membrane currents exhibit activity-dependent short-term plasticity. However, only the astroglial glutamate transporter current displays neuronal-like dynamics and plasticity. As Kir4.1 channel-mediated potassium uptake contributes to 80% of the synaptically evoked astroglial current, we investigated in turn its impact on short-term synaptic plasticity. Using glial conditional Kir4.1 knockout mice, we found that astroglial potassium uptake reduces synaptic responses to repetitive stimulation and post-tetanic potentiation. These results show that astrocytes integrate synaptic activity via multiple ionic channels and transporters and contribute to short-term plasticity in part via potassium clearance mediated by Kir4.1 channels.

  14. Astroglial potassium clearance contributes to short-term plasticity of synaptically evoked currents at the tripartite synapse

    PubMed Central

    Sibille, Jérémie; Pannasch, Ulrike; Rouach, Nathalie

    2014-01-01

    Abstract Astroglial processes enclose ∼60% of CA1 hippocampal synapses to form the tripartite synapse. Although astrocytes express ionic channels, neurotransmitter receptors and transporters to detect neuronal activity, the nature, plasticity and impact of the currents induced by neuronal activity on short-term synaptic plasticity remain elusive in hippocampal astrocytes. Using simultaneous electrophysiological recordings of astrocytes and neurons, we found that single stimulation of Schaffer collaterals in hippocampal slices evokes in stratum radiatum astrocytes a complex prolonged inward current synchronized to synaptic and spiking activity in CA1 pyramidal cells. The astroglial current is composed of three components sensitive to neuronal activity, i.e. a long-lasting potassium current mediated by Kir4.1 channels, a transient glutamate transporter current and a slow residual current, partially mediated by GABA transporters and Kir4.1-independent potassium channels. We show that all astroglial membrane currents exhibit activity-dependent short-term plasticity. However, only the astroglial glutamate transporter current displays neuronal-like dynamics and plasticity. As Kir4.1 channel-mediated potassium uptake contributes to 80% of the synaptically evoked astroglial current, we investigated in turn its impact on short-term synaptic plasticity. Using glial conditional Kir4.1 knockout mice, we found that astroglial potassium uptake reduces synaptic responses to repetitive stimulation and post-tetanic potentiation. These results show that astrocytes integrate synaptic activity via multiple ionic channels and transporters and contribute to short-term plasticity in part via potassium clearance mediated by Kir4.1 channels. PMID:24081156

  15. Sodium-activated potassium channels are functionally coupled to persistent sodium currents.

    PubMed

    Hage, Travis A; Salkoff, Lawrence

    2012-02-22

    We report a novel coupled system of sodium-activated potassium currents (I(KNa)) and persistent sodium currents (I(NaP)), the components of which are widely distributed throughout the brain. Its existence and importance has not been previously recognized. Although I(KNa) was known to exist in many cell types, the source of Na(+) which activates I(KNa) remained a mystery. We now show in single membrane patches generated from the somas of rat neurons that sodium influx through I(NaP) is sufficient for activation of K(Na) channels, without substantial contribution from the transient sodium current or bulk [Na(+)](i). I(NaP) was found to be active at cell membrane resting potentials, a finding that may explain why I(KNa) can be evoked from negative holding potentials. These results show an unanticipated role for I(NaP) in activating a negative feedback system countering the excitable effects I(NaP); the interrelatedness of I(NaP) and I(KNa) suggests new ways neurons can tune their excitability.

  16. Nicotine at clinically relevant concentrations affects atrial inward rectifier potassium current sensitive to acetylcholine.

    PubMed

    Bébarová, Markéta; Matejovič, Peter; Švecová, Olga; Kula, Roman; Šimurdová, Milena; Šimurda, Jiří

    2017-05-01

    Nicotine abuse is associated with variety of diseases including arrhythmias, most often atrial fibrillation (AF). Altered inward rectifier potassium currents including acetylcholine-sensitive current I K(Ach) are known to be related to AF pathogenesis. Since relevant data are missing, we aimed to investigate I K(Ach) changes at clinically relevant concentrations of nicotine. Experiments were performed by the whole cell patch clamp technique at 23 ± 1 °C on isolated rat atrial myocytes. Nicotine was applied at following concentrations: 4, 40 and 400 nM; ethanol at 20 mM (∼0.09%). Nicotine at 40 and 400 nM significantly activated constitutively active component of I K(Ach) with the maximum effect at 40 nM (an increase by ∼100%); similar effect was observed at -110 and -50 mV. Changes at 4 nM nicotine were negligible on average. Coapplication of 40 nM nicotine and 20 mM ethanol (which is also known to activate this current) did not show cumulative effect. In the case of acetylcholine-induced component of I K(Ach), a dual effect of nicotine and its correlation with the current magnitude in control were apparent: the current was increased by nicotine in the cells showing small current in control and vice versa. The effect of 40 and 400 nM nicotine on acetylcholine-induced component of I K(Ach) was significantly different at -110 and -50 mV. We conclude that nicotine at clinically relevant concentrations significantly increased constitutively active component of I K(Ach) and showed a dual effect on its acetylcholine-induced component, similarly as ethanol. Synchronous application of nicotine and ethanol did not cause additive effect.

  17. Effect of ethanol at clinically relevant concentrations on atrial inward rectifier potassium current sensitive to acetylcholine.

    PubMed

    Bébarová, Markéta; Matejovič, Peter; Pásek, Michal; Hořáková, Zuzana; Hošek, Jan; Šimurdová, Milena; Šimurda, Jiří

    2016-10-01

    Alcohol intoxication tends to induce arrhythmias, most often the atrial fibrillation. To elucidate arrhythmogenic mechanisms related to alcohol consumption, the effect of ethanol on main components of the ionic membrane current is investigated step by step. Considering limited knowledge, we aimed to examine the effect of clinically relevant concentrations of ethanol (0.8-80 mM) on acetylcholine-sensitive inward rectifier potassium current I K(Ach). Experiments were performed by the whole-cell patch clamp technique at 23 ± 1 °C on isolated rat and guinea-pig atrial myocytes, and on expressed human Kir3.1/3.4 channels. Ethanol induced changes of I K(Ach) in the whole range of concentrations applied; the effect was not voltage dependent. The constitutively active component of I K(Ach) was significantly increased by ethanol with the maximum effect (an increase by ∼100 %) between 8 and 20 mM. The changes were comparable in rat and guinea-pig atrial myocytes and also in expressed human Kir3.1/3.4 channels (i.e., structural correlate of I K(Ach)). In the case of the acetylcholine-induced component of I K(Ach), a dual ethanol effect was apparent with a striking heterogeneity of changes in individual cells. The effect correlated with the current magnitude in control: the current was increased by eth-anol in the cells showing small current in control and vice versa. The average effect peaked at 20 mM ethanol (an increase of the current by ∼20 %). Observed changes of action potential duration agreed well with the voltage clamp data. Ethanol significantly affected both components of I K(Ach) even in concentrations corresponding to light alcohol consumption.

  18. Voltage-dependent potassium currents during fast spikes of rat cerebellar Purkinje neurons: inhibition by BDS-I toxin.

    PubMed

    Martina, Marco; Metz, Alexia E; Bean, Bruce P

    2007-01-01

    We characterized the kinetics and pharmacological properties of voltage-activated potassium currents in rat cerebellar Purkinje neurons using recordings from nucleated patches, which allowed high resolution of activation and deactivation kinetics. Activation was exceptionally rapid, with 10-90% activation in about 400 mus at +30 mV, near the peak of the spike. Deactivation was also extremely rapid, with a decay time constant of about 300 mus near -80 mV. These rapid activation and deactivation kinetics are consistent with mediation by Kv3-family channels but are even faster than reported for Kv3-family channels in other neurons. The peptide toxin BDS-I had very little blocking effect on potassium currents elicited by 100-ms depolarizing steps, but the potassium current evoked by action potential waveforms was inhibited nearly completely. The mechanism of inhibition by BDS-I involves slowing of activation rather than total channel block, consistent with the effects described in cloned Kv3-family channels and this explains the dramatically different effects on currents evoked by short spikes versus voltage steps. As predicted from this mechanism, the effects of toxin on spike width were relatively modest (broadening by roughly 25%). These results show that BDS-I-sensitive channels with ultrafast activation and deactivation kinetics carry virtually all of the voltage-dependent potassium current underlying repolarization during normal Purkinje cell spikes.

  19. Simulations of ion current in realistic models of ion channels: the KcsA potassium channel.

    PubMed

    Burykin, A; Schutz, C N; Villá, J; Warshel, A

    2002-05-15

    Realistic studies of ion current in biologic channels present a major challenge for computer simulation approaches. All-atom molecular dynamics simulations involve serious time limitations that prevent their use in direct evaluation of ion current in channels with significant barriers. The alternative use of Brownian dynamics (BD) simulations can provide the current for simplified macroscopic models. However, the time needed for accurate calculations of electrostatic energies can make BD simulations of ion current expensive. The present work develops an approach that overcomes some of the above challenges and allows one to simulate ion currents in models of biologic channels. Our method provides a fast and reliable estimate of the energetics of the system by combining semimacroscopic calculations of the self-energy of each ion and an implicit treatment of the interactions between the ions, as well as the interactions between the ions and the protein-ionizable groups. This treatment involves the use of the semimacroscopic version of the protein dipole Langevin dipole (PDLD/S) model in its linear response approximation (LRA) implementation, which reduces the uncertainties about the value of the protein "dielectric constant." The resulting free energy surface is used to generate the forces for on-the-fly BD simulations of the corresponding ion currents. Our model is examined in a preliminary simulation of the ion current in the KcsA potassium channel. The complete free energy profile for a single ion transport reflects reasonable energetics and captures the effect of the protein-ionized groups. This calculated profile indicates that we are dealing with the channel in its closed state. Reducing the barrier at the gate region allows us to simulate the ion current in a reasonable computational time. Several limiting cases are examined, including those that reproduce the observed current, and the nature of the productive trajectories is considered. The ability to simulate

  20. Voltage-gated potassium currents within the dorsal vagal nucleus: inhibition by BDS toxin.

    PubMed

    Dallas, Mark L; Morris, Neil P; Lewis, David I; Deuchars, Susan A; Deuchars, Jim

    2008-01-16

    Voltage-gated potassium (Kv) channels are essential components of neuronal excitability. The Kv3.4 channel protein is widely distributed throughout the central nervous system (CNS), where it can form heteromeric or homomeric Kv3 channels. Electrophysiological studies reported here highlight a functional role for this channel protein within neurons of the dorsal vagal nucleus (DVN). Current clamp experiments revealed that blood depressing substance (BDS) and intracellular dialysis of an anti-Kv3.4 antibody prolonged the action potential duration. In addition, a BDS sensitive, voltage-dependent, slowly inactivating outward current was observed in voltage clamp recordings from DVN neurons. Electrical stimulation of the solitary tract evoked EPSPs and IPSPs in DVN neurons and BDS increased the average amplitude and decreased the paired pulse ratio, consistent with a presynaptic site of action. This presynaptic modulation was action potential dependent as revealed by ongoing synaptic activity. Given the role of the Kv3 proteins in shaping neuronal excitability, these data highlight a role for homomeric Kv3.4 channels in spike timing and neurotransmitter release in low frequency firing neurons of the DVN.

  1. Blockade of multiple human cardiac potassium currents by the antihistamine terfenadine: possible mechanism for terfenadine-associated cardiotoxicity.

    PubMed

    Crumb, W J; Wible, B; Arnold, D J; Payne, J P; Brown, A M

    1995-01-01

    Use of the antihistamine terfenadine has been associated with QT prolongation and torsade de pointes. One possible mechanism is blockade of cardiac potassium channels. We therefore characterized the effects of terfenadine on potassium currents recorded from isolated human cardiac myocytes. We demonstrated terfenadine block of the transient outward current and a novel, ultra-rapidly activating, delayed rectifier K+ current (IKur), which is very sensitive to 4-aminopyridine. IKur is probably produced by the protein product of Kv1.5a, a Shaker-like potassium channel cDNA cloned from human heart. We also compared terfenadine blockade of fHK (Kv1.5a) currents stably expressed in a human embryonic kidney cell line with terfenadine blockade of IKur in human atrial myocytes. Using the patch-clamp technique, we found that terfenadine produced a time-dependent reduction in Kv1.5a current that was consistent with blockade from the cytoplasmic side of the channel. The terfenadine-sensitive Kv1.5a current in human embryonic kidney cells was similar to the 4-aminopyridine-sensitive current in human atrial myocytes. In addition to blockade of the transient outward current and IKur, terfenadine at clinically relevant concentrations blocked both the rapidly and slowly activating components of the delayed rectifier in human atrial myocytes. Blockade of these K+ currents may contribute to the cardiotoxicity associated with terfenadine usage.

  2. Augmented potassium current is a shared phenotype for two genetic defects associated with familial atrial fibrillation

    PubMed Central

    Abraham, Robert L; Yang, Tao; Blair, Marcia; Roden, Dan M; Darbar, Dawood

    2009-01-01

    Background Mutations in multiple genes have been implicated in familial atrial fibrillation (AF), but the underlying mechanisms, and thus implications for therapy, remain ill-defined. Methods and Results Among 231 participants in the Vanderbilt AF Registry, we found a mutation in KCNQ1 (encoding the α-subunit of slow delayed rectifier potassium current [IKs]) and separately a mutation in natriuretic peptide precursor A (NPPA) gene (encoding atrial natriuretic peptide, ANP), both segregating with early-onset lone AF in different kindreds. The functional effects of these mutations yielded strikingly similar IKs “gain of function.” In Chinese Hamster Ovary (CHO) cells, coexpression of mutant KCNQ1 with its ancillary subunit KCNE1 generated ~3-fold larger currents that activated much faster than wild-type (WT)-IKs. Application of the WT NPPA peptide fragment produced similar changes in WT-IKs, and these were exaggerated with the mutant NPPA S64R peptide fragment. Anantin, a competitive ANP receptor antagonist, completely inhibited the changes in IKs gating observed with NPPA-S64R. Computational simulations identified accelerated transitions into open states as the mechanism for variant IKs gating. Incorporating these IKs changes into computed human atrial action potentials (AP) resulted in 37% shortening (120 vs. 192 ms at 300 ms cycle length), reflecting loss of the phase II dome which is dependent on L-type calcium channel current. Conclusions We found striking functional similarities due to mutations in KCNQ1 and NPPA genes which led to IKs “gain of function”, atrial AP shortening, and consequent altered calcium current as a common mechanism between diverse familial AF syndromes. PMID:19646991

  3. Hypoxia sensitivity of a voltage-gated potassium current in porcine intrapulmonary vein smooth muscle cells.

    PubMed

    Dospinescu, Ciprian; Widmer, Hélène; Rowe, Iain; Wainwright, Cherry; Cruickshank, Stuart F

    2012-09-01

    Hypoxia contracts the pulmonary vein, but the underlying cellular effectors remain unclear. Utilizing contractile studies and whole cell patch-clamp electrophysiology, we report for the first time a hypoxia-sensitive K(+) current in porcine pulmonary vein smooth muscle cells (PVSMC). Hypoxia induced a transient contractile response that was 56 ± 7% of the control response (80 mM KCl). This contraction required extracellular Ca(2+) and was sensitive to Ca(2+) channel blockade. Blockade of K(+) channels by tetraethylammonium chloride (TEA) or 4-aminopyridine (4-AP) reversibly inhibited the hypoxia-mediated contraction. Single-isolated PVSMC (typically 159.1 ± 2.3 μm long) had mean resting membrane potentials (RMP) of -36 ± 4 mV with a mean membrane capacitance of 108 ± 3.5 pF. Whole cell patch-clamp recordings identified a rapidly activating, partially inactivating K(+) current (I(KH)) that was hypoxia, TEA, and 4-AP sensitive. I(KH) was insensitive to Penitrem A or glyburide in PVSMC and had a time to peak of 14.4 ± 3.3 ms and recovered in 67 ms following inactivation at +80 mV. Peak window current was -32 mV, suggesting that I(KH) may contribute to PVSMC RMP. The molecular identity of the potassium channel is not clear. However, RT-PCR, using porcine pulmonary artery and vein samples, identified Kv(1.5), Kv(2.1), and BK, with all three being more abundant in the PV. Both artery and vein expressed STREX, a highly conserved and hypoxia-sensitive BK channel variant. Taken together, our data support the hypothesis that hypoxic inhibition of I(KH) would contribute to hypoxic-induced contraction in PVSMC.

  4. Dopamine modulation of transient potassium current evokes phase shifts in a central pattern generator network.

    PubMed

    Harris-Warrick, R M; Coniglio, L M; Barazangi, N; Guckenheimer, J; Gueron, S

    1995-01-01

    Bath application of dopamine modifies the rhythmic motor pattern generated by the 14 neuron pyloric network in the stomatogastric ganglion of the spiny lobster, Panulirus interruptus. Among other effects, dopamine excites many of the pyloric constrictor (PY) neurons to fire at high frequency and phase-advances the timing of their activity in the motor pattern. These responses arise in part from direct actions of dopamine to modulate the intrinsic electrophysiological properties of the PY cells, and can be studied in synaptically isolated neurons. The rate of rebound following a hyperpolarizing prestep and the spike frequency during a subsequent depolarization are both accelerated by dopamine. Based on theoretical simulations, Hartline (1979) suggested that the rate of postinhibitory rebound in stomatogastric neurons could vary with the amount of voltage-sensitive transient potassium current (IA). Consistent with this prediction, we found that dopamine evokes a net conductance decrease in synaptically isolated PY neurons. In voltage clamp, dopamine reduces IA, specifically by reducing the amplitude of the slowly inactivating component of the current and shifting its voltage activation curve in the depolarized direction. 4-Aminopyridine, a selective blocker of IA in stomatogastric neurons, mimics and occludes the effects of dopamine on isolated PY neurons. A conductance-based mathematical model of the PY neuron shows appropriate changes in activity upon quantitative modification of the IA parameters affected by dopamine. These results demonstrate that dopamine excites and phase-advances the PY neurons in the rhythmic pyloric motor pattern at least in part by reducing the transient K+ current, IA.

  5. Effects of extracellular potassium on ventricular automaticity and evidence for a pacemaker current in mammalian ventricular myocardium.

    PubMed

    Katzung, B G; Morgenstern, J A

    1977-01-01

    Automaticity was induced in isolated guinea pig and cat papillary muscles by application of depolarizing constant current pulses. Increasing extracellular potassium from 1 to 15 mM caused a shift of pacemaker-like activity to less negative diastolic potentials and a decrease in maximum phase 4 slope. Membrane resistance, estimated from the relation of applied current to maximum diastolic potential, decreased when extracellular potassium was increased. Voltage clamps of cat papillary muscle demonstrated that action potentials activate a time-dependent outward current which has a reversal potential of -79.1 mV (+/- 0.99 SE, n = 20) at an extracellular potassium concentration of 5 mM. The reversal potential of this current varies with extracellular K+ with a slope of 50-60 mV per 10-fold concentration change. The current is activated by voltage clamps or action potential plateaus in the range of -30 to +30 mV. It has a time constant of deactivation which increases from approximately 100 to over 400 msec as clamp potential is increased from -90 to -60 mV. It is proposed that this current is equivalent to Ix1 demonstrated in other cardiac tissues and is responsible, in combination with inward currents, for automaticity in ventricular fibers.

  6. A role of stretch-activated potassium currents in the regulation of uterine smooth muscle contraction

    PubMed Central

    Buxton, Iain L O; Heyman, Nathanael; Wu, Yi-ying; Barnett, Scott; Ulrich, Craig

    2011-01-01

    Rates of premature birth are alarming and threaten societies and healthcare systems worldwide. Premature labor results in premature birth in over 50% of cases. Preterm birth accounts for three-quarters of infant morbidity and mortality. Children that survive birth before 34 weeks gestation often face life-long disability. Current treatments for preterm labor are wanting. No treatment has been found to be generally effective and none are systematically evaluated beyond 48 h. New approaches to the treatment of preterm labor are desperately needed. Recent studies from our laboratory suggest that the uterine muscle is a unique compartment with regulation of uterine relaxation unlike that of other smooth muscles. Here we discuss recent evidence that the mechanically activated 2-pore potassium channel, TREK-1, may contribute to contraction-relaxation signaling in uterine smooth muscle and that TREK-1 gene variants associated with human labor and preterm labor may lead to a better understanding of preterm labor and its possible prevention. PMID:21642947

  7. Cyclic AMP enhances calcium-dependent potassium current in Aplysia neurons.

    PubMed

    Ewald, D; Eckert, R

    1983-12-01

    The effect on the Ca-dependent potassium current, IK(Ca), of procedures that increase intracellular cAMP levels was studied in Aplysia neurons using three different pharmacological approaches. Exposure to cAMP analogues which were either resistant to or protected from phosphodiesterase hydrolysis caused an increase in IK(Ca) from 30 to 50% in 10 min. The degree of reversibility of this effect varied from complete with db cAMP to very little with pcpt cAMP. Exposure to cholera toxin, which stimulates the synthesis of endogenous cAMP, increased IK(Ca) 25% in 10 min and the effect was not reversible. Both approaches were effective in all seven neuron types studied. Application of serotonin plus phosphodiesterase inhibitor caused an increase in IK(Ca) in neuron R15 but not in the other neuron types. Application of pentylene tetrazole (PTZ) led to a decrease in IK(Ca). It is proposed that elevation of cyclic AMP mediates an increased sensitivity of the IK(Ca) channel to Ca ions.

  8. Different effects of endothelin-1 on calcium and potassium currents in canine ventricular cells.

    PubMed

    Bányász, T; Magyar, J; Körtvély, A; Szigeti, G; Szigligeti, P; Papp, Z; Mohácsi, A; Kovács, L; Nánási, P P

    2001-04-01

    Effects of endothelin-1 (ET-1) on the L-type calcium current (ICa) and delayed rectifier potassium current (IK) were studied in isolated canine ventricular cardiomyocytes using the whole-cell configuration of the patch-clamp technique. ET-1 (8 nM) was applied in three experimental arrangements: untreated cells, in the presence of 50 nM isoproterenol, and in the presence of 250 microM 8-bromo-cAMP. In untreated cells, ET-1 significantly decreased the peak amplitude of ICa by 32.3+/-4.8% at +5 mV (P<0.05) without changing activation or inactivation characteristics of ICa. ET-1 had no effect on the amplitude of IK, Ito (transient outward current) or IK1 (inward rectifier K current) in untreated cells; however, the time course of recovery from inactivation of Ito was significantly increased by ET-1 (from 26.5+/-4.6 ms to 59.5+/- 1.8 ms, P < 0.05). Amplitude and time course of intracellular calcium transients, recorded in voltage-clamped cells previously loaded with the fluorescent calcium indicator dye Fura-2, were not affected by ET-1. ET-1 had no effect on force of contraction in canine ventricular trabeculae. Isoproterenol increased the amplitude of ICa to 263+/-29% of control. ET-1 reduced ICa also in isoproterenol-treated cells by 17.8+/-2% (P<0.05); this inhibition was significantly less than obtained in untreated cells. IK was increased by isoproterenol to 213+/-18% of control. This effect of isoproterenol on IK was reduced by 31.8+/-4.8% if the cells were pretreated with ET-1. Similarly, in isoproterenol-treated cells ET-1 decreased IK by 16.2+/-1.5% (P<0.05). Maximal activation of protein kinase A (PKA) was achieved by application of 8-bromo-cAMP in the pipette solution. In the presence of 8-bromo-cAMP ET-1 failed to alter ICa or IK It was concluded that differences in effects of ET-1 on ICa and IK may be related to differences in cAMP sensitivity of the currents.

  9. Control of spontaneous firing patterns by the selective coupling of calcium currents to calcium-activated potassium currents in striatal cholinergic interneurons.

    PubMed

    Goldberg, Joshua A; Wilson, Charles J

    2005-11-02

    The spontaneous firing patterns of striatal cholinergic interneurons are sculpted by potassium currents that give rise to prominent afterhyperpolarizations (AHPs). Large-conductance calcium-activated potassium (BK) channel currents contribute to action potential (AP) repolarization; small-conductance calcium-activated potassium channel currents generate an apamin-sensitive medium AHP (mAHP) after each AP; and bursts of APs generate long-lasting slow AHPs (sAHPs) attributable to apamin-insensitive currents. Because all these currents are calcium dependent, we conducted voltage- and current-clamp whole-cell recordings while pharmacologically manipulating calcium channels of the plasma membrane and intracellular stores to determine what sources of calcium activate the currents underlying AP repolarization and the AHPs. The Cav2.2 (N-type) blocker omega-conotoxin GVIA (1 microM) was the only blocker that significantly reduced the mAHP, and it induced a transition to rhythmic bursting in one-third of the cells tested. Cav1 (L-type) blockers (10 microM dihydropyridines) were the only ones that significantly reduced the sAHP. When applied to cells induced to burst with apamin, dihydropyridines reduced the sAHPs and abolished bursting. Depletion of intracellular stores with 10 mM caffeine also significantly reduced the sAHP current and reversibly regularized firing. Application of 1 microM omega-conotoxin MVIIC (a Cav2.1/2.2 blocker) broadened APs but had a negligible effect on APs in cells in which BK channels were already blocked by submillimolar tetraethylammonium chloride, indicating that Cav2.1 (Q-type) channels provide the calcium to activate BK channels that repolarize the AP. Thus, calcium currents are selectively coupled to the calcium-dependent potassium currents underlying the AHPs, thereby creating mechanisms for control of the spontaneous firing patterns of these neurons.

  10. p38 Activation Is Required Upstream of Potassium Current Enhancement and Caspase Cleavage in Thiol Oxidant-Induced Neuronal Apoptosis

    PubMed Central

    McLaughlin, BethAnn; Pal, Sumon; Tran, Minhnga P.; Parsons, Andrew A.; Barone, Frank C.; Erhardt, Joseph A.; Aizenman, Elias

    2013-01-01

    Oxidant-induced neuronal apoptosis has been shown to involve potassium and zinc dysregulation, energetic dysfunction, activation of stress-related kinases, and caspase cleavage. The temporal ordering and interdependence of these events was investigated in primary neuronal cultures exposed to the sulfhydryl oxidizing agent 2,2′-dithiodipyridine (DTDP), a compound that induces the intracellular release of zinc. We previously observed that tetraethylammonium (TEA), high extracellular potassium, or cysteine protease inhibitors block apoptosis induced by DTDP. We now report that both p38 and extracellular signal-regulated kinase phosphorylation are evident in neuronal cultures within 2 hr of a brief exposure to 100 μm DTDP. However, only p38 inhibition is capable of blocking oxidant-induced toxicity. Cyclohexamide or actinomycin D does not attenuate DTDP-induced cell death, suggesting that posttranslational modification of existing targets, rather than transcriptional activation, is responsible for the deleterious effects of p38. Indeed, an early robust increase in TEA-sensitive potassium channel currents induced by DTDP is attenuated by p38 inhibition but not by caspase inhibition. Moreover, we found that activation of p38 is required for caspase 3 and 9 cleavage, suggesting that potassium currents enhancement is required for caspase activation. Finally, we observed that DTDP toxicity could be blocked with niacinamide or benzamide, inhibitors of poly (ADP-ribose) synthetase. Based on these findings, we conclude that oxidation of sulfhydryl groups on intracellular targets results in intracellular zinc release, p38 phosphorylation, enhancement of potassium currents, caspase cleavage, energetic dysfunction, and translationally independent apoptotic cell death. PMID:11331359

  11. Thyroid status and diabetes modulate regional differences in potassium currents in rat ventricle.

    PubMed Central

    Shimoni, Y; Severson, D; Giles, W

    1995-01-01

    1. The rate dependence and recovery kinetics of the Ca(2+)-independent transient (I(t)) and steady-state or 'pedestal' (Iss) outward potassium (K+) currents were studied in single myocytes isolated from epicardial and endocardial regions of rat left ventricles. The whole-cell, suction microelectrode method was used to measure baseline (fully reactivated) I(t), as well as its rate-dependent attenuation. Results from a group of control animals were compared with data from three other groups having an experimentally altered hormonal status. 2. I(t) was significantly smaller in endocardial cells than in epicardial cells, in part due to a very large difference in the recovery kinetics of this current in endocardial cells. This was reflected in a pronounced rate-dependent prolongation of endocardial action potentials. In contrast, the non-inactivating 'pedestal' current, Iss, was very similar in magnitude and showed comparable rate dependence in cells from both epicardium and endocardium. 3. Changing the thyroid status had selective, differential actions on the amplitude and rate dependence of It in epicardial and endocardial cells. Under hypothyroid conditions there was a more pronounced reduction of baseline I(t) in epicardial than in endocardial cells. Moreover, a slowing of the recovery kinetics in epicardial cells resulted in an enhanced attenuation of this current at high rates. Changing thyroid status had no effect on the magnitude or rate dependence of Iss in cells from either region of the left ventricle. 4. Following establishment of hyperthyroid conditions, there was no significant change in I(t) magnitude at baseline. However, when compared with control data, the recovery of I(t) was considerably faster in endocardial cells, and marginally faster in epicardial cells. 5. Streptozotocin-induced diabetic conditions resulted in a much greater attenuation of I(t) in epicardial cells than in endocardial cells. Epicardial action potentials in these conditions showed

  12. Sequential acquisition of cacophony calcium currents, sodium channels and voltage-dependent potassium currents affects spike shape and dendrite growth during postembryonic maturation of an identified Drosophila motoneuron.

    PubMed

    Ryglewski, Stefanie; Kilo, Lukas; Duch, Carsten

    2014-05-01

    During metamorphosis the CNS undergoes profound changes to accommodate the switch from larval to adult behaviors. In Drosophila and other holometabolous insects, adult neurons differentiate either from respecified larval neurons, newly born neurons, or are born embryonically but remain developmentally arrested until differentiation during pupal life. This study addresses the latter in the identified Drosophila flight motoneuron 5. In situ patch-clamp recordings, intracellular dye fills and immunocytochemistry address the interplay between dendritic shape, excitability and ionic current development. During pupal life, changes in excitability and spike shape correspond to a stereotyped, progressive appearance of voltage-gated ion channels. High-voltage-activated calcium current is the first current to appear at pupal stage P4, prior to the onset of dendrite growth. This is followed by voltage-gated sodium as well as transient potassium channel expression, when first dendrites grow, and sodium-dependent action potentials can be evoked by somatic current injection. Sustained potassium current appears later than transient potassium current. During the early stages of rapid dendritic growth, sodium-dependent action potentials are broadened by a calcium component. Narrowing of spike shape coincides with sequential increases in transient and sustained potassium currents during stages when dendritic growth ceases. Targeted RNAi knockdown of pupal calcium current significantly reduces dendritic growth. These data indicate that the stereotyped sequential acquisition of different voltage-gated ion channels affects spike shape and excitability such that activity-dependent calcium influx serves as a partner of genetic programs during critical stages of motoneuron dendrite growth.

  13. Sequential acquisition of cacophony calcium currents, sodium channels and voltage-dependent potassium currents affects spike shape and dendrite growth during postembryonic maturation of an identified Drosophila motoneuron

    PubMed Central

    Ryglewski, Stefanie; Kilo, Lukas; Duch, Carsten

    2015-01-01

    During metamorphosis the CNS undergoes profound changes to accommodate the switch from larval to adult behaviors. In Drosophila and other holometabolous insects, adult neurons differentiate either from respecified larval neurons, newly born neurons, or are born embryonically but remain developmentally arrested until differentiation during pupal life. This study addresses the latter in the identified Drosophila flight motoneuron 5. In situ patch-clamp recordings, intracellular dye fills and immunocytochemistry address the interplay between dendritic shape, excitability and ionic current development. During pupal life, changes in excitability and spike shape correspond to a stereotyped, progressive appearance of voltage-gated ion channels. High-voltage-activated calcium current is the first current to appear at pupal stage P4, prior to the onset of dendrite growth. This is followed by voltage-gated sodium as well as transient potassium channel expression, when first dendrites grow, and sodium-dependent action potentials can be evoked by somatic current injection. Sustained potassium current appears later than transient potassium current. During the early stages of rapid dendritic growth, sodium-dependent action potentials are broadened by a calcium component. Narrowing of spike shape coincides with sequential increases in transient and sustained potassium currents during stages when dendritic growth ceases. Targeted RNAi knockdown of pupal calcium current significantly reduces dendritic growth. These data indicate that the stereotyped sequential acquisition of different voltage-gated ion channels affects spike shape and excitability such that activity-dependent calcium influx serves as a partner of genetic programs during critical stages of motoneuron dendrite growth. PMID:24620836

  14. Sodium and Potassium Currents Influence Wallerian Degeneration of Injured Drosophila Axons

    PubMed Central

    Mishra, Bibhudatta; Carson, Ross; Hume, Richard I.

    2013-01-01

    Axons degenerate after injury and in neuropathies and disease via a self-destruction program whose mechanism is poorly understood. Axons that have lost connection to their cell bodies have altered electrical and synaptic activities, but whether such changes play a role in the axonal degeneration process is not clear. We have used a Drosophila model to study the Wallerian degeneration of motoneuron axons and their neuromuscular junction synapses. We found that degeneration of the distal nerve stump after a nerve crush is greatly delayed when there is increased potassium channel activity (by overexpression of two different potassium channels, Kir2.1 and dORKΔ-C) or decreased voltage-gated sodium channel activity (using mutations in the para sodium channel). Conversely, degeneration is accelerated when potassium channel activity is decreased (by expressing a dominant-negative mutation of Shaker). Despite the effect of altering voltage-gated sodium and potassium channel activity, recordings made after nerve crush demonstrated that the distal stump does not fire action potentials. Rather, a variety of lines of evidence suggest that the sodium and potassium channels manifest their effects upon degeneration through changes in the resting membrane potential, which in turn regulates the level of intracellular free calcium within the isolated distal axon. PMID:24285879

  15. Potassium current kinetics in bursting secretory neurons: effects of intracellular calcium.

    PubMed

    Martínez, J J; Onetti, C G; García, E; Hernández, S

    1991-11-01

    1. The kinetics of delayed rectifier (IK) and transient potassium (IA) currents and their modification by intracellular calcium ions in bursting X-organ neurons of the crayfish were studied with whole-cell patch-clamp technique. Activation and inactivation kinetics were analyzed according to Hodgkin and Huxley-type equations. 2. IK activates with sigmoidal time course at membrane potentials more positive than -38.4 +/- 3.5 (SD) mV (n = 5), and does not inactivate. The conductance through delayed rectifier channels (gK) is described by the equation gK = GKn2. 3. IA activates at membrane potentials close to the resting potential (-52.2 +/- 4.3 mV, n = 5) and, after a peak, inactivates completely. The conductance through A-channels (gA) can be described by the product of independent activation and inactivation parameters: gA = GAa4b. Both activation and inactivation processes are voltage and time dependent. 4. Steady-state activation of IK and IA as well as inactivation of IA can be described by Boltzmann distributions for single particles with valencies of 2.55 +/- 0.01 (n = 5), 1.60 +/- 0.25 (n = 5), and 3.87 +/- 0.39 (n = 3), respectively. 5. Increasing [Ca2+]i, we observed the following: 1) a considerable inactivation of IK during test pulses, 2) an increase of maximal conductance for IA, 3) a reduction of the valency of IA inactivation gating particle (from 3.87 to 2.27), 4) a reduction of the inactivation time constants of IA, and 5) a shift of the inactivation steady-state curve to more positive membrane potentials.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Altered expression and localization of hippocampal A-type potassium channel subunits in the pilocarpine-induced model of temporal lobe epilepsy.

    PubMed

    Monaghan, M M; Menegola, M; Vacher, H; Rhodes, K J; Trimmer, J S

    2008-10-15

    Altered ion channel expression and/or function may contribute to the development of certain human epilepsies. In rats, systemic administration of pilocarpine induces a model of human temporal lobe epilepsy, wherein a brief period of status epilepticus (SE) triggers development of spontaneous recurrent seizures that appear after a latency of 2-3 weeks. Here we investigate changes in expression of A-type voltage-gated potassium (Kv) channels, which control neuronal excitability and regulate action potential propagation and neurotransmitter release, in the pilocarpine model of epilepsy. Using immunohistochemistry, we examined the expression of component subunits of somatodendritic (Kv4.2, Kv4.3, KChIPl and KChIP2) and axonal (Kv1.4) A-type Kv channels in hippocampi of pilocarpine-treated rats that entered SE. We found that Kv4.2, Kv4.3 and KChIP2 staining in the molecular layer of the dentate gyrus changes from being uniformly distributed across the molecular layer to concentrated in just the outer two-thirds. We also observed a loss of KChIP1 immunoreactive interneurons, and a reduction of Kv4.2 and KChIP2 staining in stratum radiatum of CA1. These changes begin to appear 1 week after pilocarpine treatment and persist or are enhanced at 4 and 12 weeks. As such, these changes in Kv channel distribution parallel the acquisition of recurrent spontaneous seizures as observed in this model. We also found temporal changes in Kv1.4 immunoreactivity matching those in Timm's stain, being expanded in stratum lucidum of CA3 and in the inner third of the dentate molecular layer. Among pilocarpine-treated rats, changes were only observed in those that entered SE. These changes in A-type Kv channel expression may contribute to hyperexcitability of dendrites in the associated hippocampal circuits as observed in previous studies of the effects of pilocarpine-induced SE.

  17. Interaction of Kv3 potassium channels and resurgent sodium current influences the rate of spontaneous firing of Purkinje neurons.

    PubMed

    Akemann, Walther; Knöpfel, Thomas

    2006-04-26

    Purkinje neurons spontaneously generate action potentials in the absence of synaptic drive and thereby exert a tonic, yet plastic, input to their target cells in the deep cerebellar nuclei. Purkinje neurons express two ionic currents with biophysical properties that are specialized for high-frequency firing: resurgent sodium currents and potassium currents mediated by Kv3.3. How these ionic currents determine the intrinsic activity of Purkinje neurons has only partially been understood. Purkinje neurons from mutant mice lacking Kv3.3 have a reduced rate of spontaneous firing. Dynamic-clamp recordings demonstrated that normal firing rates are rescued by inserting artificial Kv3 currents into Kv3.3 knock-out Purkinje neurons. Numerical simulations indicated that Kv3.3 increases the spontaneous firing rate via cooperation with resurgent sodium currents. We conclude that the rate of spontaneous action potential firing of Purkinje neurons is controlled by the interaction of Kv3.3 potassium currents and resurgent sodium currents.

  18. Potassium currents dynamically set the recruitment and firing properties of F-type motoneurons in neonatal mice

    PubMed Central

    Lamotte d'Incamps, Boris; Zytnicki, Daniel

    2015-01-01

    In neonatal mice, fast- and slow-type motoneurons display different patterns of discharge. In response to a long liminal current pulse, the discharge is delayed up to several seconds in fast-type motoneurons and their firing frequency accelerates. In contrast, slow-type motoneurons discharge immediately, and their firing frequency decreases at the beginning of the pulse. Here, we identify the ionic currents that underlie the delayed firing of fast-type motoneurons. We find that the firing delay is caused by a combination of an A-like potassium current that transiently suppresses firing on a short time scale and a slowly-inactivating potassium current that inhibits the discharge over a much longer time scale. We then show how these intrinsic currents dynamically shape the discharge threshold and the frequency-input function of fast-type motoneurons. These currents contribute to the orderly recruitment of motoneurons in neonates and might play a role in the postnatal maturation of motor units. PMID:26269551

  19. Effects of cytochrome P450 inhibitors on potassium currents and mechanical activity in rat portal vein.

    PubMed Central

    Edwards, G.; Zygmunt, P. M.; Högestätt, E. D.; Weston, A. H.

    1996-01-01

    1. The effects of the cytochrome P450 inhibitors, proadifen, clotrimazole and 17-octadecynoic acid (17-ODYA) on K-currents in freshly-isolated single cells derived from rat portal vein and on mechanical activity in whole veins were studied. 2. When cells were stepped from -90 mV to a series of test potentials (from -80 to +50 mV), a delayed rectifier current (IK(V)) and an A-type current (IK(A)) could be identified. Proadifen (10 microM), clotrimazole (30 microM) and 17-ODYA (5 microM) each inhibited IK(V) but had little effect on IK(A). 3. When cells were held at -10 mV to inactivate the time-dependent K-currents, IK(V) and IK(A), levcromakalim (3 microM) induced a time-independent outward K-current (IK(ATP)) which was totally inhibited by clotrimazole (30 microM) and almost fully inhibited by proadifen (10 microM). 17-ODYA (5 microM) had no effect on IK(ATP) and exerted only a minor inhibitory action on this current at 20 microM. 4. 17-ODYA (5 microM) potentiated current flow through the large conductance, Ca-sensitive K-channel (BKCa). In contrast, proadifen (10 microM) had no effect on IBK(Ca) whereas clotrimazole (30 microM) exerted a small but significant inhibitory action. 5. Proadifen (10 microM) and clotrimazole (30 microM) each inhibited the magnitude but increased the frequency of spontaneous contractions in whole portal veins. 17-ODYA (5 microM) had no effect on spontaneous contractions but these were inhibited when the concentration of 17-ODYA was increased to 50 microM. 6. The spasmolytic effect of levcromakalim on spontaneous contractions was antagonized by proadifen (10-30 microM) in a concentration-dependent manner but 17-ODYA (up to 50 microM) was without effect. 7. These results in portal vein show that cytochrome P450 inhibitors exert profound effects on a variety of K-channel subtypes. This suggests that enzymes dependent on this cofactor may be important regulators of K-channel activity in smooth muscle. The relevance of these findings for the

  20. Altered Expression and Localization of Hippocampal A-Type Potassium Channel Subunits in the Pilocarpine-Induced Model of Temporal Lobe Epilepsy

    PubMed Central

    Monaghan, Michael M.; Menegola, Milena; Vacher, Helene; Rhodes, Kenneth J.; Trimmer, James S.

    2010-01-01

    Summary Altered ion channel expression and/or function may contribute to the development of certain human epilepsies. In rats, systemic administration of pilocarpine induces a model of human temporal lobe epilepsy, wherein a brief period of status epilepticus (SE) triggers development of spontaneous recurrent seizures that appear after a latency of two-three weeks. Here we investigate changes in expression of A-type voltage-gated potassium (Kv) channels, which control neuronal excitability and regulate action potential propagation and neurotransmitter release, in the pilocarpine model of epilepsy. Using immunohistochemistry, we examined the expression of component subunits of somatodendritic (Kv4.2, Kv4.3, KChIPl and KChIP2) and axonal (Kv1.4) A-type Kv channels in hippocampi of pilocarpine-treated rats that entered SE. We found that Kv4.2, Kv4.3 and KChIP2 staining in the molecular layer of the dentate gyrus changes from being uniformly distributed across the molecular layer to concentrated in just the outer two-thirds. We also observed a loss of KChIP1 immunoreactive interneurons, and a reduction of Kv4.2 and KChIP2 staining in stratum radiatum of CA1. These changes begin to appear 1 week after pilocarpine treatment and persist or are enhanced at 4 and 12 weeks. As such, these changes in Kv channel distribution parallel the acquisition of recurrent spontaneous seizures as observed in this model. We also found temporal changes in Kv1.4 immunoreactivity matching those in Timm's stain, being expanded in stratum lucidum of CA3 and in the inner third of the dentate molecular layer. Among pilocarpine-treated rats, changes were only observed in those that entered SE. These changes in A-type Kv channel expression may contribute to hyperexcitability of dendrites in the associated hippocampal circuits as observed in previous studies of the effects of pilocarpine-induced SE. PMID:18727953

  1. Ethanol effects on dopaminergic ventral tegmental area neurons during block of Ih: involvement of barium-sensitive potassium currents.

    PubMed

    McDaid, John; McElvain, Maureen A; Brodie, Mark S

    2008-09-01

    The dopaminergic neurons of the ventral tegmental area (DA VTA neurons) are important for the rewarding and reinforcing properties of drugs of abuse, including ethanol. Ethanol increases the firing frequency of DA VTA neurons from rats and mice. Because of a recent report on block of ethanol excitation in mouse DA VTA neurons with ZD7288, a selective blocker of the hyperpolarization-activated cationic current Ih, we examined the effect of ZD7288 on ethanol excitation in DA VTA neurons from C57Bl/6J and DBA/2J mice and Fisher 344 rats. Ethanol (80 mM) caused only increases in firing rate in mouse DA VTA neurons in the absence of ZD7288, but in the presence of ZD7288 (30 microM), ethanol produced a more transient excitation followed by a decrease of firing. This same biphasic phenomenon was observed in DA VTA neurons from rats in the presence of ZD7288 only at very high ethanol concentrations (160-240 mM) but not at lower pharmacologically relevant concentrations. The longer latency ethanol-induced inhibition was not observed in DA VTA neurons from mice or rats in the presence of barium (100 microM), which blocks G protein-linked potassium channels (GIRKs) and other inwardly rectifying potassium channels. Ethanol may have a direct effect to increase an inhibitory potassium conductance, but this effect of ethanol can only decrease the firing rate if Ih is blocked.

  2. Sustained upregulation in embryonic spinal neurons of a Kv3.1 potassium channel gene encoding a delayed rectifier current.

    PubMed

    Gurantz, D; Lautermilch, N J; Watt, S D; Spitzer, N C

    2000-02-15

    Differentiation of electrical excitability entails changes in the currents that generate action potentials in spinal neurons of Xenopus embryos, resulting in reduced calcium entry during impulses generated at later stages of development. A dramatic increase in delayed rectifier current (I(Kv)) during the first day of development plays the major role in this process. Identification of potassium channel genes responsible for the increase in I(Kv) is critical to understanding the molecular mechanisms involved. Several members of the Shaw Kv3 gene subfamily encode delayed rectifier currents, indicating that they could contribute to the upregulation of I(Kv) that reduces the duration of action potentials. We isolated a Xenopus (x) Kv3.1 gene whose expression is restricted to the central nervous system, which is upregulated throughout the period during which I(Kv) develops in vivo. The fraction of neurons in which transcripts of this gene are detected by single-cell RT-PCR increases to 40% with time in culture, paralleling the development of I(Kv) in neurons in vitro. Expression of xKv3.1 mRNA generates a delayed rectifier potassium current in oocytes, suggesting that xKv3. 1 contributes to the maturation of I(Kv) and shortening of the action potential.

  3. A novel large-conductance Ca(2+)-activated potassium channel and current in nerve terminals of the rat neurohypophysis.

    PubMed Central

    Wang, G; Thorn, P; Lemos, J R

    1992-01-01

    1. Nerve terminals of the rat posterior pituitary were acutely dissociated and identified using a combination of morphological and immunohistochemical techniques. Terminal membrane currents were studied using the 'whole-cell' patch clamp technique and channels were studied using inside-out and outside-out patches. 2. In physiological solutions, but with 7 mM 4-aminopyridine (4-AP), depolarizing voltage clamp steps from different holding potentials (-90 or -50 mV) elicited a fast, inward current followed by a slow, sustained, outward current. This outward current did not appear to show any steady-state inactivation. 3. The threshold for activation of the outward current was -30 mV and the current-voltage relation was 'bell-shaped'. The amplitude increased with increasingly depolarized potential steps. The outward current reversal potential was measured using tail current analysis and was consistent with that of a potassium current. 4. The sustained potassium current was determined to be dependent on the concentration of intracellular calcium. Extracellular Cd2+ (80 microM), a calcium channel blocker, also reversibly abolished the outward current. 5. The current was delayed in onset and was sustained over the length of a 150 ms-duration depolarizing pulse. The outward current reached a peak plateau and then decayed slowly. The decay was fitted by a single exponential with a time constant of 9.0 +/- 2.2 s. The decay constants did not show a dependence on voltage but rather on intracellular Ca2+. The time course of recovery from this decay was complex with full recovery taking > 190 s. 6. 4-AP (7 mM), dendrotoxin (100 nM), apamin (40-80 nM), and charybdotoxin (10-100 nM) had no effect on the sustained outward current. In contrast Ba2+ (200 microM) and tetraethylammonium inhibited the current, the latter in a dose-dependent manner (apparent concentration giving 50% of maximal inhibition (IC50) = 0.51 mM). 7. The neurohypophysial terminal outward current recorded here

  4. Loss of functional A-type potassium channels in the dendrites of CA1 pyramidal neurons from a mouse model of fragile X syndrome.

    PubMed

    Routh, Brandy N; Johnston, Daniel; Brager, Darrin H

    2013-12-11

    Despite the critical importance of voltage-gated ion channels in neurons, very little is known about their functional properties in Fragile X syndrome: the most common form of inherited cognitive impairment. Using three complementary approaches, we investigated the physiological role of A-type K(+) currents (I(KA)) in hippocampal CA1 pyramidal neurons from fmr1-/y mice. Direct measurement of I(KA) using cell-attached patch-clamp recordings revealed that there was significantly less I(KA) in the dendrites of CA1 neurons from fmr1-/y mice. Interestingly, the midpoint of activation for A-type K(+) channels was hyperpolarized for fmr1-/y neurons compared with wild-type, which might partially compensate for the lower current density. Because of the rapid time course for recovery from steady-state inactivation, the dendritic A-type K(+) current in CA1 neurons from both wild-type and fmr1-/y mice is likely mediated by K(V)4 containing channels. The net effect of the differences in I(KA) was that back-propagating action potentials had larger amplitudes producing greater calcium influx in the distal dendrites of fmr1-/y neurons. Furthermore, CA1 pyramidal neurons from fmr1-/y mice had a lower threshold for LTP induction. These data suggest that loss of I(KA) in hippocampal neurons may contribute to dendritic pathophysiology in Fragile X syndrome.

  5. Loss of Functional A-Type Potassium Channels in the Dendrites of CA1 Pyramidal Neurons from a Mouse Model of Fragile X Syndrome

    PubMed Central

    Routh, Brandy N.; Johnston, Daniel

    2013-01-01

    Despite the critical importance of voltage-gated ion channels in neurons, very little is known about their functional properties in Fragile X syndrome: the most common form of inherited cognitive impairment. Using three complementary approaches, we investigated the physiological role of A-type K+ currents (IKA) in hippocampal CA1 pyramidal neurons from fmr1-/y mice. Direct measurement of IKA using cell-attached patch-clamp recordings revealed that there was significantly less IKA in the dendrites of CA1 neurons from fmr1-/y mice. Interestingly, the midpoint of activation for A-type K+ channels was hyperpolarized for fmr1-/y neurons compared with wild-type, which might partially compensate for the lower current density. Because of the rapid time course for recovery from steady-state inactivation, the dendritic A-type K+ current in CA1 neurons from both wild-type and fmr1-/y mice is likely mediated by KV4 containing channels. The net effect of the differences in IKA was that back-propagating action potentials had larger amplitudes producing greater calcium influx in the distal dendrites of fmr1-/y neurons. Furthermore, CA1 pyramidal neurons from fmr1-/y mice had a lower threshold for LTP induction. These data suggest that loss of IKA in hippocampal neurons may contribute to dendritic pathophysiology in Fragile X syndrome. PMID:24336711

  6. Quantitative analysis of voltage-gated potassium currents from primary equine (Equus caballus) and elephant (Loxodonta africana) articular chondrocytes.

    PubMed

    Mobasheri, A; Gent, T C; Womack, M D; Carter, S D; Clegg, P D; Barrett-Jolley, R

    2005-07-01

    In this comparative study, we have established in vitro models of equine and elephant articular chondrocytes, examined their basic morphology, and characterized the biophysical properties of their primary voltage-gated potassium channel (Kv) currents. Using whole cell patch-clamp electrophysiological recording from first-expansion and first-passage cells, we measured a maximum Kv conductance of 0.15 +/- 0.04 pS/pF (n = 10) in equine chondrocytes, whereas that in elephant chondrocytes was significantly larger (0.8 +/- 0.4 pS/pF, n = 4, P currents had similar activation and inactivation parameters. Pharmacological investigation of equine chondrocyte Kv currents showed them to be powerfully inhibited by the potassium channel blockers tetraethylammonium and 4-aminopyridine but not by dendrotoxin-I. Immunohistochemical studies using polyclonal antibodies to Kv1.1-Kv1.5 provided evidence for expression of Kv1.4 in equine chondrocytes. This is the first electrophysiological study of equine or elephant chondrocytes. The data support the notion that voltage-gated potassium channels play an important role in regulating the membrane potential of articular chondrocytes and will prove useful in future modeling of electromechanotransduction of fully differentiated articular chondrocytes in these and other species.

  7. Long-term effects of prior heat shock on neuronal potassium currents recorded in a novel insect ganglion slice preparation.

    PubMed

    Ramirez, J M; Elsen, F P; Robertson, R M

    1999-02-01

    Brief exposure to high temperatures (heat shock) induces long-lasting adaptive changes in the molecular biology of protein interactions and behavior of poikilotherms. However, little is known about heat shock effects on neuronal properties. To investigate how heat shock affects neuronal properties we developed an insect ganglion slice from locusts. The functional integrity of neuronal circuits in slices was demonstrated by recordings from rhythmically active respiratory neurons and by the ability to induce rhythmic population activity with octopamine. Under these "functional" in vitro conditions we recorded outward potassium currents from neurons of the ventral midline of the A1 metathoracic neuromere. In control neurons, voltage steps to 40 mV from a holding potential of -60 mV evoked in control neurons potassium currents with a peak current of 10.0 +/- 2.5 nA and a large steady state current of 8.5 +/- 2.6 nA, which was still activated from a holding potential of -40 mV. After heat shock most of the outward current inactivated rapidly (peak amplitude: 8.4 +/- 2.4 nA; steady state: 3.6 +/- 2.0 nA). This current was inactivated at a holding potential of -40 mV. The response to temperature changes was also significantly different. After changing the temperature from 38 to 42 degrees C the amplitude of the peak and steady-state current was significantly lower in neurons obtained from heat-shocked animals than those obtained from controls. Our study indicates that not only heat shock can alter neuronal properties, but also that it is possible to investigate ion currents in insect ganglion slices.

  8. Effect of capsaicin and analogues on potassium and calcium currents and vanilloid receptors in Xenopus embryo spinal neurones.

    PubMed Central

    Kuenzi, F. M.; Dale, N.

    1996-01-01

    1. The potassium current in embryo spinal neurones of Xenopus consists of at least two kinetically distinct components with overlapping voltage-dependencies of activation. We investigated whether capsaicin might specifically block these components in acutely dissociated neurones from stage 37/38 embryos by use of standard patch clamp techniques. 2. Capsaicin caused a time-dependent block of both the slow and fast components of the potassium current. The concentration-dependence was described by the Hill equation with a KD of 21 microM and a coefficient of 1.5 (n = 9-11 at each concentration). Differences between the observed and fitted values were not significant at the 5% level (chi(2) = 2.80, 6 degrees of freedom). 3. Capsaicin did not affect the time course or voltage-sensitivity of activation, but the steady-state block was voltage-dependent. The block could be relieved by hyperpolarization, and the rate of the removal of block was voltage- and time-dependent. The time constant for the blocking reaction was also voltage-dependent for voltage steps below +30 mV, but above this level it was voltage-independent. These results suggest that capsaicin blocks potassium channels by an open channel mechanism. 4. Other derivatives of vanillin, such as capsazepine, resiniferatoxin, and piperine also blocked potassium channels. Capsazepine and resiniferatoxin caused a greater block than similar concentrations of capsaicin, and in the case of capsazepine, the block was also clearly time-dependent. 5. Capsaicin and capsazepine also blocked calcium currents in a time-dependent manner. Fitting the Hill equation to the averaged data gave a KD of 43.5 microM, and a coefficient of 1.35 (n = 11 at each concentration). The fitted values were not significantly different from the observed means at the 5% level (chi(2) = 12.1, 6 degrees of freedom). 6. Six out of 29 Rohon-Beard sensory neurones responded to capsaicin with an inward current that appeared to be similar to the capsaicin

  9. The Outwardly Rectifying Current of Layer 5 Neocortical Neurons that was Originally Identified as “Non-Specific Cationic” Is Essentially a Potassium Current

    PubMed Central

    Revah, Omer; Libman, Lior; Fleidervish, Ilya A.; Gutnick, Michael J.

    2015-01-01

    In whole-cell patch clamp recordings from layer 5 neocortical neurons, blockade of voltage gated sodium and calcium channels leaves a cesium current that is outward rectifying. This current was originally identified as a “non-specific cationic current”, and subsequently it was hypothesized that it is mediated by TRP channels. In order to test this hypothesis, we used fluorescence imaging of intracellular sodium and calcium indicators, and found no evidence to suggest that it is associated with influx of either of these ions to the cell body or dendrites. Moreover, the current is still prominent in neurons from TRPC1-/- and TRPC5-/- mice. The effects on the current of various blocking agents, and especially its sensitivity to intracellular tetraethylammonium, suggest that it is not a non-specific cationic current, but rather that it is generated by cesium-permeable delayed rectifier potassium channels. PMID:26197082

  10. Bradykinin modulates potassium and calcium currents in neuroblastoma hybrid cells via different pertussis toxin-insensitive pathways.

    PubMed

    Wilk-Blaszczak, M A; Gutowski, S; Sternweis, P C; Belardetti, F

    1994-01-01

    In NG108-15 cells, bradykinin (BK) activates a potassium current (IK,BK) and inhibits the voltage-dependent calcium current (ICa,V). BK also stimulates a phosphatidylinositol-specific phospholipase C (PI-PLC). The subsequent release of inositol 1,4,5-trisphosphate and increase in intracellular calcium contribute to IK,BK, through activation of a calcium-dependent potassium current. In membranes from these cells, stimulation of PI-PLC by BK is mediated by Gq and/or G11, two homologous, pertussis toxin-insensitive G proteins. Here, we have investigated the role of Gq/11 in the electrical responses to BK. GTP gamma S mimicked and occluded both actions of BK, and both effects were insensitive to pertussis toxin. Perfusion of an anti-Gq/11 alpha antibody into the pipette suppressed IK,BK, but not the inhibition of ICa,V by BK. Thus, BK couples to IK,BK via Gq/11, but coupling to ICa,V is most likely via a different, pertussis toxin-insensitive G protein.

  11. Control of Spontaneous Firing Patterns by the Selective Coupling of Calcium Currents to Calcium Activated Potassium Currents in Striatal Cholinergic Interneurons

    PubMed Central

    Goldberg, Joshua A.; Wilson, Charles J.

    2005-01-01

    The spontaneous firing patterns of striatal cholinergic interneurons are sculpted by potassium currents that give rise to prominent afterhyperpolarizations (AHPs): BK currents contribute to action potential (AP) repolarization; SK currents generate an apamin-sensitive medium AHP (mAHP) following each AP; and bursts of APs generate long-lasting slow AHPs (sAHPs) due to apamin-insensitive currents. As all these currents are calcium-dependent, we conducted voltage- and current-clamp whole-cell recordings while pharmacologically manipulating calcium channels of the plasma membrane and intracellular stores to determine what sources of calcium activate the currents underlying AP repolarization and the AHPs. The Cav2.2 (N type) blocker, omega-conotoxin GVIA (1 μM), was the only blocker that significantly reduced the mAHP, and it induced a transition to rhythmic bursting in a third of the cells tested. Cav1 (L type) blockers (10 μM dihydropyridines) were the only ones that significantly reduced the sAHP. When applied to cells induced to burst with apamin, dihydropyridines reduced the sAHPs and abolished bursting. Depletion of intracellular stores with 10 mM caffeine also significantly reduced the sAHP current, and reversibly regularized firing. Application of 1 μM omega-conotoxin MVIIC (a Cav2.1/2.2 blocker) broadened APs, but had a negligible effect on APs in cells whose BK channels were already blocked by submillimolar tetraethylammonium chloride, indicating that Cav2.1 (Q type) channels provide the calcium to activate BK channels that repolarize the AP. Thus, calcium currents are selectively coupled to the calcium-dependent potassium currents underlying the AHPs thereby creating mechanisms for control of these neurons’ spontaneous firing patterns. PMID:16267230

  12. 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

  13. Contribution of presynaptic calcium-activated potassium currents to transmitter release regulation in cultured Xenopus nerve-muscle synapses.

    PubMed

    Pattillo, J M; Yazejian, B; DiGregorio, D A; Vergara, J L; Grinnell, A D; Meriney, S D

    2001-01-01

    Using Xenopus nerve-muscle co-cultures, we have examined the contribution of calcium-activated potassium (K(Ca)) channels to the regulation of transmitter release evoked by single action potentials. The presynaptic varicosities that form on muscle cells in these cultures were studied directly using patch-clamp recording techniques. In these developing synapses, blockade of K(Ca) channels with iberiotoxin or charybdotoxin decreased transmitter release by an average of 35%. This effect would be expected to be caused by changes in the late phases of action potential repolarization. We hypothesize that these changes are due to a reduction in the driving force for calcium that is normally enhanced by the local hyperpolarization at the active zone caused by potassium current through the K(Ca) channels that co-localize with calcium channels. In support of this hypothesis, we have shown that when action potential waveforms were used as voltage-clamp commands to elicit calcium current in varicosities, peak calcium current was reduced only when these waveforms were broadened beginning when action potential repolarization was 20% complete. In contrast to peak calcium current, total calcium influx was consistently increased following action potential broadening. A model, based on previously reported properties of ion channels, faithfully reproduced predicted effects on action potential repolarization and calcium currents. From these data, we suggest that the large-conductance K(Ca) channels expressed at presynaptic varicosities regulate transmitter release magnitude during single action potentials by altering the rate of action potential repolarization, and thus the magnitude of peak calcium current.

  14. The slow calcium-dependent potassium current in a myenteric neurone of the guinea-pig ileum.

    PubMed

    Hirst, G D; Johnson, S M; van Helden, D F

    1985-04-01

    Experiments were performed in current-clamped and voltage-clamped after-hyperpolarizing (AH) neurones of the guinea-pig myenteric plexus to examine the properties of the potassium conductance (gK, Ca) underlying the slow calcium-activated after-hyperpolarization (VK, Ca). The action potential plateau lengthened by the addition of tetraethylammonium chloride (TEA) to the bathing medium was compared to VK, Ca. Results were consistent with enhanced calcium entry causing an increase of VK, Ca. 4-Aminopyridine (4-AP) directly reduced VK, Ca. Voltage-clamp data of gK, Ca were well fitted by a process with a delay (approximately equal to 60 ms) followed by exponential activation (time constant approximately equal to 300 ms) and inactivation (time constant approximately equal to 2 s). The presence of a small, much slower inactivating process was noted. Values for time constants were similar to those reported by Morita, North & Tokimasa (1982) and North & Tokimasa (1983) where gK, Ca was measured during VK, Ca subsequent to action potential stimulation. The relation between gK, Ca (or the calcium-activated potassium current IK, Ca) and estimated calcium influx resulting from short-duration calcium currents elicited at various voltages was compared. Both the integral of the calcium current and gK, Ca showed a similar dependence on the depolarizations used to elicit IK, Ca except there was a positive shift of about 4 mV for the gK, Ca curve. This shift was attributed to a requirement for calcium ions to prime the gK, Ca mechanism. An inward ion charge movement of about 8 pC was required before significant activation of gK, Ca occurred. After the 'priming' condition had been established, the sensitivity of gK, Ca to inward calcium current measured at the resting potential was about 500 pS/pC of inward charge. Large calcium entry obtained by prolonged calcium currents caused saturation of the peak amplitude of IK, Ca and initiated currents with slower time to peak amplitude and

  15. Calcium and potassium currents in muscle fibres of an insect (Carausius morosus).

    PubMed Central

    Ashcroft, F M; Stanfield, P R

    1982-01-01

    1. A three electrode voltage-clamp was used to investigate membrane currents in the skeletal muscle fibres of the stick insect, Carausius morosus. Contraction was blocked by hypertonic solutions. 2. Membrane currents elicited by step depolarizations consisted of an inward current, an early outward current and a delayed outward current. 3. The reversal potential of the delayed outward current did not change when SO4(2-) was substituted for Cl-, but shifted by 14.1 mV when [K]0 was increased from 20 mM to 40 mM in SO4(2-) solution, suggesting that the delayed current is carried by K+. Both early and delayed outward currents were substantially reduced by 120 mM-tetraethylammonium (TEA) ions. 4. The small size of the shift in the reversal potential of the delayed outward current with increased pulse duration suggests that the delayed current measured flows mainly across the surface membrane. 5. Increasing [Ca]o made the apparent reversal potential for the inward current (120 mM-TEA Ringer) more positive and increased the size of the maximum inward current. However, Ca-currents showed saturation with increasing [Ca]o, indicating that there is a site to which Ca ions bind during their passage through the membrane. The dissociation constant of this site was 7.3 mM at 0 mV and was voltage-dependent. 6. Inward currents were blocked by 1 mM-La3+ or Cd2+, or by substitution of Co2+ or Ni2+ for Mg2+. Strontium and barium were able to permeate the channel but Na+ and Mg2+ appear impermeant. 7. As expected from the low intracellular Ca concentration, the instantaneous current-voltage relation of the Ca current rectified strongly in the inward direction. 8. Both constant field theory and the simplest, single site, Eyring rate theory model predict the rectification of the instantaneous current-voltage relation. The rate theory model also predicts saturation of the Ca current with [Ca]o. PMID:6284919

  16. Calcium and potassium currents in muscle fibres of an insect (Carausius morosus).

    PubMed

    Ashcroft, F M; Stanfield, P R

    1982-02-01

    1. A three electrode voltage-clamp was used to investigate membrane currents in the skeletal muscle fibres of the stick insect, Carausius morosus. Contraction was blocked by hypertonic solutions. 2. Membrane currents elicited by step depolarizations consisted of an inward current, an early outward current and a delayed outward current. 3. The reversal potential of the delayed outward current did not change when SO4(2-) was substituted for Cl-, but shifted by 14.1 mV when [K]0 was increased from 20 mM to 40 mM in SO4(2-) solution, suggesting that the delayed current is carried by K+. Both early and delayed outward currents were substantially reduced by 120 mM-tetraethylammonium (TEA) ions. 4. The small size of the shift in the reversal potential of the delayed outward current with increased pulse duration suggests that the delayed current measured flows mainly across the surface membrane. 5. Increasing [Ca]o made the apparent reversal potential for the inward current (120 mM-TEA Ringer) more positive and increased the size of the maximum inward current. However, Ca-currents showed saturation with increasing [Ca]o, indicating that there is a site to which Ca ions bind during their passage through the membrane. The dissociation constant of this site was 7.3 mM at 0 mV and was voltage-dependent. 6. Inward currents were blocked by 1 mM-La3+ or Cd2+, or by substitution of Co2+ or Ni2+ for Mg2+. Strontium and barium were able to permeate the channel but Na+ and Mg2+ appear impermeant. 7. As expected from the low intracellular Ca concentration, the instantaneous current-voltage relation of the Ca current rectified strongly in the inward direction. 8. Both constant field theory and the simplest, single site, Eyring rate theory model predict the rectification of the instantaneous current-voltage relation. The rate theory model also predicts saturation of the Ca current with [Ca]o.

  17. A calcium-dependent potassium current is increased by a single-gene mutation in Paramecium.

    PubMed

    Hennessey, T M; Kung, C

    1987-01-01

    The membrane currents of wild type Paramecium tetraurelia and the behavioral mutant teaA were analyzed under voltage clamp. The teaA mutant was shown to have a greatly increased outward current which was blocked completely by the combined use of internally delivered Cs+ and external TEA+. This, along with previous work (Satow, Y., Kung, C., 1976, J. Exp. Biol. 65:51-63) identified this as a K+ current. It was further found to be a calcium-activated K+ current since this increased outward K+ current cannot be elicited when the internal calcium is buffered with injected EGTA. The mutation pwB, which blocks the inward calcium current, also blocks this increased outward K+ current in teaA. This shows that this mutant current is activated by calcium through the normal depolarization-sensitive calcium channel. While tail current decay kinetic analysis showed that the apparent inactivation rates for this calcium-dependent K+ current are the same for mutant and wild type, the teaA current activates extremely rapidly. It is fully activated within 2 msec. This early activation of such a large outward current causes a characteristic reduction in the amplitude of the action potential of the teaA mutant. The teaA mutation had no effect on any of the other electrophysiological parameters examined. The phenotype of the teaA mutant is therefore a general decrease in responsiveness to depolarizing stimuli because of a rapidly activating calcium-dependent K+ current which prematurely repolarizes the action potential.

  18. A Drosophila mutation that eliminates a calcium-dependent potassium current.

    PubMed

    Elkins, T; Ganetzky, B; Wu, C F

    1986-11-01

    A mutation of Drosophila, slowpoke (slo), specifically abolishes a Ca2+-dependent K+ current, IC, from dorsal longitudinal flight muscles of adult flies. Other K+ currents remain normal, providing evidence that IC is mediated by a molecularly distinguishable set of channels. The pharmacological properties of IC are similar to those of Ca2+-dependent currents in some vertebrate cells. The muscle action potential was significantly lengthened in slo flies, indicating that IC plays the major role in its repolarization.

  19. Acetaldehyde at clinically relevant concentrations inhibits inward rectifier potassium current I(K1) in rat ventricular myocytes.

    PubMed

    Bébarová, M; Matejovič, P; Šimurdová, M; Šimurda, J

    2015-01-01

    Considering the effects of alcohol on cardiac electrical behavior as well as the important role of the inward rectifier potassium current I(K1) in arrhythmogenesis, this study was aimed at the effect of acetaldehyde, the primary metabolite of ethanol, on I(K1) in rat ventricular myocytes. Acetaldehyde induced a reversible inhibition of I(K1) with IC(50) = 53.7+/-7.7 microM at -110 mV; a significant inhibition was documented even at clinically-relevant concentrations (at 3 microM by 13.1+/-3.0 %). The inhibition was voltage-independent at physiological voltages above -90 mV. The I(K1) changes under acetaldehyde may contribute to alcohol-induced alterations of cardiac electrophysiology, especially in individuals with a genetic defect of aldehyde dehydrogenase where the acetaldehyde level may be elevated.

  20. Correlation character of ionic current fluctuations: analysis of ion current through a voltage-dependent potassium single channel.

    PubMed

    Tong-Han, Lan; Huang, Xi; Jia-Rui, Lin

    2005-10-03

    The gating of ion channels has widely been modeled by assuming the transition between open and closed states is a memoryless process. Nevertheless, the statistical analysis of an ionic current signal recorded from voltage dependence K(+) single channel is presented. Calculating the sample auto-correlation function of the ionic current based on the digitized signals, rather than the sequence of open and closed states duration time. The results provide evidence for the existence of memory. For different voltages, the ion channel current fluctuation has different correlation attributions. The correlations in data generated by simulation of two Markov models, on one hand, auto-correlation function of the ionic current shows a weaker memory, after a delayed period of time, the attribute of memory does not exist; on the other hand, the correlation depends on the number of states in the Markov model. For V(p)=-60 mV pipette potential, spectral analysis of ion channel current was conducted, the result indicates that the spectrum is not a flat spectrum, the data set from ionic current fluctuations shows considerable variability with a broad 1/f -like spectrum, alpha=1.261+/-0.24. Thus the ion current fluctuations give information about the kinetics of the channel protein, the results suggest the correlation character of ion channel protein nonlinear kinetics regardless of whether the channel is in open or closed state.

  1. Synthetic undecapeptide (NTX10-20) of noxiustoxin blocks completely the I(A) potassium currents of cerebellum granular cells.

    PubMed

    Frau, A; Pisciotta, M; Gurrola, G B; Possani, L D; Prestipino, G

    2001-01-01

    Native noxiustoxin (NTX) and synthetic peptides corresponding to its primary sequence, from positions 1-9, 1-14, 1-20, 10-20, 21-39 and 30 39, were prepared and assayed on the K+ currents of cerebellum granular cells, using the patch-clamp technique in the whole-cell configuration system. Native toxin has a reversible inhibitory effect (IC50 = 360 nM), whereas synthetic peptides NTXI-20 and NTX1-9 had a half-effective dose IC50 of approximately 2 and 10 microM, respectively, which correlates with their biological effects in vivo. Synthetic peptide NTX10-20 was quite remarkable in having a preference for the IA current, which was completely inhibited at high peptide concentration. The effects of the other peptides (NTXI 14, NTX21-39 and NTX30-39), although positive and reversible, required higher concentrations (50 200 microM) to block both currents, suggesting no affinity or, at least, much lower specificity for the channels responsible for the potassium currents in the granular cells studied.

  2. Properties of potassium currents in Purkinje cells of failing human hearts.

    PubMed

    Han, Wei; Zhang, Liming; Schram, Gernot; Nattel, Stanley

    2002-12-01

    Cardiac Purkinje fibers play an important role in cardiac arrhythmias, but no information is available about ionic currents in human cardiac Purkinje cells (PCs). PCs and midmyocardial ventricular myocytes (VMs) were isolated from explanted human hearts. K(+) currents were evaluated at 37 degrees C with whole cell patch clamp. PCs had clear inward rectifier K(+) current (I(K1)), with a density not significantly different from VMs between -110 and -20 mV. A Cs(+)-sensitive, time-dependent hyperpolarization-activated current was measurable negative to -60 mV. Transient outward current (I(to)) density was smaller, but end pulse sustained current (I(sus)) was larger, in PCs vs. VMs. I(to) recovery was substantially slower in PCs, leading to strong frequency dependence. Unlike VM I(to), which was unaffected by 10 mM tetraethylammonium, Purkinje I(to) was strongly inhibited by tetraethylammonium, and Purkinje I(to) was 10-fold more sensitive to 4-aminopyridine than VM. PC I(sus) was also reduced strongly by 10 mM tetraethylammonium. In conclusion, human PCs demonstrate a prominent I(K1), a time-dependent hyperpolarization-activated current, and an I(to) with pharmacological sensitivity and recovery kinetics different from those in the atrium or ventricle and compatible with a different molecular basis.

  3. Inactivation of a high conductance calcium dependent potassium current in rat hippocampal neurons.

    PubMed

    McLarnon, J G

    1995-06-23

    Inactivating, high conductance BK-type currents have been recorded from inside-out patches (internal and external K+ of 140 mM and 5 mM, respectively), obtained from cultured rat hippocampal neurons. The presence of prominent inactivation, not normally associated with BK channel activity, was dependent on two factors: a depolarizing step to 0 mV from a holding level of -80 mV and internal calcium at a concentration of 0.7 microM. Without the prior conditioning step to a negative potential, unitary currents were not evident at 0 mV; in addition, such currents were not elicited with the stimulus protocol if the internal Ca2+ was reduced to a level of 0.3 microM. Concomitant with current inactivation was the finding of a delayed activation of BK currents following the depolarizing step. Higher internal calcium, at 100 microM, led to persistent and sustained channel activity at 0 mV which was not dependent on a prior step to -80 mV. These results may be relevant to the complex nature of the repolarizing neuronal current Ic which is the macroscopic analogue of the unitary BK current.

  4. Kv2 subunits underlie slowly inactivating potassium current in rat neocortical pyramidal neurons

    PubMed Central

    Guan, D; Tkatch, T; Surmeier, D J; Armstrong, W E; Foehring, R C

    2007-01-01

    We determined the expression of Kv2 channel subunits in rat somatosensory and motor cortex and tested for the contributions of Kv2 subunits to slowly inactivating K+ currents in supragranular pyramidal neurons. Single cell RT-PCR showed that virtually all pyramidal cells expressed Kv2.1 mRNA and ∼80% expressed Kv2.2 mRNA. Immunocytochemistry revealed striking differences in the distribution of Kv2.1 and Kv2.2 subunits. Kv2.1 subunits were clustered and located on somata and proximal dendrites of all pyramidal cells. Kv2.2 subunits were primarily distributed on large apical dendrites of a subset of pyramidal cells from deep layers. We used two methods for isolating currents through Kv2 channels after excluding contributions from Kv1 subunits: intracellular diffusion of Kv2.1 antibodies through the recording pipette and extracellular application of rStromatoxin-1 (ScTx). The Kv2.1 antibody specifically blocked the slowly inactivating K+ current by 25–50% (at 8 min), demonstrating that Kv2.1 subunits underlie much of this current in neocortical pyramidal neurons. ScTx (300 nm) also inhibited ∼40% of the slowly inactivating K+ current. We observed occlusion between the actions of Kv2.1 antibody and ScTx. In addition, Kv2.1 antibody- and ScTx-sensitive currents demonstrated similar recovery from inactivation and voltage dependence and kinetics of activation and inactivation. These data indicate that both agents targeted the same channels. Considering the localization of Kv2.1 and 2.2 subunits, currents from truncated dissociated cells are probably dominated by Kv2.1 subunits. Compared with Kv2.1 currents in expression systems, the Kv2.1 current in neocortical pyramidal cells activated and inactivated at relatively negative potentials and was very sensitive to holding potential. PMID:17379638

  5. Effects of caffeine on intracellular calcium, calcium current and calcium-dependent potassium current in anterior pituitary GH3 cells.

    PubMed

    Kramer, R H; Mokkapatti, R; Levitan, E S

    1994-01-01

    Caffeine elicits physiological responses in a variety of cell types by triggering the mobilization of Ca2+ from intracellular organelles. Here we investigate the effects of caffeine on intracellular Ca2+ concentration ([Ca2+]i) and ionic currents in anterior pituitary cells (GH3) cells. Caffeine has a biphasic effect on Ca(2+)-activated K+ current [IK(Ca)]: it induces a transient increase superimposed upon a sustained inhibition. While the transient increase coincides with a rise in [Ca2+]i, the sustained inhibition of IK(Ca) is correlated with a sustained inhibition of the L-type Ca2+ current. The L-type Ca2+ current is also inhibited by other agents that mobilize intracellular Ca2+, including thyrotropin releasing hormone (TRH) and ryanodine, but in a matter distinct from caffeine. Unlike the caffeine effect, the TRH-induced inhibition "washes-out" under whole-cell patch-clamp conditions and is eliminated by intracellular Ca2+ chelators. Likewise, the ryanodine-induced inhibition desensitizes while the caffeine-induced inhibition does not. Simultaneous [Ca2+]i and Ca2+ current measurements show that caffeine can inhibit Ca2+ current without changing [Ca2+]i. Single-channel recordings show that caffeine reduces mean open time without affecting single-channel conductance of L-type channels. Hence the effects of caffeine on ion channels in GH3 cells are attributable both to mobilization of intracellular Ca2+ and to a direct effect on the gating of L-type Ca2+ channels.

  6. Properties of voltage-gated potassium currents in nucleated patches from large layer 5 cortical pyramidal neurons of the rat

    PubMed Central

    Bekkers, John M

    2000-01-01

    Voltage-gated potassium currents were studied in nucleated outside-out patches obtained from large layer 5 pyramidal neurons in acute slices of sensorimotor cortex from 13- to 15-day-old Wistar rats (22–25 °C).Two main types of current were found, an A-current (IA) and a delayed rectifier current (IK), which were blocked by 4-aminopyridine (5 mm) and tetraethylammonium (30 mm), respectively.Recovery from inactivation was mono-exponential (for IA) or bi-exponential (for IK) and strongly voltage dependent. Both IA and IK could be almost fully inactivated by depolarising prepulses of sufficient duration. Steady-state inactivation curves were well fitted by the Boltzmann equation with half-maximal voltage (V½) and slope factor (k) values of −81.6 mV and −6.7 mV for IA, and −66.6 mV and −9.2 mV for IK. Peak activation curves were described by the Boltzmann equation with V½ and k values of −18.8 mV and 16.6 mV for IA, and −9.6 mV and 13.2 mV for IK.IA inactivated mono-exponentially during a depolarising test pulse, with a time constant (∼7 ms) that was weakly dependent on membrane potential. IK inactivated bi-exponentially with time constants (∼460 ms, ∼4.2 s) that were also weakly voltage dependent. The time to peak of both IA and IK depended strongly on membrane potential. The kinetics of IA and IK were described by a Hodgkin-Huxley-style equation of the form mNh, where N was 3 for IA and 1 for IK.These results provide a basis for understanding the role of voltage-gated potassium currents in the firing properties of large layer 5 pyramidal neurons of the rat neocortex. PMID:10856115

  7. Calcium-mediated decrease of a voltage-dependent potassium current.

    PubMed Central

    Alkon, D L; Shoukimas, J J; Heldman, E

    1982-01-01

    Elevated intracellular Ca++ concentration reduces the amplitude of an early, voltage-dependent K+ current (IA) in the Type B photoreceptor of Hermissenda crassicornis. Internal Ca++ is increased by activating a voltage and light-dependent Ca++ current present in these cells or by direct iontophoresis of Ca++ ions. Substitution of Ba++ for Ca++ or elimination of Ca++ from the sea water bathing the cells abolishes the reduction in IA during paired light and depolarizing voltage steps. The delayed K+ current (IB) in these cells is also reduced during paired light and voltage steps, but this decrease of IB is not affected by removal of extracellular Ca++. IB (but not IA), apparently much less dependent on intracellular Ca++ levels, is reduced by light alone. Ca++ iontophoresis also abolishes the light-dependent Na+ current, which recovers with a time course of minutes. PMID:7183338

  8. 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.

  9. Epac activator critically regulates action potential duration by decreasing potassium current in rat adult ventricle.

    PubMed

    Brette, Fabien; Blandin, Erick; Simard, Christophe; Guinamard, Romain; Sallé, Laurent

    2013-04-01

    Sympathetic stimulation is an important modulator of cardiac function via the classic cAMP-dependent signaling pathway, PKA. Recently, this paradigm has been challenged by the discovery of a family of guanine nucleotide exchange proteins directly activated by cAMP (Epac), acting in parallel to the classic signaling pathway. In cardiac myocytes, Epac activation is known to modulate Ca(2+) cycling yet their actions on cardiac ionic currents remain poorly characterized. This study attempts to address this paucity of information using the patch clamp technique to record action potential (AP) and ionic currents on rat ventricular myocytes. Epac was selectively activated by 8-CPT-AM (acetoxymethyl ester form of 8-CPT). AP amplitude, maximum depolarization rate and resting membrane amplitude were unaltered by 8-CPT-AM, strongly suggesting that Na(+) current and inward rectifier K(+) current are not regulated by Epac. In contrast, AP duration was significantly increased by 8-CPT-AM (prolongation of duration at 50% and 90% of repolarization by 41±10% and 43±8% respectively, n=11). L-type Ca(2+) current density was unaltered by 8-CPT-AM (n=16) so this cannot explain the action potential lengthening. However, the steady state component of K(+) current was significantly inhibited by 8-CPT-AM (-38±6%, n=15), while the transient outward K(+) current was unaffected by 8-CPT-AM. These effects were PKA-independent since they were observed in the presence of PKA inhibitor KT5720. Isoprenaline (100nM) induced a significant prolongation of AP duration, even in the presence of KT5720. This study provides the first evidence that the cAMP-binding protein Epac critically modulates cardiac AP duration by decreasing steady state K(+) current. These observations may be relevant to diseases in which Epac is upregulated, like cardiac hypertrophy.

  10. Characterization of the rapidly activating delayed rectifier potassium current, I (Kr), in HL-1 mouse atrial myocytes.

    PubMed

    Toyoda, Futoshi; Ding, Wei-Guang; Zankov, Dimitar P; Omatsu-Kanbe, Mariko; Isono, Takahiro; Horie, Minoru; Matsuura, Hiroshi

    2010-06-01

    HL-1 is the adult murine cardiac cell line that can be passaged repeatedly in vitro without losing differentiated phenotype. The present study was designed to characterize the rapidly activating delayed rectifier potassium current, I (Kr), endogenously expressed in HL-1 cells using the whole-cell patch-clamp technique. In the presence of nisoldipine, depolarizing voltage steps applied from a holding potential of -50 mV evoked the time-dependent outward current, followed by slowly decaying outward tail current upon return to the holding potential. The amplitude of the current increased with depolarizations up to 0 mV but then progressively decreased with further depolarizations. The time-dependent outward current as well as the tail current were highly sensitive to block by E-4031 and dofetilide (IC(50) of 21.1 and 15.1 nM, respectively) and almost totally abolished by micromolar concentrations of each drug, suggesting that most of the outward current in HL-1 cells was attributable to I (Kr). The magnitude of I (Kr) available from HL-1 cells (18.1 +/- 1.5 pA pF(-1)) was sufficient for reliable measurements of various gating parameters. RT-PCR and Western blot analysis revealed the expression of alternatively spliced forms of mouse ether-a-go-go-related genes (mERG1), the full-length mERG1a and the N-terminally truncated mERG1b isoforms. Knockdown of mERG1 transcripts with small interfering RNA (siRNA) dramatically reduced I (Kr) amplitude, confirming the molecular link of mERG1 and I (Kr) in HL-1 cells. These findings demonstrate that HL-1 cells possess I (Kr) with properties comparable to those in native cardiac I (Kr) and provide an experimental model suitable for studies of I (Kr) channels.

  11. 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

  12. Changes of extracellular potassium activity induced by electric current through brain tissue in the rat.

    PubMed Central

    Gardner-Medwin, A R; Nicholson, C

    1983-01-01

    Ion-selective micro-electrodes have been used to measure K+ and Ca2+ activity changes in extracellular space beneath the surface of the neocortex and cerebellar cortex during current flow across the tissue surface in anaesthetized rats. Inward currents produced decreases of [K+]o and outward currents produced increases, with insignificant changes in [Ca2+]o. Changes of [K+]o were largest just under the surface of the tissue, but were detectable down to depths of ca. 1 mm. With appropriate sitting of electrodes in the cerebellar cortex, currents of 22 microA mm-2 for 400 sec produced changes averaging -42% for inward current and +66% for outward current. The [K+]o changes near the surface were most rapid immediately after the onset of current and more gradual after some tens of seconds. Deeper within the tissue the rate of change was more uniform and after the end of stimulation the return to base line was slower. The amplitude, depth dependence and time course of the [K+]o changes were in reasonable agreement with the results calculated for a model in which K+ moves partly through extracellular space but primarily through membranes and cytoplasm within the tissue. The [K+]o changes were not attributable to variations in neuronal activity, although unit activity could be modified by current, since alternating currents failed to produce [K+]o changes and neither 0.1 mM-tetrodotoxin nor 5 mM-Mn2+ abolished the changes. The [K+]o changes were not abolished by topically applied ouabain (4 X 10(-4) M), 2,4-dinitrophenol (20 mM) or iodoacetate (10 mM), or by asphyxiation. Consequently the [K+]o changes are not dependent on metabolism. The data suggest that there is a selective mechanism for passive K+ transport in an electrochemical gradient within brain tissue that results in higher K+ fluxes than could be supported by ionic mobility in the extracellular fluid. This mechanism exists not only at the surface but within the brain parenchyma and may involve current flow

  13. Duration differences of corticostriatal responses in striatal projection neurons depend on calcium activated potassium currents

    PubMed Central

    Arias-García, Mario A.; Tapia, Dagoberto; Flores-Barrera, Edén; Pérez-Ortega, Jesús E.; Bargas, José; Galarraga, Elvira

    2013-01-01

    The firing of striatal projection neurons (SPNs) exhibits afterhyperpolarizing potentials (AHPs) that determine discharge frequency. They are in part generated by Ca2+-activated K+-currents involving BK and SK components. It has previously been shown that suprathreshold corticostriatal responses are more prolonged and evoke more action potentials in direct pathway SPNs (dSPNs) than in indirect pathway SPNs (iSPNs). In contrast, iSPNs generate dendritic autoregenerative responses. Using whole cell recordings in brain slices, we asked whether the participation of Ca2+-activated K+-currents plays a role in these responses. Secondly, we asked if these currents may explain some differences in synaptic integration between dSPNs and iSPNs. Neurons obtained from BAC D1 and D2 GFP mice were recorded. We used charybdotoxin and apamin to block BK and SK channels, respectively. Both antagonists increased the depolarization and delayed the repolarization of suprathreshold corticostriatal responses in both neuron classes. We also used NS 1619 and NS 309 (CyPPA), to enhance BK and SK channels, respectively. Current enhancers hyperpolarized and accelerated the repolarization of corticostriatal responses in both neuron classes. Nevertheless, these drugs made evident that the contribution of Ca2+-activated K+-currents was different in dSPNs as compared to iSPNs: in dSPNs their activation was slower as though calcium took a diffusion delay to activate them. In contrast, their activation was fast and then sustained in iSPNs as though calcium flux activates them at the moment of entry. The blockade of Ca2+-activated K+-currents made iSPNs to look as dSPNs. Conversely, their enhancement made dSPNs to look as iSPNs. It is concluded that Ca2+-activated K+-currents are a main intrinsic determinant causing the differences in synaptic integration between corticostriatal polysynaptic responses between dSPNs and iSPNs. PMID:24109439

  14. Activity-dependent modulation of the presynaptic potassium current in the frog neuromuscular junction.

    PubMed Central

    Miralles, F; Solsona, C

    1996-01-01

    1. Changes in the electrical properties of frog motor nerve endings caused by the invasion of an action potential were studied by the perineural recording technique. Two equal supramaximal stimuli separated by a variable time interval were applied to the nerve trunk. The latency and amplitude of the deflections associated with the nodal Na+ current and presynaptic K+ current elicited by the second pulse were compared with control currents. 2. The deflection associated with the presynaptic K+ current elicited in response to the second stimulus was absent at the shortest interstimulus interval and showed a progressive increase in its amplitude as the interstimulus interval was lengthened, reaching values greater than control in most terminals. During the same period the nodal Na+ current did not change. 3. The experimental results were compared with a computer model of the distal axonal segment and its terminal. Response of the model to twin-pulse stimulation was in marked disagreement with the experimental results unless an inactivating K+ channel, with properties derived ad hoc, was incorporated into the simulation. 4. These results suggest that in the first 6-7 ms after a nerve impulse has invaded a frog motor nerve ending, maximal K+ conductance remains below the value at rest due to the fast inactivation of a K+ conductance. Following this, there is a period in which K+ conductance is greater than control values although the basis for this is unknown. PMID:8887778

  15. Somatostatinergic modulation of firing pattern and calcium-activated potassium currents in medium spiny neostriatal neurons.

    PubMed

    Galarraga, E; Vilchis, C; Tkatch, T; Salgado, H; Tecuapetla, F; Perez-Rosello, T; Perez-Garci, E; Hernandez-Echeagaray, E; Surmeier, D J; Bargas, J

    2007-05-11

    Somatostatin is synthesized and released by aspiny GABAergic interneurons of the neostriatum, some of them identified as low threshold spike generating neurons (LTS-interneurons). These neurons make synaptic contacts with spiny neostriatal projection neurons. However, very few somatostatin actions on projection neurons have been described. The present work reports that somatostatin modulates the Ca(2+) activated K(+) currents (K(Ca) currents) expressed by projection cells. These actions contribute in designing the firing pattern of the spiny projection neuron; which is the output of the neostriatum. Small conductance (SK) and large conductance (BK) K(Ca) currents represent between 30% and 50% of the sustained outward current in spiny cells. Somatostatin reduces SK-type K(+) currents and at the same time enhances BK-type K(+) currents. This dual effect enhances the fast component of the after hyperpolarizing potential while reducing the slow component. Somatostatin then modifies the firing pattern of spiny neurons which changed from a tonic regular pattern to an interrupted "stuttering"-like pattern. Semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) tissue expression analysis of dorsal striatal somatostatinergic receptors (SSTR) mRNA revealed that all five SSTR mRNAs are present. However, single cell RT-PCR profiling suggests that the most probable receptor in charge of this modulation is the SSTR2 receptor. Interestingly, aspiny interneurons may exhibit a "stuttering"-like firing pattern. Therefore, somatostatin actions appear to be the entrainment of projection neurons to the rhythms generated by some interneurons. Somatostatin is then capable of modifying the processing and output of the neostriatum.

  16. Adenosine-activated potassium current in smooth muscle cells isolated from the pig coronary artery.

    PubMed Central

    Dart, C; Standen, N B

    1993-01-01

    1. The perforated patch technique with nystatin or amphotericin was used to record whole cell currents activated by adenosine in smooth muscle cells isolated enzymatically from pig coronary arteries. 2. Adenosine (5-40 microM) activated an outward current at a holding potential of 0 mV in 5 mM [K+]o and an inward current at -60 mV in 143 mM [K+]o. The dependence of the reversal potential for the adenosine-activated current on [K+]o suggests that it flows through K+ channels, while its current-voltage relation is consistent with the channels showing little voltage dependence. 3. The adenosine-activated current was inhibited by the sulphonylurea glibenclamide (5 microM) and by phencyclidine (5 microM). It was unaffected by charybdotoxin (50 nM) or apamin (100 nM), blockers of large and small conductance Ca(2+)-activated K+ channels respectively. 4. At -60 mV in 143 mM K+ solution, openings of single channels passing a current of just over -2 pA could sometimes be detected in the absence of adenosine. Openings became more frequent after the application of adenosine, with several levels then being detected. Openings of channels with a larger conductance were sometimes also seen in the presence of adenosine. Fluctuation analysis gave somewhat lower estimates of unitary current than did direct measurements. 5. The effect of adenosine could be mimicked by the A1 receptor agonist CCPA (2-chloro-N6-cyclopentyladenosine), while the A2 agonist CGS 21680 (2-p-(2-carboxethyl)phenethylamino-5'-N-ethylcarboxamido adenosine hydrochloride) was without effect. The response to adenosine was inhibited by the A1 antagonist DPCPX (8-cyclopentyl-1,3-dipropylxanthine), but was unaffected by the A2 antagonist CGS 15943A (5-amino-9-chloro-2-(2-furanyl)-1,2,4- triazolo[1,5-C]quinazoline monomethanesulphonate). 6. Our results suggest that adenosine acts at an A1 receptor to activate K+ channels. We consider it most likely that these are ATP-dependent K+ channels. We discuss the mechanism by

  17. Some effects of n-pentane on the sodium and potassium currents of the squid giant axon.

    PubMed Central

    Haydon, D A; Kimura, J E

    1981-01-01

    1. Sodium and potassium currents have been recorded in intracellularly perfused squid giant axons before, during and after exposure to solutions of n-pentane in artificial sea water. 2. The currents were fitted with equations similar to those proposed by Hodgkin & Huxley (1952) and the changes in the parameters of these equations in the presence of pentane were calculated. 3. In the range of membrane potential -40 to 40 mV, the time constants for activation (tau m) and inactivation (tau h) of the Na current, and for activation (tau n) of the K current were all reduced by the pentane. 4. The curve of the steady-state inactivation parameter (h infinity) for the Na current against membrane potential was shifted by the pentane in a hyperpolarizing direction (at h infinity = 0.5 this shift was approx. -15 mV in 275 microM-pentane) and the slope at all potentials was reduced. 5. The curve of the steady-state activation parameter (m infinity) for the Na current against membrane potential was also shifted by the pentane in a hyperpolarizing direction (in 153 microM-pentane, 10 mV at m infinity = 0.5). 6. The maximum Na and K conductances gNa and gK were lowered by the pentane, though not usually completely reversibly. 7. The changes in position and slope of the steady-state inactivation curve have been tentatively accounted for in terms of an increase in membrane thickness. PMID:6267268

  18. Potassium Counts.

    ERIC Educational Resources Information Center

    Gipps, John

    1995-01-01

    Presents an activity to determine whether the radioactivity of a pure potassium salt is directly proportional to the amount of potassium in it and whether this could be used as a method of analysis for potassium in a solid. (MKR)

  19. Potassium Counts.

    ERIC Educational Resources Information Center

    Gipps, John

    1995-01-01

    Presents an activity to determine whether the radioactivity of a pure potassium salt is directly proportional to the amount of potassium in it and whether this could be used as a method of analysis for potassium in a solid. (MKR)

  20. Update on the slow delayed rectifier potassium current (I(Ks)): role in modulating cardiac function.

    PubMed

    Liu, Zhenzhen; Du, Lupei; Li, Minyong

    2012-01-01

    The slow delayed rectifier current (I(Ks)) is the slow component of cardiac delayed rectifier current and is critical for the late phase repolarization of cardiac action potential. This current is also an important target for Sympathetic Nervous System (SNS) to regulate the cardiac electivity to accommodate to heart rate alterations in response to exercise or emotional stress and can be up-regulated by β- adrenergic or other signal molecules. I(Ks) channel is originated by the co-assembly of pore-forming KCNQ1 α-subunit and accessory KCNE1 β-subunit. Mutations in any subunit can bring about severe long QT syndrome (LQT-1, LQT-5) as characterized by deliquium, seizures and sudden death. This review summarizes the normal physiological functions and molecular basis of I(Ks) channels, as well as illustrates up-to-date development on its blockers and activators. Therefore, the current extensive survey should generate fundamental understanding of the role of I(Ks) channel in modulating cardiac function and donate some instructions to the progression of I(Ks) blockers and activators as potential antiarrhythmic agents or pharmacological tools to determine the physiological and pathological function of I(Ks).

  1. alpha2-Adrenoceptor-mediated potassium currents in acutely dissociated rat locus coeruleus neurones.

    PubMed

    Arima, J; Kubo, C; Ishibashi, H; Akaike, N

    1998-04-01

    1. The noradrenaline (NA)-activated response was investigated in neurones acutely dissociated from the rat locus coeruleus (LC) using nystatin-perforated, conventional whole-cell and inside-out patch recording modes under current- and voltage-clamp conditions. 2. Under current-clamp conditions, NA hyperpolarized the LC neurones, abolishing the spontaneous action potentials. In voltage-clamp studies, NA induced an inwardly rectifying K+ current (INA) in a concentration-dependent manner with a half-maximum effective concentration of 2.2 x 10(-7) M. 3. INA was mimicked by the alpha2-agonist UK14304 but was inhibited by either the alpha2B/alpha2C antagonist ARC239 or the alpha1- and alpha2B/alpha2C antagonist prazosin, suggesting the contribution of alpha2B/alpha2C adrenoceptors. 4. INA was inhibited by the intracellular application of GDPbetaS but fully activated by intracellular perfusion of GTPgammaS. 5. In the inside-out recording mode, the application of GTP to the cytoplasmic side of the patch membrane markedly enhanced the open probability of the NA-activated single channels which represented the inwardly rectifying properties. 6. These results indicate that the activation of alpha2B/alpha2C adrenoceptors coupled with GTP-binding protein directly activates the inwardly rectifying K+ currents in rat LC neurones, thus resulting in a decrease in the spontaneous firing activities.

  2. α2-Adrenoceptor-mediated potassium currents in acutely dissociated rat locus coeruleus neurones

    PubMed Central

    Arima, Junichi; Kubo, Chiharu; Ishibashi, Hitoshi; Akaike, Norio

    1998-01-01

    The noradrenaline (NA)-activated response was investigated in neurones acutely dissociated from the rat locus coeruleus (LC) using nystatin-perforated, conventional whole-cell and inside-out patch recording modes under current- and voltage-clamp conditions. Under current-clamp conditions, NA hyperpolarized the LC neurones, abolishing the spontaneous action potentials. In voltage-clamp studies, NA induced an inwardly rectifying K+ current (INA) in a concentration-dependent manner with a half-maximum effective concentration of 2.2 × 10−7 m. INA was mimicked by the α2-agonist UK14304 but was inhibited by either the α2B/α2C antagonist ARC239 or the α1- and α2B/α2C antagonist prazosin, suggesting the contribution of α2B/α2C adrenoceptors. INA was inhibited by the intracellular application of GDPβS but fully activated by intracellular perfusion of GTPγS. In the inside-out recording mode, the application of GTP to the cytoplasmic side of the patch membrane markedly enhanced the open probability of the NA-activated single channels which represented the inwardly rectifying properties. These results indicate that the activation of α2B/α2C adrenoceptors coupled with GTP-binding protein directly activates the inwardly rectifying K+ currents in rat LC neurones, thus resulting in a decrease in the spontaneous firing activities. PMID:9490817

  3. Sodium--potassium pump current in rabbit sino-atrial node cells.

    PubMed Central

    Sakai, R; Hagiwara, N; Matsuda, N; Kassanuki, H; Hosoda, S

    1996-01-01

    1. The Na(+)-K+ pump current (Ip) was studied in sino-atrial (SA) node cells of rabbits using the whole-cell patch-clamp technique. 2. With 50 mM Na+ in the pipette solution ([Na+]pip), changing the external K+ concentration (-K+-o) from 0 to 5.4 mM caused the holding current to shift in an outward direction and reach a new steady state. The current-voltage relationships obtained by subtraction of current traces recorded at 0 mM Ko+ from those recorded at 5.4 mM Ko+ revealed time-independent and voltage-dependent characteristics. The external K(+)-induced current was completely blocked by external application of 10 microM ouabain, indicating the existence of Ip in SA node cells of rabbit heart. 3. Ip increased as [K+]o increased. With 30 mM Na+pip, Ip at 0 mV was activated by [K+]o with non-linear least-squares fit parameters for the Hill equation of K0.5 of 1.4 mM and a Hill coefficient (nH) of 1.2 (n = 7). 4. The cation dependence of the K+ site of the Na(+)-K+ pump was examined using various monovalent cations. The sequence was K+ > or = Rb+ > Cs+ > > > Li+. 5. Ip at 0 mV also increased as [Na+]pip was increased from 10 to 150 mM at 5.4 mM Ko+, with a K0.5 value of 14 mM and a nH of 1.3 (n = 54). 6. Ip at 0 mV was reduced by lowering the temperature from 37 to 25 degrees C with 30 mM Na+pip and 5.4 mM Ko+. The temperature coefficient (Q10) for Ip was 2.1 (n = 27). 7. With 10 mM Na+pip and 5.4 mM Ko+, the half-activation voltage of Ip was -52 +/- 16 mV and the current at this voltage was 22.5 +/- 3.5 pA (n = 10), indicating that Ip contributes significantly to the background outward current during the normal pacemaker potential of SA node cells. PMID:8745278

  4. Voltage-dependent activation of potassium current in Helix neurones by endogenous cellular calcium.

    PubMed Central

    Akaike, N; Brown, A M; Dahl, G; Higashi, H; Isenberg, G; Tsuda, Y; Yatani, A

    1983-01-01

    1. The effect of endogenous Ca on potential-dependent K current IKD, was examined in identifiable neurones of Helix aspersa. The suction pipette method of internal perfusion was used along with a combined voltage-clamp method in which the membrane potential was measured by a separate glass micro-electrode and the current was passed by the suction pipette. Activation of the potential-dependent A current, IA, was prevented by using holding potentials of -40 mV where IA is inactivated and by the addition of the A-current blocker 4-aminopyridine. Activation of K currents by transmembrane Ca current, IKCa, was suppressed by Co substitution for Ca ion extracellularly. 2. Under these conditions, IKD rose to a peak value and then subsided to a steady level. The current-voltage (I-V) relationship for peak IKD had an upward bump at about +50 mV that gave it an S-shape. The I-V curve for steady IKD rose continuously. Peak and steady IKD were reduced by perfusing with EGTA or F ions intracellularly. The EGTA effect occurred at intracellular Ca activity levels below 10(-7) M. Increases in the concentration of EGTAi at constant Cai had no additional effect; however, recovery experiments do not allow us to rule out some direct action of EGTA on IKD. 3. Prolonged extracellular perfusion with Co-substituted solutions also reduced IKD and the effects occurred more quickly when the solutions were made hypertonic or caffeine was added to them. The peak transient was abolished, and the small remaining steady IKD (about 5-10% of normal peak IKD) was blocked by tetraethylammonium. IKD could be restored by the temporary reintroduction of Ca in the extracellular solution. 4. The S-shape of the peak I-V relationship for IKD may be due to Ca released from an endogenous site by membrane depolarization. The reduction of steady and peak IKD to very low values by Ca chelators or prolonged perfusion with Ca-free solutions indicates that Cai is important for activation of these K channels. 5

  5. Transient calcium-dependent potassium current in magnocellular neurosecretory cells of the rat supraoptic nucleus.

    PubMed

    Bourque, C W

    1988-03-01

    1. Magnocellular neurosecretory neurones were impaled in the supraoptic nucleus of perfused explants of rat hypothalamus. Membrane currents were studied at 35 degrees C using the single-microelectrode voltage-clamp technique. 2. Depolarizing voltage steps applied from -100 mV evoked a transient outward current (TOC) from a threshold of -75 mV. From this potential, the amplitude of the current increased non-linearly with voltage. 3. Following its activation TOC reached a peak within 7 ms and subsequently decayed monotonically with a time constant of 30 ms. This time constant did not vary significantly with voltage between -75 and -55 mV. 4. The TOC showed complete steady-state inactivation at potentials positive to -55 mV. Inactivation was removed by hyperpolarization, with a mid-point near -80 mV. The removal of inactivation followed a complex time course with distinct fast (tens of milliseconds) and slow (hundreds of milliseconds) components. 5. Tail current measurements revealed that the TOC equilibrium potential (ETOC) lies near -97 mV in the presence of 3 mM [K+]o. Increasing [K+]o caused a decrease of TOC amplitude and a shift in ETOC of 57 mV/log [K+]o. The TOC is therefore predominantly a K+ current. 6. The TOC was unaffected by tetraethylammonium (up to 12 mM) but was reversibly reduced by 4-aminopyridine (ca. 50% block at 1.0 mM) and dendrotoxin (ca. 50% block at 4 nM). 7. The TOC was strongly inhibited (greater than 70%) by adding Co2+ or Mn2+ (1-3 mM) or Cd2+ (50-400 microM) to Ca-containing solutions, or by removal of Ca2+ from the perfusate. These effects were not accompanied by detectable changes in threshold voltage. The amplitude of TOC was also depressed by the organic Ca2+ channel blocker methoxyverapamil (D600). Finally replacement of Ca2+ by Ba2+ in the perfusate completely and reversibly abolished the TOC. 8. These findings suggest that neurosecretory neurones of the rat supraoptic nucleus display a transient K+ current which is strongly

  6. Transient calcium-dependent potassium current in magnocellular neurosecretory cells of the rat supraoptic nucleus.

    PubMed Central

    Bourque, C W

    1988-01-01

    1. Magnocellular neurosecretory neurones were impaled in the supraoptic nucleus of perfused explants of rat hypothalamus. Membrane currents were studied at 35 degrees C using the single-microelectrode voltage-clamp technique. 2. Depolarizing voltage steps applied from -100 mV evoked a transient outward current (TOC) from a threshold of -75 mV. From this potential, the amplitude of the current increased non-linearly with voltage. 3. Following its activation TOC reached a peak within 7 ms and subsequently decayed monotonically with a time constant of 30 ms. This time constant did not vary significantly with voltage between -75 and -55 mV. 4. The TOC showed complete steady-state inactivation at potentials positive to -55 mV. Inactivation was removed by hyperpolarization, with a mid-point near -80 mV. The removal of inactivation followed a complex time course with distinct fast (tens of milliseconds) and slow (hundreds of milliseconds) components. 5. Tail current measurements revealed that the TOC equilibrium potential (ETOC) lies near -97 mV in the presence of 3 mM [K+]o. Increasing [K+]o caused a decrease of TOC amplitude and a shift in ETOC of 57 mV/log [K+]o. The TOC is therefore predominantly a K+ current. 6. The TOC was unaffected by tetraethylammonium (up to 12 mM) but was reversibly reduced by 4-aminopyridine (ca. 50% block at 1.0 mM) and dendrotoxin (ca. 50% block at 4 nM). 7. The TOC was strongly inhibited (greater than 70%) by adding Co2+ or Mn2+ (1-3 mM) or Cd2+ (50-400 microM) to Ca-containing solutions, or by removal of Ca2+ from the perfusate. These effects were not accompanied by detectable changes in threshold voltage. The amplitude of TOC was also depressed by the organic Ca2+ channel blocker methoxyverapamil (D600). Finally replacement of Ca2+ by Ba2+ in the perfusate completely and reversibly abolished the TOC. 8. These findings suggest that neurosecretory neurones of the rat supraoptic nucleus display a transient K+ current which is strongly

  7. Androgens block outward potassium currents and decrease spontaneous action potentials in GH3 cells.

    PubMed

    Suárez, Lorena; Bilal, Usama; Bordallo, Javier; Cantabrana, Begoña; Sánchez, Manuel

    2015-01-01

    Androgens produce nongenomic effects in several cells by different mechanisms, including ion channel modulation. Adenohypophyseal cells express several K(+) channels, including voltage and Ca(2+)-dependent K(+) (BK) channels, which might be the target of androgens to modulate cellular action potentials and hormonal secretion. Androgen effects were studied in GH3 cells (from anterior pituitary rat tumor) by means of the patch-clamp technique. Cells were continuously perfused with saline solution, in the absence or presence of the androgens studied, while applying 40 mV pulses of 400 ms from a holding potential of -60 mV in whole-cell configuration with nystatin-perforated patches. Androgens reversibly blocked noninactivating K(+) currents in a concentration-dependent manner without a latency period and with an order of efficacy of: 5β-dihydrotestosterone (DHT)>testosterone>5α-DHT. RT-PCR showed two isoforms of the α-pore forming subunits of BK channels. These channels are responsible for one third of the noninactivating current, according to the blockade of paxilline, a selective BK antagonist. Androgens seem to directly interact with BK channels since they were blocked in excised inside-out patches and independent of the whole-cell configuration and the NO-cGMP-dependent pathway. Testosterone, but not 5α- or 5β-DHT, increased BK currents in HEK-293 cells overexpressing the short isoform, suggesting a cellular selectivity based on the α-subunits. The effect on noninactivating currents may be responsible for the decrease of spontaneous action potential frequency. Long-term cellular incubation with testosterone did not modify noninactivating currents density in GH3 cells. It is remarkable that 5β-DHT, a reductase metabolite with weak androgenic activity, was the most efficient blocker.

  8. Molecular basis of voltage-dependent potassium currents in porcine granulosa cells.

    PubMed

    Mason, Diane E; Mitchell, Kathy E; Li, Yan; Finley, Melissa R; Freeman, Lisa C

    2002-01-01

    The major objective of this study was to elucidate the molecular bases for K(+) current diversity in porcine granulosa cells (GC). Two delayed rectifier K(+) currents with distinct electrophysiological and pharmacological properties were recorded from porcine GC by using whole-cell patch clamp: 1) a slowly activating, noninactivating current (I(Ks)) antagonized by clofilium, 293B, L-735,821, and L-768,673; and 2) an ultrarapidly activating, slowly inactivating current (I(Kur)) antagonized completely by clofilium and 4-aminopyridine and partially by tetraethylammonium, charybdotoxin, dendrotoxin, and kaliotoxin. The molecular identity of the K(+) channel genes underlying I(Ks) and I(Kur) was examined using reverse transcription-polymerase chain reaction and immunoblotting to detect K(+) channel transcripts and proteins. We found that GC could express multiple voltage-dependent K(+) (Kv) channel subunits, including KCNQ1, KCNE1, Kv1.1, Kv1.2, Kv1.3, Kv1.4, Kv1.5, Kv1.6, Kvbeta1.3, and Kvbeta2. Coimmunoprecipitation was used to establish the hetero-oligomeric nature of granulosa cell Kv channels. KCNE1 and KCNQ1 were coassociated in GC, and their expression coincided with the expression of I(Ks). Extensive coassociation of the various Kv alpha- and beta-subunits was also documented, suggesting that the diverse electrophysiological and pharmacological properties of I(Kur) currents may reflect variation in the composition and stoichiometry of the channel assemblies, as well as differences in post-translational modification of contributing Kv channel subunits. Our findings provide an essential background for experimental definition of granulosa K(+) channel function(s). It will be critical to define the functional roles of specific GC K(+) channels, because these proteins may represent either novel targets for assisted reproduction or potential sites of drug toxicity.

  9. Potassium Secondary Batteries.

    PubMed

    Eftekhari, Ali; Jian, Zelang; Ji, Xiulei

    2017-02-08

    Potassium may exhibit advantages over lithium or sodium as a charge carrier in rechargeable batteries. Analogues of Prussian blue can provide millions of cyclic voltammetric cycles in aqueous electrolyte. Potassium intercalation chemistry has recently been demonstrated compatible with both graphite and nongraphitic carbons. In addition to potassium-ion batteries, potassium-O2 (or -air) and potassium-sulfur batteries are emerging. Additionally, aqueous potassium-ion batteries also exhibit high reversibility and long cycling life. Because of potentially low cost, availability of basic materials, and intriguing electrochemical behaviors, this new class of secondary batteries is attracting much attention. This mini-review summarizes the current status, opportunities, and future challenges of potassium secondary batteries.

  10. Structural basis for the decrease in the outward potassium channel current induced by lanthanum.

    PubMed

    Wang, Li Hong; Jiang, Na; Zhao, Bo; Li, Xiao Dong; Lu, Tian Hong; Ding, Xiao Lan; Huang, Xiao Hua

    2010-09-01

    The current of the outward K+ channel in the cell of horseradish treated with La3+ and the direct interaction between La3+ and the K+ channel protein were investigated using the whole-cell patch-clamp technique, molecular dynamics simulation, and quantum chemistry calculation methods. It was found for the first time that La3+ decreases the current of the K+ channel in the horseradish mesophyll cell. The decrease results from the formation of a coordination bond and hydrogen bond between La3+ and the K+ channel protein in the plasma membrane. The direct interaction destroys the native structure of the K+ channel protein, disturbing the function of the K+ channel protein in the cells. The results can provide the theoretical foundation for understanding the interaction between metal ions (especially high-valence metal ions) and the channel protein in organisms, including animal and plant cells.

  11. Rapidly inactivating and non-inactivating calcium-activated potassium currents in frog saccular hair cells

    PubMed Central

    Armstrong, Cecilia E; Roberts, William M

    2001-01-01

    Using a semi-intact epithelial preparation we examined the Ca2+-activated K+ (KCa) currents of frog (Rana pipiens) saccular hair cells. After blocking voltage-dependent K+ (KV) currents with 4-aminopyridine (4-AP) an outward current containing inactivating (Itransient) and non-inactivating (Isteady) components remained.The contribution of each varied greatly from cell to cell, with Itransient contributing from 14 to 90 % of the total outward current. Inactivation of Itransient was rapid (τ≈ 2–3 ms) and occurred within the physiological range of membrane potentials (V1/2=−63 mV). Recovery from inactivation was also rapid (τ≈ 10 ms).Suppression of both Itransient and Isteady by depolarizations that approached the Ca2+ equilibrium potential and by treatments that blocked Ca2+ influx (application Ca2+-free saline or Cd2+), suggest both are Ca2+ dependent. Both were blocked by iberiotoxin, a specific blocker of large-conductance KCa channels (BK), but not by apamin, a specific blocker of small-conductance KCa channels.Ensemble-variance analysis showed that Itransient and Isteady flow through two distinct populations of channels, both of which have a large single-channel conductance (∼100 pS in non-symmetrical conditions). Together, these data indicate that both Itransient and Isteady are carried through BK channels, one of which undergoes rapid inactivation while the other does not.Inactivation of Itransient could be removed by extracellular papain and could later be restored by intracellular application of the ‘ball’ domain of the auxiliary subunit (β2) thought to mediate BK channel inactivation in rat chromaffin cells. We hypothesize that Itransient results from the association of a similar β subunit with some of the BK channels and that papain removes inactivation by cleaving extracellular sites required for this association. PMID:11579156

  12. Potassium and sodium ion current noise in the membrane of the squid giant axon.

    PubMed Central

    Conti, F; De Felice, L J; Wanke, E

    1975-01-01

    1. The spectral density of current noise power from 20 mm segments of giant axons of the squid Loligo vulgaris has been measured under space-clamp and voltage-clamp conditions. From 4 to 1000 Hz the measured noise is larger by several orders of magnitude than the theoretical thermal noise. The amplifier's noise, which may yield appreciable contributions above 200 Hz, could be evaluated and subtracted from the total noise using direct measurements of the membrane impedance... PMID:1151828

  13. Inhibition of cardiac Kv1.5 potassium current by the anesthetic midazolam: mode of action

    PubMed Central

    Vonderlin, Nadine; Fischer, Fathima; Zitron, Edgar; Seyler, Claudia; Scherer, Daniel; Thomas, Dierk; Katus, Hugo A; Scholz, Eberhard P

    2014-01-01

    Midazolam is a short-acting benzodiazepine that is widely used in anesthesia. Despite its widespread clinical use, detailed information about cardiac side effects of midazolam is largely lacking. Using the double-electrode voltage clamp technique, we studied pharmacological effects of midazolam on heterologously expressed Kv1.5 channels underlying atrial repolarizing current IKur. Midazolam dose-dependently inhibited Kv1.5 current, yielding an IC50 of 17 μM in an HEK cell line and an IC50 of 104 μM in Xenopus oocytes. We further showed that midazolam did not affect the half-maximal activation voltage of Kv1.5 channels. However, a small negative shift of the inactivation curve could be observed. Midazolam acted as a typical open-channel inhibitor with rapid onset of block and without frequency dependence of block. Taken together, midazolam is an open channel inhibitor of cardiac Kv1.5 channels. These data add to the current understanding of the pharmacological profile of midazolam. PMID:25422586

  14. In vitro Arabidopsis pollen germination and characterization of the inward potassium currents in Arabidopsis pollen grain protoplasts.

    PubMed

    Fan, L M; Wang, Y F; Wang, H; Wu, W H

    2001-08-01

    The focus of this study is to investigate the regulatory role of K(+) influx in Arabidopsis pollen germination and pollen tube growth. Using agar-containing media, in vitro methods for Arabidopsis pollen germination have been successfully established for the first time. The pollen germination percentage was nearly 75% and the average pollen tube length reached 135 microm after a 6 h incubation. A decrease in external K(+) concentration from 1 mM to 35 microM resulted in 30% inhibition of pollen germination and 40% inhibition of pollen tube growth. An increase in external K(+) concentration from 1 mM to 30 mM stimulated pollen tube growth but inhibited pollen germination. To study how K(+) influx is associated with pollen germination and tube growth, regulation of the inward K(+) channels in the pollen plasma membrane was investigated by conducting patch-clamp whole-cell recording with pollen protoplasts. K(+) currents were first identified in Arabidopsis pollen protoplasts. The inward K(+) currents were insensitive to changes in cytoplasmic Ca(2+) but were inhibited by a high concentration of external Ca(2+). A decrease of external Ca(2+) concentration from 10 mM (control) to 1 mM had no significant effect on the inward K(+) currents, while an increase of external Ca(2+) concentration from 10 mM to 50 mM inhibited the inward K(+) currents by 46%. Changes in external pH significantly affected the magnitude, conductance, voltage-independent maximal conductance, and activation kinetics of the inward K(+) currents. The physiological importance of potassium influx mediated by the inward K(+)-channels during Arabidopsis pollen germination and tube growth is discussed.

  15. H-89 inhibits transient outward and inward rectifier potassium currents in isolated rat ventricular myocytes

    PubMed Central

    Pearman, Charles; Kent, William; Bracken, Nicolas; Hussain, Munir

    2006-01-01

    Voltage clamp was used to investigate the effects of N-[2-p-bromo-cinnamylamino)ethyl]-5-isoquinolinesulfonamide (H-89), a potent inhibitor of PKA, on transient outward K+ current (Ito) and inward rectifying K+ current (IK1) in rat cardiac muscle. Initial experiments, performed using descending voltage ramps, showed that H-89 inhibited both the outward and inward ramp currents in a concentration-dependent manner at concentrations between 5 and 60 μmol l−1. A similar degree of inhibition was observed when Ito and IK1 were recorded using square wave depolarising and hyperpolarising voltage steps, respectively. The IC50 was 35.8 μmol l−1 for Ito and 27.8 μmol l−1 for IK1 compared to 5.4 μmol l−1 for L-type Ca2+ current (ICa). The Hill coefficients for Ito, IK1 and ICa were −1.97, −1.60 and −1.21, respectively. In addition to inhibiting Ito amplitude, H-89 also accelerated the time to peak and the rate of voltage-dependent inactivation so that the time course of Ito was abbreviated. Paired-pulse protocols were performed to study the effects of H-89 on steady-state activation and inactivation as well as recovery from voltage-dependent inactivation. H-89 produced a concentration-dependent rightward shift in voltage-dependent activation but had no significant effect on steady-state inactivation. Recovery from voltage-dependent inactivation was delayed, although this was only visible at the highest concentration (60 μmol l−1) used. In experiments investigating the effects of elevated cyclic AMP, the β-adrenergic agonist isoprenaline and the phosphatase inhibitor calyculin A had no major effects on Ito or IK1. Data suggest that the effects of H-89 on K+ currents are more complex than simple inhibition of PKA-mediated phosphorylation. PMID:16799649

  16. The transient outward current in mice lacking the potassium channel gene Kv1.4

    PubMed Central

    London, Barry; Wang, Dao W; Hill, Joseph A; Bennett, Paul B

    1998-01-01

    The transient outward current (Ito) plays a prominent role in the repolarization phase of the cardiac action potential. Several K+ channel genes, including Kv1.4, are expressed in the heart, produce rapidly inactivating currents when heterologously expressed, and may be the molecular basis of Ito.We engineered mice homozygous for a targeted disruption of the K+ channel gene Kv1.4 and compared Ito in wild-type (Kv1.4+/+), heterozygous (Kv1.4+/-) and homozygous ‘knockout’ (Kv1.4−/−) mice. Kv1.4 RNA was truncated in Kv1.4−/− mice and protein expression was absent.Adult myocytes isolated from Kv1.4+/+, Kv1.4+/− and Kv1.4−/− mice had large rapidly inactivating outward currents. The peak current densities at 60 mV (normalized by cellular capacitance, in pA pF−1; means ± s.e.m.) were 53.8 ± 5.3, 45.3 ± 2.2 and 44.4 ± 2.8 in cells from Kv1.4+/+, Kv1.4+/− and Kv1.4−/− mice, respectively (P < 0.02 for Kv1.4+/+ vs. Kv1.4−/−). The steady-state values (800 ms after the voltage clamp step) were 30.9 ± 2.9, 26.9 ± 3.8 and 23.5 ± 2.2, respectively (P < 0.02 for Kv1.4+/+ vs. Kv1.4−/−). The inactivating portion of the current was unchanged in the targeted mice.The voltage dependence and time course of inactivation were not changed by targeted disruption of Kv1.4. The mean best-fitting V½ (membrane potential at 50 % inactivation) values for myocytes from Kv1.4 +/+, Kv1.4+/− and Kv1.4−/− mice were -53.5 ± 3.7, -51.1 ± 2.6 and -54.2 ± 2.4 mV, respectively. The slope factors (k) were -10.1 ± 1.4, -8.8 ± 1.4 and -9.5 ± 1.2 mV, respectively. The fast time constants for development of inactivation at -30 mV were 27.8 ± 2.2, 26.2 ± 5.1 and 19.6 ± 2.1 ms in Kv1.4+/+, Kv1.4+/− and Kv1.4−/− myocytes, respectively. At +30 mV, they were 35.5 ± 2.6, 30.0 ± 2.1 and 28.7 ± 1.6 ms, respectively. The time constants for the rapid phase of recovery from inactivation at -80 mV were 32.5 ± 8.2, 23.3 ± 1.8 and 39.0 ± 3.7 ms, respectively

  17. Photoperiod Modulates Fast Delayed Rectifier Potassium Currents in the Mammalian Circadian Clock

    PubMed Central

    Meijer, Johanna H.; Michel, Stephan

    2016-01-01

    One feature of the mammalian circadian clock, situated in the suprachiasmatic nucleus (SCN), is its ability to measure day length and thereby contribute to the seasonal adaptation of physiology and behavior. The timing signal from the SCN, namely the 24 hr pattern of electrical activity, is adjusted according to the photoperiod being broader in long days and narrower in short days. Vasoactive intestinal peptide and gamma-aminobutyric acid play a crucial role in intercellular communication within the SCN and contribute to the seasonal changes in phase distribution. However, little is known about the underlying ionic mechanisms of synchronization. The present study was aimed to identify cellular mechanisms involved in seasonal encoding by the SCN. Mice were adapted to long-day (light–dark 16:8) and short-day (light–dark 8:16) photoperiods and membrane properties as well as K+ currents activity of SCN neurons were measured using patch-clamp recordings in acute slices. Remarkably, we found evidence for a photoperiodic effect on the fast delayed rectifier K+ current, that is, the circadian modulation of this ion channel’s activation reversed in long days resulting in 50% higher peak values during the night compared with the unaltered day values. Consistent with fast delayed rectifier enhancement, duration of action potentials during the night was shortened and afterhyperpolarization potentials increased in amplitude and duration. The slow delayed rectifier, transient K+ currents, and membrane excitability were not affected by photoperiod. We conclude that photoperiod can change intrinsic ion channel properties of the SCN neurons, which may influence cellular communication and contribute to photoperiodic phase adjustment. PMID:27697884

  18. Photoperiod Modulates Fast Delayed Rectifier Potassium Currents in the Mammalian Circadian Clock.

    PubMed

    Farajnia, Sahar; Meijer, Johanna H; Michel, Stephan

    2016-10-01

    One feature of the mammalian circadian clock, situated in the suprachiasmatic nucleus (SCN), is its ability to measure day length and thereby contribute to the seasonal adaptation of physiology and behavior. The timing signal from the SCN, namely the 24 hr pattern of electrical activity, is adjusted according to the photoperiod being broader in long days and narrower in short days. Vasoactive intestinal peptide and gamma-aminobutyric acid play a crucial role in intercellular communication within the SCN and contribute to the seasonal changes in phase distribution. However, little is known about the underlying ionic mechanisms of synchronization. The present study was aimed to identify cellular mechanisms involved in seasonal encoding by the SCN. Mice were adapted to long-day (light-dark 16:8) and short-day (light-dark 8:16) photoperiods and membrane properties as well as K(+) currents activity of SCN neurons were measured using patch-clamp recordings in acute slices. Remarkably, we found evidence for a photoperiodic effect on the fast delayed rectifier K(+) current, that is, the circadian modulation of this ion channel's activation reversed in long days resulting in 50% higher peak values during the night compared with the unaltered day values. Consistent with fast delayed rectifier enhancement, duration of action potentials during the night was shortened and afterhyperpolarization potentials increased in amplitude and duration. The slow delayed rectifier, transient K(+) currents, and membrane excitability were not affected by photoperiod. We conclude that photoperiod can change intrinsic ion channel properties of the SCN neurons, which may influence cellular communication and contribute to photoperiodic phase adjustment.

  19. Calcium-dependent potassium current following penicillin-induced epileptiform discharges in the hippocampal slice.

    PubMed

    Domann, R; Dorn, T; Witte, O W

    1989-01-01

    Penicillin-induced paroxysmal depolarization shifts (PDS) are followed by prolonged afterhyperpolarizations of about 2 seconds duration. Intracellular injection of EGTA blocked a late component of the afterhyperpolarizations; an early one lasting up to one second was only slightly reduced by EGTA. It is concluded that afterhyperpolarizations following penicillin-induced PDS comprise different components: an initial one lasting up to one second which is not Ca2+-dependent and a slow one lasting up to two seconds which is caused by a Ca2+-dependent K+ current.

  20. Potassium currents in the heart: functional roles in repolarization, arrhythmia and therapeutics.

    PubMed

    Chiamvimonvat, Nipavan; Chen-Izu, Ye; Clancy, Colleen E; Deschenes, Isabelle; Dobrev, Dobromir; Heijman, Jordi; Izu, Leighton; Qu, Zhilin; Ripplinger, Crystal M; Vandenberg, Jamie I; Weiss, James N; Koren, Gideon; Banyasz, Tamas; Grandi, Eleonora; Sanguinetti, Michael C; Bers, Donald M; Nerbonne, Jeanne M

    2017-04-01

    This is the second of the two White Papers from the fourth UC Davis Cardiovascular Symposium Systems Approach to Understanding Cardiac Excitation-Contraction Coupling and Arrhythmias (3-4 March 2016), a biennial event that brings together leading experts in different fields of cardiovascular research. The theme of the 2016 symposium was 'K(+) channels and regulation', and the objectives of the conference were severalfold: (1) to identify current knowledge gaps; (2) to understand what may go wrong in the diseased heart and why; (3) to identify possible novel therapeutic targets; and (4) to further the development of systems biology approaches to decipher the molecular mechanisms and treatment of cardiac arrhythmias. The sessions of the Symposium focusing on the functional roles of the cardiac K(+) channel in health and disease, as well as K(+) channels as therapeutic targets, were contributed by Ye Chen-Izu, Gideon Koren, James Weiss, David Paterson, David Christini, Dobromir Dobrev, Jordi Heijman, Thomas O'Hara, Crystal Ripplinger, Zhilin Qu, Jamie Vandenberg, Colleen Clancy, Isabelle Deschenes, Leighton Izu, Tamas Banyasz, Andras Varro, Heike Wulff, Eleonora Grandi, Michael Sanguinetti, Donald Bers, Jeanne Nerbonne and Nipavan Chiamvimonvat as speakers and panel discussants. This article summarizes state-of-the-art knowledge and controversies on the functional roles of cardiac K(+) channels in normal and diseased heart. We endeavour to integrate current knowledge at multiple scales, from the single cell to the whole organ levels, and from both experimental and computational studies.

  1. A potassium current evoked by growth hormone-releasing hormone in follicular oocytes of Xenopus laevis.

    PubMed Central

    Yoshida, S; Plant, S

    1991-01-01

    1. Electrophysiological properties of the growth hormone-releasing hormone (GRH) receptor were studied in Xenopus oocytes with an intact follicle cell layer (i.e. follicular oocytes) by measuring whole-cell current using the two-electrode voltage-clamp method. 2. A slow transient outward current was elicited in oocytes, clamped at -60 mV, by the application of rat GRH but not bovine, porcine, or human GRH. 3. The response to GRH was not suppressed by blockers known to inhibit other endogenous receptors present in follicular Xenopus oocytes; blockers used were timolol (2 microM; beta-adrenergic blocker), theophylline (0.1 mM; purinergic blocker) and atropine (100 nM; muscarinic blocker). 4. The current response evoked by rat GRH occurred in a dose-dependent manner. The concentrations of GRH for threshold and maximum responses were 1 and 100 nM respectively and the estimated EC50 (half-maximal effective concentration) was approximately 7 nM. The amplitude and conductance of the response became larger and the latency, time-to-peak and half-decay time were shortened when the concentration of GRH was increased. 5. The GRH response was reversibly inhibited by a K+ channel blocker, tetraethylammonium+ (TEA+; 20 mM). The reversal potential for the GRH response was around -100 mV and was compatible with the reported value for a K+ current in Xenopus oocytes. Furthermore, a depolarizing shift of 40 mV in the reversal potential was observed when the external K+ concentration was increased from 2 to 10 mM, agreeing with the Nernst equation. In contrast, no significant shift in the reversal potential was observed by changing the external concentration of Na+ or Cl-. 6. The GRH response was not suppressed in oocytes treated with an acetoxy-methyl ester of bis-(o-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid (BAPTA/AM; 10 microM) which penetrates the cell membrane and chelates internal Ca2+. 7. The GRH response was potentiated by pre-treatment with forskolin (0.4 microM; 5 min

  2. Calcium-activated potassium current modulates ventricular repolarization in chronic heart failure.

    PubMed

    Bonilla, Ingrid M; Long, Victor P; Vargas-Pinto, Pedro; Wright, Patrick; Belevych, Andriy; Lou, Qing; Mowrey, Kent; Yoo, Jae; Binkley, Philip F; Fedorov, Vadim V; Györke, Sandor; Janssen, Paulus M L; Kilic, Ahmet; Mohler, Peter J; Carnes, Cynthia A

    2014-01-01

    The role of I(KCa) in cardiac repolarization remains controversial and varies across species. The relevance of the current as a therapeutic target is therefore undefined. We examined the cellular electrophysiologic effects of I(KCa) blockade in controls, chronic heart failure (HF) and HF with sustained atrial fibrillation. We used perforated patch action potential recordings to maintain intrinsic calcium cycling. The I(KCa) blocker (apamin 100 nM) was used to examine the role of the current in atrial and ventricular myocytes. A canine tachypacing induced model of HF (1 and 4 months, n = 5 per group) was used, and compared to a group of 4 month HF with 6 weeks of superimposed atrial fibrillation (n = 7). A group of age-matched canine controls were used (n = 8). Human atrial and ventricular myocytes were isolated from explanted end-stage failing hearts which were obtained from transplant recipients, and studied in parallel. Atrial myocyte action potentials were unchanged by I(KCa) blockade in all of the groups studied. I(KCa) blockade did not affect ventricular myocyte repolarization in controls. HF caused prolongation of ventricular myocyte action potential repolarization. I(KCa) blockade caused further prolongation of ventricular repolarization in HF and also caused repolarization instability and early afterdepolarizations. SK2 and SK3 expression in the atria and SK3 in the ventricle were increased in canine heart failure. We conclude that during HF, I(KCa) blockade in ventricular myocytes results in cellular arrhythmias. Furthermore, our data suggest an important role for I(KCa) in the maintenance of ventricular repolarization stability during chronic heart failure. Our findings suggest that novel antiarrhythmic therapies should have safety and efficacy evaluated in both atria and ventricles.

  3. Calcium-Activated Potassium Current Modulates Ventricular Repolarization in Chronic Heart Failure

    PubMed Central

    Bonilla, Ingrid M.; Long, Victor P.; Vargas-Pinto, Pedro; Wright, Patrick; Belevych, Andriy; Lou, Qing; Mowrey, Kent; Yoo, Jae; Binkley, Philip F.; Fedorov, Vadim V.; Györke, Sandor; Janssen, Paulus M. L.; Kilic, Ahmet; Mohler, Peter J.; Carnes, Cynthia A.

    2014-01-01

    The role of IKCa in cardiac repolarization remains controversial and varies across species. The relevance of the current as a therapeutic target is therefore undefined. We examined the cellular electrophysiologic effects of IKCa blockade in controls, chronic heart failure (HF) and HF with sustained atrial fibrillation. We used perforated patch action potential recordings to maintain intrinsic calcium cycling. The IKCa blocker (apamin 100 nM) was used to examine the role of the current in atrial and ventricular myocytes. A canine tachypacing induced model of HF (1 and 4 months, n = 5 per group) was used, and compared to a group of 4 month HF with 6 weeks of superimposed atrial fibrillation (n = 7). A group of age-matched canine controls were used (n = 8). Human atrial and ventricular myocytes were isolated from explanted end-stage failing hearts which were obtained from transplant recipients, and studied in parallel. Atrial myocyte action potentials were unchanged by IKCa blockade in all of the groups studied. IKCa blockade did not affect ventricular myocyte repolarization in controls. HF caused prolongation of ventricular myocyte action potential repolarization. IKCa blockade caused further prolongation of ventricular repolarization in HF and also caused repolarization instability and early afterdepolarizations. SK2 and SK3 expression in the atria and SK3 in the ventricle were increased in canine heart failure. We conclude that during HF, IKCa blockade in ventricular myocytes results in cellular arrhythmias. Furthermore, our data suggest an important role for IKCa in the maintenance of ventricular repolarization stability during chronic heart failure. Our findings suggest that novel antiarrhythmic therapies should have safety and efficacy evaluated in both atria and ventricles. PMID:25271970

  4. Asynchronous activation of calcium and potassium currents by isoproterenol in canine ventricular myocytes.

    PubMed

    Ruzsnavszky, Ferenc; Hegyi, Bence; Kistamás, Kornél; Váczi, Krisztina; Horváth, Balázs; Szentandrássy, Norbert; Bányász, Tamás; Nánási, Péter P; Magyar, János

    2014-05-01

    Adrenergic activation of L-type Ca(2+) and various K(+) currents is a crucial mechanism of cardiac adaptation; however, it may carry a substantial proarrhythmic risk as well. The aim of the present work was to study the timing of activation of Ca(2+) and K(+) currents in isolated canine ventricular cells in response to exposure to isoproterenol (ISO). Whole cell configuration of the patch-clamp technique in either conventional voltage clamp or action potential voltage clamp modes were used to monitor I(Ca), I(Ks), and I(Kr), while action potentials were recorded using sharp microelectrodes. ISO (10 nM) elevated the plateau potential and shortened action potential duration (APD) in subepicardial and mid-myocardial cells, which effects were associated with multifold enhancement of I(Ca) and I(Ks) and moderate stimulation of I(Kr). The ISO-induced plateau shift and I(Ca) increase developed faster than the shortening of APD and stimulation of I(Ks) and I(Kr). Blockade of β1-adrenoceptors (using 300 nM CGP-20712A) converted the ISO-induced shortening of APD to lengthening, decreased its latency, and reduced the plateau shift. In contrast, blockade of β2-adrenoceptors (by 50 nM ICI 118,551) augmented the APD-shortening effect and increased the latency of plateau shift without altering its magnitude. All effects of ISO were prevented by simultaneous blockade of both receptor types. Inhibition of phosphodiesterases decreased the differences observed in the turn on of the ISO-induced plateau shift and APD shortening. ISO-induced activation of I(Ca) is turned on faster than the stimulation of I(Ks) and I(Kr) in canine ventricular cells due to the involvement of different adrenergic pathways and compartmentalization.

  5. Small Conductance Calcium-Activated Potassium Current is Important in Transmural Repolarization of Failing Human Ventricles

    PubMed Central

    Yu, Chih-Chieh; Corr, Christopher; Shen, Changyu; Shelton, Richard; Yadava, Mrinal; Rhea, Isaac; Straka, Susan; Fishbein, Michael C.; Chen, Zhenhui; Lin, Shien-Fong; Lopshire, John C.; Chen, Peng-Sheng

    2015-01-01

    Background The transmural distribution of apamin-sensitive small conductance Ca2+-activated K+ (SK) current (IKAS) in failing human ventricles remains unclear. Methods and Results We optically mapped left ventricular wedge preparations from 12 failing native hearts and 2 rejected cardiac allografts explanted during transplant surgery. We determined transmural action potential duration (APD) before and after 100 nM apamin administration in all wedges and after sequential administration of apamin, chromanol and E4031 in 4 wedges. Apamin prolonged APD from 363 ms [95% confidence interval (CI), 341 to 385] to 409 [CI, 385 to 434] (p<0.001) in all hearts, and reduced the transmural conduction velocity from 36 cm/s [CI, 30 to 42] to 32 cm/s [CI, 27 to 37] (p=0.001) in 12 native failing hearts at 1000 ms pacing cycle length (PCL). The percent APD prolongation is negatively correlated with baseline APD and positively correlated with PCL. Only one wedge had M-cell islands. The percentages of APD prolongation in the last 4 hearts at 2000 ms PCL after apamin, chromanol and E4031 were 9.1% [CI, 3.9 to 14.2], 17.3% [CI, 3.1 to 31.5] and 35.9% [CI, 15.7 to 56.1], respectively. Immunohistochemical staining of subtype 2 of SK (SK2) protein showed increased expression in intercalated discs of myocytes. Conclusions SK current is important in the transmural repolarization in failing human ventricles. The magnitude of IKAS is positively correlated with the PCL, but negatively correlated with APD when PCL is fixed. There is abundant SK2 protein in the intercalated discs of myocytes. PMID:25908692

  6. Biophysical and pharmacological properties of the voltage-gated potassium current of human pancreatic β-cells

    PubMed Central

    Herrington, James; Sanchez, Manuel; Wunderler, Denize; Yan, Lizhen; Bugianesi, Randal M; Dick, Ivy E; Clark, Sam A; Brochu, Richard M; Priest, Birgit T; Kohler, Martin G; McManus, Owen B

    2005-01-01

    Voltage-gated potassium (Kv) currents of human pancreatic islet cells were studied by whole-cell patch clamp recording. On average, 75% of the cells tested were identified as β-cells by single cell, post-recording RT-PCR for insulin mRNA. In most cells, the dominant Kv current was a delayed rectifier. The delayed rectifier activated at potentials above −20 mV and had a V½ for activation of −5.3 mV. Onset of inactivation was slow for a major component (τ= 3.2 s at +20 mV) observed in all cells; a smaller component (τ= 0.30 s) with an amplitude of ∼25% was seen in some cells. Recovery from inactivation had a τ of 2.5 s at −80 mV and steady-state inactivation had a V½ of −39 mV. In 12% of cells (21/182) a low-threshold, transient Kv current (A-current) was present. The A-current activated at membrane potentials above −40 mV, inactivated with a time constant of 18.5 ms at −20 mV, and had a V½ for steady-state inactivation of −52 mV. TEA inhibited total Kv current with an IC50= 0.54 mm and PAC, a disubstituted cyclohexyl Kv channel inhibitor, inhibited with an IC50= 0.57 μm. The total Kv current was insensitive to margatoxin (100 nm), agitoxin-2 (50 nm), kaliotoxin (50 nm) and ShK (50 nm). Hanatoxin (100 nm) inhibited total Kv current by 65% at +20 mV. Taken together, these data provide evidence of at least two distinct types of Kv channels in human pancreatic β-cells and suggest that more than one type of Kv channel may be involved in the regulation of glucose-dependent insulin secretion. PMID:15932888

  7. Apamin Sensitive Potassium Current Modulates Action Potential Duration Restitution and Arrhythmogenesis of Failing Rabbit Ventricles

    PubMed Central

    Hsieh, Yu-Cheng; Chang, Po-Cheng; Hsueh, Chia-Hsiang; Lee, Young Soo; Shen, Changyu; Weiss, James N.; Chen, Zhenhui; Ai, Tomohiko; Lin, Shien-Fong; Chen, Peng-Sheng

    2013-01-01

    Background Apamin-sensitive K currents (IKAS) are upregulated in heart failure (HF). We hypothesize that apamin can flatten action potential duration restitution (APDR) curve and reduce ventricular fibrillation (VF) duration in failing ventricles. Methods and Results We simultaneously mapped membrane potential and intracellular Ca (Cai) in 7 rabbits hearts with pacing-induced HF and in 7 normal hearts. A dynamic pacing protocol was used to determine APDR at baseline and after apamin (100 nM) infusion. Apamin did not change APD80 in normal ventricles, but prolonged APD80 in failing ventricles at either long (≥300 ms) or short (≤170 ms) pacing cycle length (PCL), but not at intermediate PCL. The maximal slope of APDR curve was 2.03 [95% CI, 1.73 to 2.32] in failing ventricles and 1.26 [95% CI, 1.13 to 1.40] in normal ventricles at baseline (p=0.002). After apamin administration, the maximal slope of APDR in failing ventricles decreased to 1.43 [95% CI, 1.01 to 1.84] (p=0.018) whereas no significant changes were observed in normal ventricles. During VF in failing ventricles, the number of phase singularities (baseline vs apamin, 4.0 vs 2.5), dominant frequency (13.0 Hz vs 10.0 Hz), and VF duration (160 s vs 80 s) were all significantly (p<0.05) decreased by apamin. Conclusions Apamin prolongs APD at long and short, but not at intermediate PCL in failing ventricles. IKAS upregulation may be antiarrhythmic by preserving the repolarization reserve at slow heart rate, but is proarrhythmic by steepening the slope of APDR curve which promotes the generation and maintenance of VF. PMID:23420832

  8. Apamin-sensitive potassium current modulates action potential duration restitution and arrhythmogenesis of failing rabbit ventricles.

    PubMed

    Hsieh, Yu-Cheng; Chang, Po-Cheng; Hsueh, Chia-Hsiang; Lee, Young Soo; Shen, Changyu; Weiss, James N; Chen, Zhenhui; Ai, Tomohiko; Lin, Shien-Fong; Chen, Peng-Sheng

    2013-04-01

    Apamin-sensitive K currents (I(KAS)) are upregulated in heart failure. We hypothesize that apamin can flatten action potential duration restitution (APDR) curve and can reduce ventricular fibrillation duration in failing ventricles. We simultaneously mapped membrane potential and intracellular Ca (Ca(i)) in 7 rabbit hearts with pacing-induced heart failure and in 7 normal hearts. A dynamic pacing protocol was used to determine APDR at baseline and after apamin (100 nmol/L) infusion. Apamin did not change APD(80) in normal ventricles, but prolonged APD(80) in failing ventricles at either long (≥300 ms) or short (≤170 ms) pacing cycle length, but not at intermediate pacing cycle length. The maximal slope of APDR curve was 2.03 (95% confidence interval, 1.73-2.32) in failing ventricles and 1.26 (95% confidence interval, 1.13-1.40) in normal ventricles at baseline (P=0.002). After apamin administration, the maximal slope of APDR in failing ventricles decreased to 1.43 (95% confidence interval, 1.01-1.84; P=0.018), whereas no significant changes were observed in normal ventricles. During ventricular fibrillation in failing ventricles, the number of phase singularities (baseline versus apamin, 4.0 versus 2.5), dominant frequency (13.0 versus 10.0 Hz), and ventricular fibrillation duration (160 versus 80 s) were all significantly (P<0.05) decreased by apamin. Apamin prolongs APD at long and short, but not at intermediate pacing cycle length in failing ventricles. I(KAS) upregulation may be antiarrhythmic by preserving the repolarization reserve at slow heart rate, but is proarrhythmic by steepening the slope of APDR curve, which promotes the generation and maintenance of ventricular fibrillation.

  9. Heterogeneous Upregulation of Apamin‐Sensitive Potassium Currents in Failing Human Ventricles

    PubMed Central

    Chang, Po‐Cheng; Turker, Isik; Lopshire, John C.; Masroor, Saqib; Nguyen, Bich‐Lien; Tao, Wen; Rubart, Michael; Chen, Peng‐Sheng; Chen, Zhenhui; Ai, Tomohiko

    2013-01-01

    Background We previously reported that IKAS are heterogeneously upregulated in failing rabbit ventricles and play an important role in arrhythmogenesis. This study goal is to test the hypothesis that subtype 2 of the small‐conductance Ca2+ activated K+ (SK2) channel and apamin‐sensitive K+ currents (IKAS) are upregulated in failing human ventricles. Methods and Results We studied 12 native hearts from transplant recipients (heart failure [HF] group) and 11 ventricular core biopsies from patients with aortic stenosis and normal systolic function (non‐HF group). IKAS and action potential were recorded with patch‐clamp techniques, and SK2 protein expression was studied by Western blotting. When measured at 1 μmol/L Ca2+ concentration, IKAS was 4.22 (median) (25th and 75th percentiles, 2.86 and 6.96) pA/pF for the HF group (n=11) and 0.98 (0.54 and 1.72) pA/pF for the non‐HF group (n=8, P=0.008). IKAS was lower in the midmyocardial cells than in the epicardial and the endocardial cells. The Ca2+ dependency of IKAS in HF myocytes was shifted leftward compared to non‐HF myocytes (Kd 314 versus 605 nmol/L). Apamin (100 nmol/L) increased the action potential durations by 1.77% (−0.9% and 7.3%) in non‐HF myocytes and by 11.8% (5.7% and 13.9%) in HF myocytes (P=0.02). SK2 protein expression was 3‐fold higher in HF than in non‐HF. Conclusions There is heterogeneous upregulation of IKAS densities in failing human ventricles. The midmyocardial layer shows lower IKAS densities than epicardial and endocardial layers of cells. Increase in both Ca2+ sensitivity and SK2 protein expression contributes to the IKAS upregulation. PMID:23525437

  10. Systemic Effects of Ingested Lactobacillus Rhamnosus: Inhibition of Mast Cell Membrane Potassium (IKCa) Current and Degranulation

    PubMed Central

    Forsythe, Paul; Wang, Binxiang; Khambati, Ibrahim; Kunze, Wolfgang A.

    2012-01-01

    Exposure of the intestine to certain strains lactobacillus can have systemic immune effects that include the attenuation of allergic responses. Despite the central role of mast cells in allergic disease little is known about the effect of lactobacilli on the function of these cells. To address this we assessed changes in rat mast cell activation following oral treatment with a strain of Lactobacillus known to attenuate allergic responses in animal models. Sprague Dawley rats were fed with L.rhamnosus JB-1 (1×109) or vehicle control for 9 days. Mediator release from peritoneal mast cells (RPMC) was determined in response to a range of stimuli. Passive cutaneous anaphylaxis (PCA) was used to assess mast cell responses in vivo. The Ca2+ activated K+ channel (KCa3.1) current, identified as critical to mast cell degranulation, was monitored by whole cell patch-clamp. L.rhamnosus JB-1 treatment lead to significant inhibition of mast cell mediator release in response to a range of stimuli including IgE mediated activation. Furthermore, the PCA response was significantly reduced in treated rats. Patch-clamp studies revealed that RPMC from treated animals were much less responsive to the KCa3.1 opener, DCEBIO. These studies demonstrate that Ingestion of L.rhamnosus JB-1 leads to mast cell stabilization in rats and identify KCa3.1 as an immunomodulatory target for certain lactobacilli. Thus the systemic effects of certain candidate probiotics may include mast cell stabilization and such actions could contribute to the beneficial effect of these organisms in allergic and other inflammatory disorders. PMID:22815978

  11. Frequently Asked Questions on Potassium Iodide (KI)

    MedlinePlus

    ... needs to take potassium iodide (KI) after a nuclear radiation release? What potassium iodide (KI) products are currently ... needs to take potassium iodide (KI) after a nuclear radiation release? The FDA guidance prioritizes groups based on ...

  12. Role of the Excitability Brake Potassium Current IKD in Cold Allodynia Induced by Chronic Peripheral Nerve Injury.

    PubMed

    González, Alejandro; Ugarte, Gonzalo; Restrepo, Carlos; Herrera, Gaspar; Piña, Ricardo; Gómez-Sánchez, José Antonio; Pertusa, María; Orio, Patricio; Madrid, Rodolfo

    2017-03-22

    Cold allodynia is a common symptom of neuropathic and inflammatory pain following peripheral nerve injury. The mechanisms underlying this disabling sensory alteration are not entirely understood. In primary somatosensory neurons, cold sensitivity is mainly determined by a functional counterbalance between cold-activated TRPM8 channels and Shaker-like Kv1.1-1.2 channels underlying the excitability brake current IKD Here we studied the role of IKD in damage-triggered painful hypersensitivity to innocuous cold. We found that cold allodynia induced by chronic constriction injury (CCI) of the sciatic nerve in mice, was related to both an increase in the proportion of cold-sensitive neurons (CSNs) in DRGs contributing to the sciatic nerve, and a decrease in their cold temperature threshold. IKD density was reduced in high-threshold CSNs from CCI mice compared with sham animals, with no differences in cold-induced TRPM8-dependent current density. The electrophysiological properties and neurochemical profile of CSNs revealed an increase of nociceptive-like phenotype among neurons from CCI animals compared with sham mice. These results were validated using a mathematical model of CSNs, including IKD and TRPM8, showing that a reduction in IKD current density shifts the thermal threshold to higher temperatures and that the reduction of this current induces cold sensitivity in former cold-insensitive neurons expressing low levels of TRPM8-like current. Together, our results suggest that cold allodynia is largely due to a functional downregulation of IKD in both high-threshold CSNs and in a subpopulation of polymodal nociceptors expressing TRPM8, providing a general molecular and neural mechanism for this sensory alteration.SIGNIFICANCE STATEMENT This paper unveils the critical role of the brake potassium current IKD in damage-triggered cold allodynia. Using a well-known form of nerve injury and combining behavioral analysis, calcium imaging, patch clamping, and pharmacological

  13. Modulation of Kv3 subfamily potassium currents by the sea anemone toxin BDS: significance for CNS and biophysical studies.

    PubMed

    Yeung, Shuk Yin M; Thompson, Dawn; Wang, Zhuren; Fedida, David; Robertson, Brian

    2005-09-21

    Kv3 potassium channels, with their ultra-rapid gating and high activation threshold, are essential for high-frequency firing in many CNS neurons. Significantly, the Kv3.4 subunit has been implicated in the major CNS disorders Parkinson's and Alzheimer's diseases, and it is claimed that selectively targeting this subunit will have therapeutic utility. Previous work suggested that BDS toxins ("blood depressing substance," from the sea anemone Anemonia sulcata) were specific blockers for rapidly inactivating Kv3.4 channels, and consequently these toxins are increasingly used as diagnostic agents for Kv3.4 subunits in central neurons. However, precisely how selective are these toxins for this important CNS protein? We show that BDS is not selective for Kv3.4 but markedly inhibits current through Kv3.1 and Kv3.2 channels. Inhibition comes about not by "pore block" but by striking modification of Kv3 gating kinetics and voltage dependence. Activation and inactivation kinetics are slowed by BDS-I and BDS-II, and V(1/2) for activation is shifted to more positive voltages. Alanine substitution mutagenesis around the S3b and S4 segments of Kv3.2 reveals that BDS acts via voltage-sensing domains, and, consistent with this, ON gating currents from nonconducting Kv3.2 are markedly inhibited. The altered kinetics and gating properties, combined with lack of subunit selectivity with Kv3 subunits, seriously affects the usefulness of BDS toxins in CNS studies. Furthermore, our results do not easily fit with the voltage sensor "paddle" structure proposed recently for Kv channels. Our data will be informative for experiments designed to dissect out the roles of Kv3 subunits in CNS function and dysfunction.

  14. The role of ERK-1/2 in the N/OFQ-induced inhibition of delayed rectifier potassium currents

    SciTech Connect

    Wang, Wei; Cui, Qingbo; Li, Yurong; Li, Baoxin; Yang, Xu; Cui, Lanwei; Jin, Hongbo; Qu, Lihui

    2010-04-16

    Nociceptin/orphanin FQ (N/OFQ) is an endogenous opioid-like heptadecapeptide involved in many neurocognitive functions, including learning and memory. Our previous report showed that N/OFQ inhibits the delayed rectifier potassium current (I{sub K}), and this effect is associated with protein kinase C (PKC) activation. Therefore, we wanted to determine if extracellular signal-regulated kinase-1/2 (ERK-1/2) signaling is regulated by N/OFQ and associated with the effect of N/OFQ on the I{sub K}. In the current study, we tested if N/OFQ and two PKC activators [phorbol 12,13-dibutyrate (PDBu) and ingenol 3,20-dibenzoate (IDB)] affected the phosphorylation level of ERK-1/2 and its nuclear substrate, ETS-like transcription factor-1 (Elk-1), using western blots. In addition, we tested if ERK-1/2 affected the N/OFQ-induced inhibition of the I{sub K} by using whole-cell patch-clamp recordings in acutely dissociated rat parietal cortical neurons. We found that N/OFQ, PDBu, and IDB increased the amount of phosphorylated ERK-1/2 and Elk-1; U0126, a specific inhibitor for ERK-1/2, attenuated the inhibitory effect of N/OFQ on the I{sub K}. These data suggest that the ERK-1/2 pathway, at least in part, mediates the inhibitory effect of N/OFQ on the I{sub K} in acutely dissociated rat cerebral parietal cortical neurons.

  15. Functional coupling between sodium-activated potassium channels and voltage-dependent persistent sodium currents in cricket Kenyon cells.

    PubMed

    Takahashi, Izumi; Yoshino, Masami

    2015-10-01

    In this study, we examined the functional coupling between Na(+)-activated potassium (KNa) channels and Na(+) influx through voltage-dependent Na(+) channels in Kenyon cells isolated from the mushroom body of the cricket Gryllus bimaculatus. Single-channel activity of KNa channels was recorded with the cell-attached patch configuration. The open probability (Po) of KNa channels increased with increasing Na(+) concentration in a bath solution, whereas it decreased by the substitution of Na(+) with an equimolar concentration of Li(+). The Po of KNa channels was also found to be reduced by bath application of a high concentration of TTX (1 μM) and riluzole (100 μM), which inhibits both fast (INaf) and persistent (INaP) Na(+) currents, whereas it was unaffected by a low concentration of TTX (10 nM), which selectively blocks INaf. Bath application of Cd(2+) at a low concentration (50 μM), as an inhibitor of INaP, also decreased the Po of KNa channels. Conversely, bath application of the inorganic Ca(2+)-channel blockers Co(2+) and Ni(2+) at high concentrations (500 μM) had little effect on the Po of KNa channels, although Cd(2+) (500 μM) reduced the Po of KNa channels. Perforated whole cell clamp analysis further indicated the presence of sustained outward currents for which amplitude was dependent on the amount of Na(+) influx. Taken together, these results indicate that KNa channels could be activated by Na(+) influx passing through voltage-dependent persistent Na(+) channels. The functional significance of this coupling mechanism was discussed in relation to the membrane excitability of Kenyon cells and its possible role in the formation of long-term memory. Copyright © 2015 the American Physiological Society.

  16. Modulation of Kv3 Subfamily Potassium Currents by the Sea Anemone Toxin BDS: Significance for CNS and Biophysical Studies

    PubMed Central

    Yeung, Shuk Yin M.; Thompson, Dawn; Wang, Zhuren; Fedida, David; Robertson, Brian

    2005-01-01

    Kv3 potassium channels, with their ultra-rapid gating and high activation threshold, are essential for high-frequency firing in many CNS neurons. Significantly, the Kv3.4 subunit has been implicated in the major CNS disorders Parkinson’s and Alzheimer’s diseases, and it is claimed that selectively targeting this subunit will have therapeutic utility. Previous work suggested that BDS toxins (“blood depressing substance,” from the sea anemone Anemonia sulcata) were specific blockers for rapidly inactivating Kv3.4 channels, and consequently these toxins are increasingly used as diagnostic agents for Kv3.4 subunits in central neurons. However, precisely how selective are these toxins for this important CNS protein? We show that BDS is not selective for Kv3.4 but markedly inhibits current through Kv3.1 and Kv3.2 channels. Inhibition comes about not by “pore block” but by striking modification of Kv3 gating kinetics and voltage dependence. Activation and inactivation kinetics are slowed by BDS-I and BDS-II, and V1/2 for activation is shifted to more positive voltages. Alanine substitution mutagenesis around the S3b and S4 segments of Kv3.2 reveals that BDS acts via voltage-sensing domains, and, consistent with this, ON gating currents from nonconducting Kv3.2 are markedly inhibited. The altered kinetics and gating properties, combined with lack of subunit selectivity with Kv3 subunits, seriously affects the usefulness of BDS toxins in CNS studies. Furthermore, our results do not easily fit with the voltage sensor “paddle” structure proposed recently for Kv channels. Our data will be informative for experiments designed to dissect out the roles of Kv3 subunits in CNS function and dysfunction. PMID:16177043

  17. The modulatory effect of zinc ions on voltage-gated potassium currents in cultured rat hippocampal neurons is not related to Kv1.3 channels.

    PubMed

    Teisseyre, A; Mercik, K; Mozrzymas, J W

    2007-12-01

    We applied the whole-cell patch-clamp technique to study the influence of zinc ions (Zn(2+)) and extracellular protons at acidic pH (pH(o)) on voltage-gated potassium currents in cultured rat hippocampal neurons. The first goal of the study was to estimate whether Kv1.3 currents significantly contributed to voltage-gated potassium currents in examined cells. Then, the influence of both ions on the activity of other voltage-gated potassium currents in the neurons was examined. We examined both the total current and the delayed - rectifier component. Results obtained in both cases were not significantly different from each other. Available data argued against any significant contribution of Kv1.3 currents to the recorded currents. Nevertheless, application of Zn(2+) in the concentration range from 100 microM to 5 mM reversibly modulated the recorded currents. The activation midpoint was shifted by about 40 mV (total current) and 30 mV (delayed-rectifier current) towards positive membrane potentials and the activation kinetics were slowed significantly (2 - 3 fold) upon application of Zn(2+). The inactivation midpoint was also shifted towards positive membrane potentials, but less significantly (about 14 mV). The current amplitudes were reduced in a concentration-dependent manner to about 0.5 of the control value. The effects of Zn(2+) were saturated at the concentration of 1 mM. Raising extracellular proton concentration by lowering the pH(o) from 7.35 to 6.4 did not affect significantly the currents. Possible mechanisms underlying the observed phenomena and their possible physiological significance are discussed.

  18. The role of potassium and sodium-calcium exchange currents in the action potential durations of normal Purkinje fibres and Purkinje fibres surviving infarction.

    PubMed

    Bril, A; Man, R Y

    1989-05-01

    Ventricular arrhythmias following myocardial infarction may originate from subendocardial Purkinje fibres in the infarcted area. The role of potassium and sodium-calcium exchange currents on action potential duration was therefore investigated in Purkinje fibres surviving infarction and in normal Purkinje fibres. Barium was used to reduce potassium conductance and replacement of sodium chloride by lithium chloride was used to reduce the sodium-calcium exchange current. Barium (1 x 10(-5) to 3 x 10(-5) M) produced a concentration dependent lengthening of action potential duration in normal Purkinje fibres but these concentrations had no effect in Purkinje fibres surviving infarction. The resting membrane potential, activation voltage, amplitude and Vmax were decreased in Purkinje fibres surviving infarction and in barium treated fibres v normal Purkinje fibres. These results show that action potential characteristics of barium treated normal Purkinje fibres closely resemble those seen in Purkinje fibres surviving infarction. A similar reduction of action potential duration was seen in normal Purkinje fibres, fibres surviving infarction and barium treated fibres when the sodium "window" current was decreased by lignocaine. Without any effect on the Vmax, the replacement of sodium chloride by lithium chloride resulted in a similar effect on the action potential duration in normal Purkinje fibres and fibres surviving infarction. The results show that the longer action potential duration found in Purkinje fibres surviving infarction can be explained by a decrease of the potassium conductance and not by an increase of the sodium "window" current or the sodium-calcium exchange current.

  19. 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 (Ito ) 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 Ito 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 (APD90 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; APD90 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 Ito was significantly decreased at the 4(th) day after cardiac transplantation. The APD of

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

    PubMed Central

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

    2017-01-01

    Background 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 (Ito) in cardiomyocytes during acute cardiac rejection. Methods 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 4th 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 Ito current were recorded using the whole cell patch-clamp technique. Results Forty grafted hearts were successfully harvested and used in experiments. Histologic examination showed mild rejection at the 2nd day and moderate rejection at the 4th 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 (APD90 was 49.28±5.621 mV in the isogeneic group and 88.08±6.445 mV in the allogeneic group at the 2nd day, P=0.0016; APD90 was 59.34±5.183 mV in the isogeneic group and 104.0±9.523 mV in the allogeneic group at the 4th day, P=0.0064). The current density of Ito was significantly decreased at the 4th day after cardiac transplantation

  1. Constitutively Active Acetylcholine-Dependent Potassium Current Increases Atrial Defibrillation Threshold by Favoring Post-Shock Re-Initiation.

    PubMed

    Bingen, Brian O; Askar, Saïd F A; Neshati, Zeinab; Feola, Iolanda; Panfilov, Alexander V; de Vries, Antoine A F; Pijnappels, Daniël A

    2015-10-21

    Electrical cardioversion (ECV), a mainstay in atrial fibrillation (AF) treatment, is unsuccessful in up to 10-20% of patients. An important aspect of the remodeling process caused by AF is the constitutive activition of the atrium-specific acetylcholine-dependent potassium current (IK,ACh → IK,ACh-c), which is associated with ECV failure. This study investigated the role of IK,ACh-c in ECV failure and setting the atrial defibrillation threshold (aDFT) in optically mapped neonatal rat cardiomyocyte monolayers. AF was induced by burst pacing followed by application of biphasic shocks of 25-100 V to determine aDFT. Blocking IK,ACh-c by tertiapin significantly decreased DFT, which correlated with a significant increase in wavelength during reentry. Genetic knockdown experiments, using lentiviral vectors encoding a Kcnj5-specific shRNA to modulate IK,ACh-c, yielded similar results. Mechanistically, failed ECV was attributed to incomplete phase singularity (PS) removal or reemergence of PSs (i.e. re-initiation) through unidirectional propagation of shock-induced action potentials. Re-initiation occurred at significantly higher voltages than incomplete PS-removal and was inhibited by IK,ACh-c blockade. Whole-heart mapping confirmed our findings showing a 60% increase in ECV success rate after IK,ACh-c blockade. This study provides new mechanistic insight into failing ECV of AF and identifies IK,ACh-c as possible atrium-specific target to increase ECV effectiveness, while decreasing its harmfulness.

  2. Constitutively Active Acetylcholine-Dependent Potassium Current Increases Atrial Defibrillation Threshold by Favoring Post-Shock Re-Initiation

    PubMed Central

    Bingen, Brian O.; Askar, Saïd F. A.; Neshati, Zeinab; Feola, Iolanda; Panfilov, Alexander V.; de Vries, Antoine A. F.; Pijnappels, Daniël A.

    2015-01-01

    Electrical cardioversion (ECV), a mainstay in atrial fibrillation (AF) treatment, is unsuccessful in up to 10–20% of patients. An important aspect of the remodeling process caused by AF is the constitutive activition of the atrium-specific acetylcholine-dependent potassium current (IK,ACh → IK,ACh-c), which is associated with ECV failure. This study investigated the role of IK,ACh-c in ECV failure and setting the atrial defibrillation threshold (aDFT) in optically mapped neonatal rat cardiomyocyte monolayers. AF was induced by burst pacing followed by application of biphasic shocks of 25–100 V to determine aDFT. Blocking IK,ACh-c by tertiapin significantly decreased DFT, which correlated with a significant increase in wavelength during reentry. Genetic knockdown experiments, using lentiviral vectors encoding a Kcnj5-specific shRNA to modulate IK,ACh-c, yielded similar results. Mechanistically, failed ECV was attributed to incomplete phase singularity (PS) removal or reemergence of PSs (i.e. re-initiation) through unidirectional propagation of shock-induced action potentials. Re-initiation occurred at significantly higher voltages than incomplete PS-removal and was inhibited by IK,ACh-c blockade. Whole-heart mapping confirmed our findings showing a 60% increase in ECV success rate after IK,ACh-c blockade. This study provides new mechanistic insight into failing ECV of AF and identifies IK,ACh-c as possible atrium-specific target to increase ECV effectiveness, while decreasing its harmfulness. PMID:26487066

  3. Chronic enalapril treatment increases transient outward potassium current in cardiomyocytes isolated from right ventricle of spontaneously hypertensive rats.

    PubMed

    Rodrigues Junior, Luiz Fernando; de Azevedo Carvalho, Ana Carolina; Pimentel, Enildo Broetto; Mill, José Geraldo; Nascimento, José Hamilton Matheus

    2017-03-01

    It has been well established that chronic pressure overload resulting from hypertension leads to ventricular hypertrophy and electrophysiological remodeling. The transient outward potassium current (I to) reduction described in hypertensive animals delays ventricular repolarization, leading to complex ventricular arrhythmias and sudden death. Antihypertensive drugs, as angiotensin-converting enzyme inhibitors (ACEi), can restore I to and reduce the incidence of arrhythmic events. The purpose of this study was to evaluate the differential effects of long-term treatment with ACEi or direct-acting smooth muscle relaxant on the I to of left and right ventricle myocytes of spontaneously hypertensive rats (SHR). Animals were divided into four groups: normotensive Wistar-Kyoto rats (WKY), hypertensive (SHR), SHR treated for 6 weeks with enalapril 10 mg/kg/day (SHRE), or hydralazine 20 mg/kg/day (SHRH). Systolic blood pressure (SBP) and hypertrophy index (heart weight/body weight (HW/BW)) were determined at the end of treatment period. Cell membrane capacitance (C m) and I to were assessed in cardiomyocytes isolated from left and right ventricles. The SHR exhibited significantly increased SBP and HW/BW when compared to the WKY. The treated groups, SHRE and SHRH, restored normal SBP but not HW/BW. The SHR group exhibited a diminished I to in the left but not the right ventricle. Both the treated groups restored I to in the left ventricle. However, in the right ventricle, only enalapril treatment modified I to. The SHRE group exhibited a significant increase in I to compared to all the other groups. These findings suggest that enalapril may increase I to by a pressure overload independent mechanism.

  4. ATP-sensitive potassium currents from channels formed by Kir6 and a modified cardiac mitochondrial SUR2 variant

    PubMed Central

    Aggarwal, Nitin T; Shi, Nian-Qing; Makielski, Jonathan C

    2013-01-01

    Cardiac ATP-sensitive potassium channels (KATP) are found in both the sarcoplasmic reticulum (sarcKATP) and the inner membrane of mitochondria (mitoKATP). SarcKATP are composed of a pore containing subunit Kir6.2 and a regulatory sulfonylurea receptor subunit (SUR2), but the composition of mitoKATP remains unclear. An unusual intra-exonic splice variant of SUR2 (SUR2A-55) was previously identified in mitochondria of mammalian heart and brain, and by analogy with sarcKATP we proposed SUR2A-55 as a candidate regulatory subunit of mitoKATP. Although SUR2A-55 lacks the first nucleotide binding domain (NBD) and 2 transmembrane domains (TMD), it has a hybrid TMD and retains the second NBD. It resembles a hemi-ABC transporter suggesting it could multimerize to function as a regulatory subunit. A putative mitochondrial targeting signal in the N-terminal domain of SUR2A-55 was removed by truncation and when co-expressed with Kir6.1 and Kir6.2 it targeted to the plasma membrane and yielded KATP currents. Single channel conductance, mean open time, and burst open time of SUR2A-55 based KATP was similar to the full-length SUR2A based KATP. However, the SUR2A-55 KATP were 70-fold less sensitive to block by ATP, and twice as resistant to intracellular Ca2+ inhibition compared with the SUR2A KATP, and were markedly insensitive to KATP drugs, pinacidil, diazoxide, and glybenclamide. These results suggest that the SUR2A-55 based channels would tend to be open under physiological conditions and in ischemia, and could account for cardiac and mitochondrial phenotypes protective for ischemia. PMID:24037327

  5. Interleukin-1R3 mediates interleukin-1-induced potassium current increase through fast activation of Akt kinase.

    PubMed

    Qian, Jiang; Zhu, Ling; Li, Qiming; Belevych, Natalya; Chen, Qun; Zhao, Fangli; Herness, Scott; Quan, Ning

    2012-07-24

    Inflammatory cytokine interleukin-1 (IL-1) performs multiple functions in the central nervous system. The type 1 IL-1 receptor (IL-1R1) and the IL-1 receptor accessory protein (IL-1RAcP) form a functional IL-1 receptor complex that is thought to mediate most, if not all, IL-1-induced effects. Several recent studies, however, suggest the existence of a heretofore-unidentified receptor for IL-1. In this study, we report that the IL-1R1 gene contains an internal promoter that drives the transcription of a shortened IL-1R1 mRNA. This mRNA is the template for a unique IL-1R protein that is identical to IL-1R1 at the C terminus, but with a shorter extracellular domain at the N terminus. We have termed this molecule IL-1R3. The mRNA and protein for IL-1R3 are expressed in normal and two strains of commercially available IL-1R1 knockout mice. Western blot analysis shows IL-1R3 is preferentially expressed in neural tissues. Furthermore, IL-1β binds specifically to IL-1R3 when it is complexed with the newly discovered alternative IL-1 receptor accessory protein, IL-1RAcPb. Stimulation of neurons expressing both IL-1R3 and IL-1RAcPb with IL-1β causes fast activation of the Akt kinase, which leads to an increase in voltage-gated potassium current. These results demonstrate that IL-1R3/IL-1RAcPb complex mediates a unique subset of IL-1 activity that accounts for many previously unexplained IL-1 effects in the central nervous system.

  6. Interleukin-1R3 mediates interleukin-1–induced potassium current increase through fast activation of Akt kinase

    PubMed Central

    Qian, Jiang; Zhu, Ling; Li, Qiming; Belevych, Natalya; Chen, Qun; Zhao, Fangli; Herness, Scott; Quan, Ning

    2012-01-01

    Inflammatory cytokine interleukin-1 (IL-1) performs multiple functions in the central nervous system. The type 1 IL-1 receptor (IL-1R1) and the IL-1 receptor accessory protein (IL-1RAcP) form a functional IL-1 receptor complex that is thought to mediate most, if not all, IL-1–induced effects. Several recent studies, however, suggest the existence of a heretofore-unidentified receptor for IL-1. In this study, we report that the IL-1R1 gene contains an internal promoter that drives the transcription of a shortened IL-1R1 mRNA. This mRNA is the template for a unique IL-1R protein that is identical to IL-1R1 at the C terminus, but with a shorter extracellular domain at the N terminus. We have termed this molecule IL-1R3. The mRNA and protein for IL-1R3 are expressed in normal and two strains of commercially available IL-1R1 knockout mice. Western blot analysis shows IL-1R3 is preferentially expressed in neural tissues. Furthermore, IL-1β binds specifically to IL-1R3 when it is complexed with the newly discovered alternative IL-1 receptor accessory protein, IL-1RAcPb. Stimulation of neurons expressing both IL-1R3 and IL-1RAcPb with IL-1β causes fast activation of the Akt kinase, which leads to an increase in voltage-gated potassium current. These results demonstrate that IL-1R3/IL-1RAcPb complex mediates a unique subset of IL-1 activity that accounts for many previously unexplained IL-1 effects in the central nervous system. PMID:22778412

  7. Potassium test

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/003484.htm Potassium test To use the sharing features on this ... enable JavaScript. This test measures the amount of potassium in the fluid portion (serum) of the blood. ...

  8. Action of niflumic acid on evoked and spontaneous calcium-activated chloride and potassium currents in smooth muscle cells from rabbit portal vein.

    PubMed Central

    Hogg, R. C.; Wang, Q.; Large, W. A.

    1994-01-01

    1. The action of niflumic acid was studied on spontaneous and evoked calcium-activated chloride (ICl(Ca)) and potassium (IK(Ca)) currents in rabbit isolated portal vein cells. 2. With the nystatin perforated patch technique in potassium-containing solutions at a holding potential of -77 mV (the potassium equilibrium potential), niflumic acid produced a concentration-dependent inhibition of spontaneous transient inward current (STIC, calcium-activated chloride current) amplitude. The concentration to reduce the STIC amplitude by 50% (IC50) was 3.6 x 10(-6) M. 3. At -77 mV holding potential, niflumic acid converted the STIC decay from a single exponential to 2 exponential components. In niflumic acid the fast component of decay was faster, and the slow component was slower than the control decay time constant. Increasing the concentration of niflumic acid enhanced the decay rate of the fast component and reduced the decay rate of the slow component. 4. The effect of niflumic acid on STIC amplitude was voltage-dependent and at -50 and +50 mV the IC50 values were 2.3 x 10(-6) M and 1.1 x 10(-6) M respectively (cf. 3.6 x 10(-6) M at -77 mV). 5. In K-free solutions at potentials of -50 mV and +50 mV, niflumic acid did not induce a dual exponential STIC decay but just increased the decay time constant at both potentials in a concentration-dependent manner. 6. Niflumic acid, in concentrations up to 5 x 10(-5) M, had no effect on spontaneous calcium-activated potassium currents.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7921628

  9. Comparison of the pinning and the bulk currents in the critical state of a type-II superconductor

    NASA Astrophysics Data System (ADS)

    Krasnov, V. M.; Ryazanov, V. V.

    1998-03-01

    The bulk current density distribution in the critical state of a type-II superconductor is studied for different pinning strengths and external magnetic fields. The calculations were made within the extended critical state model for a three-axis ellipsoid, taking into account the equilibrium vortex lattice magnetization caused by the vortex interaction. It is shown that the average current density, Jav, could be considerably different from the critical pinning current density, Jc, for the magnetic fields not much larger than the lower critical field Hc1. The difference between Jav and Jc result in additional curvature of the local magnetic field profiles and modifies the total moment of the sample which might be important for the analysis of various magnetization experiments.

  10. Effects of phospholipase A2 inhibitors on coupling of alpha 2-adrenoceptors to inwardly rectifying potassium currents in guinea-pig submucosal neurones.

    PubMed Central

    Evans, R. J.; Surprenant, A.

    1993-01-01

    1. Noradrenaline hyperpolarizes guinea-pig submucosal neurones by opening inwardly rectifying potassium channels. Intracellular recordings were made from submucosal neurones and the possible involvement of the phospholipase A2 pathway in this response was examined. 2. The non-specific phospholipase A2 inhibitors, quinacrine (10 microM) and 4-bromophenacyl bromide (4-BPB, 10 microM) inhibited nerve-evoked inhibitory synaptic potentials (i.p.s.ps) and hyperpolarizations to somatostatin and UK 14304. Quinacrine and 4-BPB also blocked the inward rectification present in current-voltage curves in the absence of somatostatin or UK 14304. 3. The more selective phospholipase A2 inhibitor, cyclosporin A (10 microM) and the lipoxygenase and cyclo-oxygenase inhibitor, eicosatetraynoic acid (ETYA, 20 microM) and nordihydroguairetic acid (NDGA, 20 microM) did not alter i.p.s.ps or hyperpolarizations to UK 14304. 4. Exogenously applied arachidonic acid (1-300 microM) did not mimic the i.p.s.p. or the hyperpolarization to UK 14304. 5. We conclude that arachidonic acid or its eicosanoid metabolites produced by phospholipase A2 stimulation are unlikely to be involved in the receptor G-protein coupled activation of potassium currents in submucosal neurones. The inhibition of the noradrenaline-induced hyperpolarization by quinacrine and 4-BPB is most likely due primarily to blockade of the basal inwardly rectifying potassium conductance present in these neurones. PMID:7902174

  11. Theory of flux cutting and flux transport at the critical current of a type-II superconducting cylindrical wire

    NASA Astrophysics Data System (ADS)

    Clem, John R.

    2011-06-01

    I introduce a critical-state theory incorporating both flux cutting and flux transport to calculate the magnetic-field and current-density distributions inside a type-II superconducting cylinder at its critical current in a longitudinal applied magnetic field. The theory is an extension of the elliptic critical-state model introduced by Romero-Salazar and Pérez-Rodríguez. The vortex dynamics depend in detail on two nonlinear effective resistivities for flux cutting (ρ∥) and flux flow (ρ⊥), and their ratio r=ρ∥/ρ⊥. When r<1, the low relative efficiency of flux cutting in reducing the magnitude of the internal magnetic-flux density leads to a paramagnetic longitudinal magnetic moment. As a model for understanding the experimentally observed interrelationship between the critical currents for flux cutting and depinning, I calculate the forces on a helical vortex arc stretched between two pinning centers when the vortex is subjected to a current density of arbitrary angle ϕ. Simultaneous initiation of flux cutting and flux transport occurs at the critical current density Jc(ϕ) that makes the vortex arc unstable.

  12. Histamine H1 receptor activation blocks two classes of potassium current, IK(rest) and IAHP, to excite ferret vagal afferents.

    PubMed Central

    Jafri, M S; Moore, K A; Taylor, G E; Weinreich, D

    1997-01-01

    1. Intracellular recordings were made in intact and acutely dissociated vagal afferent neurones (nodose ganglion cells) of the ferret to investigate the membrane effects of histamine. 2. In current-clamp or voltage-clamp recordings, histamine (10 microM) depolarized the membrane potential (10 +/- 0.8 mV; mean +/- S.E.M.; n = 27) or produced an inward current of 1.6 +/- 0.35 nA (n = 27) in approximately 80% of the neurones. 3. Histamine (10 microM) also blocked the post-spike slow after-hyperpolarization (AHP slow) present in 80% of these neurones (95 +/- 3.2%; n = 5). All neurones possessing AHPslow in ferret nodose were C fibre neurones; all AHPslow neurones had conduction velocities < or = 1 m s-1 (n = 7). 4. Both the histamine-induced inward current and the block of AHPslow were concentration dependent and each had an estimated EC50 value of 2 microM. These histamine-induced effects were mimicked by the histamine H1 receptor agonist 2-(2-aminoethyl) thiazole dihydrochloride (10 microM) and blocked by the H1 antagonists pyrilamine (100 nM) or diphenhydramine (100 nM). Schild plot analysis of the effect of pyrilamine on the histamine-induced inward current revealed a pA2 value of 9.7, consistent with that expected for an H1 receptor. Neither impromidine (10 microM) nor R(-)-alpha-methylhistamine (10 microM), selective H2 or H3 agonists, respectively, significantly affected the membrane potential, input resistance or AHPslow. 5. The reversal potential (Vrev) for the histamine-induced inward current was -84 +/- 2.1 mV (n = 4). The Vrev for the histamine response shifted in a Nernstian manner with changes in the extracellular potassium concentration. Alterations in the extracellular chloride concentration had no significant effect on the Vrev of the histamine response (n = 3). The Vrev for the AHPslow was -85 +/- 1.7 mV (n = 4). 6. These results indicate that histamine increases the excitability of ferret vagal afferent somata by interfering with two classes of

  13. Potassium and Health123

    PubMed Central

    Weaver, Connie M.

    2013-01-01

    Potassium was identified as a shortfall nutrient by the Dietary Guidelines for Americans 2010 Advisory Committee. The committee concluded that there was a moderate body of evidence of the association between potassium intake and blood pressure reduction in adults, which in turn influences the risk of stroke and coronary heart disease. Evidence is also accumulating of the protective effect of adequate dietary potassium on age-related bone loss and reduction of kidney stones. These benefits depend on organic anions associated with potassium as occurs in foods such as fruits and vegetables, in contrast to similar blood pressure-lowering benefits of potassium chloride. Benefits to blood pressure and bone health may occur at levels below current recommendations for potassium intake, especially from diet, but dose-response trials are needed to confirm this. Nevertheless, intakes considerably above current levels are needed for optimal health, and studies evaluating small increases in fruit and vegetable intake on bone and heart outcomes for short periods have had disappointing results. In modern societies, Western diets have led to a decrease in potassium intake with reduced consumption of fruits and vegetables with a concomitant increase in sodium consumption through increased consumption of processed foods. Consumption of white vegetables is associated with decreased risk of stroke, possibly related to their high potassium content. Potatoes are the highest source of dietary potassium, but the addition of salt should be limited. Low potassium-to-sodium intake ratios are more strongly related to cardiovascular disease risk than either nutrient alone. This relationship deserves further attention for multiple target tissue endpoints. PMID:23674806

  14. Potassium and health.

    PubMed

    Weaver, Connie M

    2013-05-01

    Potassium was identified as a shortfall nutrient by the Dietary Guidelines for Americans 2010 Advisory Committee. The committee concluded that there was a moderate body of evidence of the association between potassium intake and blood pressure reduction in adults, which in turn influences the risk of stroke and coronary heart disease. Evidence is also accumulating of the protective effect of adequate dietary potassium on age-related bone loss and reduction of kidney stones. These benefits depend on organic anions associated with potassium as occurs in foods such as fruits and vegetables, in contrast to similar blood pressure-lowering benefits of potassium chloride. Benefits to blood pressure and bone health may occur at levels below current recommendations for potassium intake, especially from diet, but dose-response trials are needed to confirm this. Nevertheless, intakes considerably above current levels are needed for optimal health, and studies evaluating small increases in fruit and vegetable intake on bone and heart outcomes for short periods have had disappointing results. In modern societies, Western diets have led to a decrease in potassium intake with reduced consumption of fruits and vegetables with a concomitant increase in sodium consumption through increased consumption of processed foods. Consumption of white vegetables is associated with decreased risk of stroke, possibly related to their high potassium content. Potatoes are the highest source of dietary potassium, but the addition of salt should be limited. Low potassium-to-sodium intake ratios are more strongly related to cardiovascular disease risk than either nutrient alone. This relationship deserves further attention for multiple target tissue endpoints.

  15. Potassium iodide (KI) to block the thyroid from exposure to I-131: current questions and answers to be discussed.

    PubMed

    Reiners, Christoph; Schneider, Rita

    2013-05-01

    Thyroid cancer in children and adolescents has to be considered as the most severe health consequence of a nuclear reactor emergency with release of radioiodine into the atmosphere. High doses of potassium iodide are effective to block radioiodine thyroid uptake and to prevent development of thyroid cancer years later. However, there are controversies concerning thyroid cancer risk induced by radioiodine exposure in adults. Further, the interaction of nutritional supply of potassium iodide and radioiodine uptake as well as the interaction of radioiodine with certain drugs has not been addressed properly in existing guidelines and recommendations. How to proceed in case of repeated release of radioiodine is an open, very important question which came up again recently during the Fukushima accident. Lastly, the side effects of iodine thyroid blocking and alternatives of this procedure have not been addressed systematically up to now in guidelines and recommendations. These questions can be answered as follows: in adults, the risk to develop thyroid cancer is negligible. In countries, where nutritional iodine deficiency is still an issue, the risk to develop thyroid cancer after a nuclear reactor emergency has to be considered higher because the thyroid takes up more radioiodine as in the replete condition. Similarly, in patients suffering from thyrotoxicosis, hypothyroidism or endemic goitre not being adequately treated radioiodine uptake is higher than in healthy people. In case of repeated or continued radioiodine release, more than one dose of potassium iodide may be necessary and be taken up to 1 week. Repeated iodine thyroid blocking obviously is not harmful. Side effects of iodine thyroid blocking should not be overestimated; there is little evidence for adverse effects in adults. Newborns and babies, however, may be more sensitive to side effects. In the rare case of iodine hypersensitivity, potassium perchlorate may be applied as an alternative to iodine for

  16. Potassium physiology.

    PubMed

    Thier, S O

    1986-04-25

    Potassium is the most abundant exchangeable cation in the body. It exists predominantly in the intracellular fluid at concentrations of 140 to 150 meq/liter and in the extracellular fluid at concentrations of 3.5 to 5 meq/liter. The maintenance of the serum potassium concentration is a complex bodily function and results from the balance between intake, excretion, and distribution between intracellular and extracellular space. Ingested potassium is virtually completely absorbed from and minimally excreted through the intestine under nonpathologic circumstances. Renal excretion of potassium, which is the major chronic protective mechanism against abnormalities in potassium balance, depends on filtration, reabsorption, and a highly regulated distal nephron secretory process. Factors regulating potassium secretion include prior potassium intake, intracellular potassium, delivery of sodium chloride and poorly reabsorbable anions to the distal nephron, the urine flow rate, hormones such as aldosterone and beta-catecholamines, and the integrity of the renal tubular cell. The maintenance of distribution between the inside and outside of cells depends on the integrity of the cell membrane and its pumps, osmolality, pH, and the hormones insulin, aldosterone, beta 2-catecholamines, alpha-catecholamines, and prostaglandins. Both distribution across cell membranes and/or renal excretion of potassium may be altered by pharmacologic agents such as diuretics, alpha- and beta-catechol antagonists and agonists, depolarizing agents, and digitalis. Problems with hypokalemia and hyperkalemia can be analyzed on the basis of potassium physiology and pharmacology; proper treatment depends on an accurate analysis.

  17. The Amplitude and Inactivation Properties of the Delayed Potassium Currents Are Regulated by Protein Kinase Activity in Hair Cells of the Frog Semicircular Canals

    PubMed Central

    Martini, Marta; Canella, Rita; Fesce, Riccardo; Rossi, Maria Lisa

    2013-01-01

    In hair cells dissected from the frog crista ampullaris, the combination of a calcium-dependent (IKCa) and a purely voltage-dependent component (IKV) gives rise to the delayed potassium current complex (IKD). These currents have been recently reported to display slow depolarization-induced inactivation and biphasic inactivation removal by hyperpolarization. The amplitude and inactivation kinetics of both IKCa and IKV are drastically modulated by a previously unrecognized mechanism of protein phosphorylation (sensitive to kinase inhibitors H89 and KT5823), which does not interfere with the transient potassium current (IA) or the calcium current (ICa). IKD amplitude was stable in cells patched with pipettes containing 8 mM ATP or under perforated-patch; under these conditions, a 10 min treatment with 10 µM H89 or 1–10 µM KT5823 reduced IKD amplitude by a mean of 67% at +40 mV. Similarly affected was the isolated IKV component (ICa blocked with Cd2+). Thus, a large potassium conductance can be activated by depolarization, but it is made available to the cell to a variable extent that depends on membrane potential and protein kinase activity. The total gKD ranged 4.6–44.0 nS in control cells, according to the level of steady-state inactivation, and was reduced to 1.4–2.7 nS after protein kinase inhibition. When sinusoidal membrane potential changes in the −70/−10 mV range were applied, to mimic receptor response to hair bundle deflection, IKD proved the main current dynamically activated and the only one regulated by PK: H89 decreased the total outward charge during each cycle by 60%. Phosphorylation appears to control both the amount of IKCa and IKV conductance activated by depolarization and the fraction thereof which can be rescued by removal of inactivation. The balance between the depolarizing transduction current and the repolarizing potassium current, and eventually the transmitter release at the cytoneural junction, are therefore modulated by a

  18. Genistein inhibition of OGD-induced brain neuron death correlates with its modulation of apoptosis, voltage-gated potassium and sodium currents and glutamate signal pathway.

    PubMed

    Ma, Xue-Ling; Zhang, Feng; Wang, Yu-Xiang; He, Cong-Cong; Tian, Kun; Wang, Hong-Gang; An, Di; Heng, Bin; Liu, Yan-Qiang

    2016-07-25

    In the present study, we established an in vitro model of hypoxic-ischemia via exposing primary neurons of newborn rats to oxygen-glucose deprivation (OGD) and observing the effects of genistein, a soybean isoflavone, on hypoxic-ischemic neuron viability, apoptosis, voltage-activated potassium (Kv) and sodium (Nav) currents, and glutamate receptor subunits. The results indicated that OGD exposure reduced the viability and increased the apoptosis of brain neurons. Meanwhile, OGD exposure caused changes in the current-voltage curves and current amplitude values of voltage-activated potassium and sodium currents; OGD exposure also decreased GluR2 expression and increased NR2 expression. However, genistein at least partially reversed the effects caused by OGD. The results suggest that hypoxic-ischemia-caused neuronal apoptosis/death is related to an increase in K(+) efflux, a decrease in Na(+) influx, a down-regulation of GluR2, and an up-regulation of NR2. Genistein may exert some neuroprotective effects via the modulation of Kv and Nav currents and the glutamate signal pathway, mediated by GluR2 and NR2. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. 21 CFR 184.1622 - Potassium chloride.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Potassium chloride. 184.1622 Section 184.1622 Food... Specific Substances Affirmed as GRAS § 184.1622 Potassium chloride. (a) Potassium chloride (KCl, CAS Reg... levels not to exceed current good manufacturing practice. Potassium chloride may be used in infant...

  20. 21 CFR 184.1622 - Potassium chloride.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Potassium chloride. 184.1622 Section 184.1622 Food... Specific Substances Affirmed as GRAS § 184.1622 Potassium chloride. (a) Potassium chloride (KCl, CAS Reg... levels not to exceed current good manufacturing practice. Potassium chloride may be used in infant...

  1. 21 CFR 184.1622 - Potassium chloride.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Potassium chloride. 184.1622 Section 184.1622 Food... Specific Substances Affirmed as GRAS § 184.1622 Potassium chloride. (a) Potassium chloride (KCl, CAS Reg... levels not to exceed current good manufacturing practice. Potassium chloride may be used in infant...

  2. 21 CFR 184.1622 - Potassium chloride.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Potassium chloride. 184.1622 Section 184.1622 Food... Specific Substances Affirmed as GRAS § 184.1622 Potassium chloride. (a) Potassium chloride (KCl, CAS Reg... levels not to exceed current good manufacturing practice. Potassium chloride may be used in infant...

  3. Action of niflumic acid on evoked and spontaneous calcium-activated chloride and potassium currents in smooth muscle cells from rabbit portal vein.

    PubMed

    Hogg, R C; Wang, Q; Large, W A

    1994-07-01

    1. The action of niflumic acid was studied on spontaneous and evoked calcium-activated chloride (ICl(Ca)) and potassium (IK(Ca)) currents in rabbit isolated portal vein cells. 2. With the nystatin perforated patch technique in potassium-containing solutions at a holding potential of -77 mV (the potassium equilibrium potential), niflumic acid produced a concentration-dependent inhibition of spontaneous transient inward current (STIC, calcium-activated chloride current) amplitude. The concentration to reduce the STIC amplitude by 50% (IC50) was 3.6 x 10(-6) M. 3. At -77 mV holding potential, niflumic acid converted the STIC decay from a single exponential to 2 exponential components. In niflumic acid the fast component of decay was faster, and the slow component was slower than the control decay time constant. Increasing the concentration of niflumic acid enhanced the decay rate of the fast component and reduced the decay rate of the slow component. 4. The effect of niflumic acid on STIC amplitude was voltage-dependent and at -50 and +50 mV the IC50 values were 2.3 x 10(-6) M and 1.1 x 10(-6) M respectively (cf. 3.6 x 10(-6) M at -77 mV). 5. In K-free solutions at potentials of -50 mV and +50 mV, niflumic acid did not induce a dual exponential STIC decay but just increased the decay time constant at both potentials in a concentration-dependent manner. 6. Niflumic acid, in concentrations up to 5 x 10(-5) M, had no effect on spontaneous calcium-activated potassium currents. 7. Niflumic acid inhibited noradrenaline- and caffeine-evoked IO(Ca) with an ICM50 of 6.6 x 10-6 M, i.e.was less potent against evoked currents compared to spontaneous currents. In contrast niflumic acid(2 x 10-6 M-5 x 105 M) increased noradrenaline- and caffeine-induced IK(ca).8. The results are discussed with respect to the mechanism of block of ICl(Ca) by niflumic acid and its suitability as a pharmacological tool for assessing the role of Ic(ca) in physiological mechanisms.

  4. Dopamine modulates two potassium currents and inhibits the intrinsic firing properties of an identified motor neuron in a central pattern generator network.

    PubMed

    Kloppenburg, P; Levini, R M; Harris-Warrick, R M

    1999-01-01

    The two pyloric dilator (PD) neurons are components [along with the anterior burster (AB) neuron] of the pacemaker group of the pyloric network in the stomatogastric ganglion of the spiny lobster Panulirus interruptus. Dopamine (DA) modifies the motor pattern generated by the pyloric network, in part by exciting or inhibiting different neurons. DA inhibits the PD neuron by hyperpolarizing it and reducing its rate of firing action potentials, which leads to a phase delay of PD relative to the electrically coupled AB and a reduction in the pyloric cycle frequency. In synaptically isolated PD neurons, DA slows the rate of recovery to spike after hyperpolarization. The latency from a hyperpolarizing prestep to the first action potential is increased, and the action potential frequency as well as the total number of action potentials are decreased. When a brief (1 s) puff of DA is applied to a synaptically isolated, voltage-clamped PD neuron, a small voltage-dependent outward current is evoked, accompanied by an increase in membrane conductance. These responses are occluded by the combined presence of the potassium channel blockers 4-aminopyridine and tetraethylammonium. In voltage-clamped PD neurons, DA enhances the maximal conductance of a voltage-sensitive transient potassium current (IA) and shifts its Vact to more negative potentials without affecting its Vinact. This enlarges the "window current" between the voltage activation and inactivation curves, increasing the tonically active IA near the resting potential and causing the cell to hyperpolarize. Thus DA's effect is to enhance both the transient and resting K+ currents by modulating the same channels. In addition, DA enhances the amplitude of a calcium-dependent potassium current (IO(Ca)), but has no effect on a sustained potassium current (IK(V)). These results suggest that DA hyperpolarizes and phase delays the activity of the PD neurons at least in part by modulating their intrinsic postinhibitory recovery

  5. A biophysical model examining the role of low-voltage-activated potassium currents in shaping the responses of vestibular ganglion neurons.

    PubMed

    Hight, Ariel E; Kalluri, Radha

    2016-08-01

    The vestibular nerve is characterized by two broad groups of neurons that differ in the timing of their interspike intervals; some fire at highly regular intervals, whereas others fire at highly irregular intervals. Heterogeneity in ion channel properties has been proposed as shaping these firing patterns (Highstein SM, Politoff AL. Brain Res 150: 182-187, 1978; Smith CE, Goldberg JM. Biol Cybern 54: 41-51, 1986). Kalluri et al. (J Neurophysiol 104: 2034-2051, 2010) proposed that regularity is controlled by the density of low-voltage-activated potassium currents (IKL). To examine the impact of IKL on spike timing regularity, we implemented a single-compartment model with three conductances known to be present in the vestibular ganglion: transient sodium (gNa), low-voltage-activated potassium (gKL), and high-voltage-activated potassium (gKH). Consistent with in vitro observations, removing gKL depolarized resting potential, increased input resistance and membrane time constant, and converted current step-evoked firing patterns from transient (1 spike at current onset) to sustained (many spikes). Modeled neurons were driven with a time-varying synaptic conductance that captured the random arrival times and amplitudes of glutamate-driven synaptic events. In the presence of gKL, spiking occurred only in response to large events with fast onsets. Models without gKL exhibited greater integration by responding to the superposition of rapidly arriving events. Three synaptic conductance were modeled, each with different kinetics to represent a variety of different synaptic processes. In response to all three types of synaptic conductance, models containing gKL produced spike trains with irregular interspike intervals. Only models lacking gKL when driven by rapidly arriving small excitatory postsynaptic currents were capable of generating regular spiking.

  6. Seasonal acclimatization of the cardiac potassium currents (IK1 and IKr) in an arctic marine teleost, the navaga cod (Eleginus navaga).

    PubMed

    Abramochkin, Denis V; Vornanen, Matti

    2015-12-01

    Several freshwater fishes of north-temperate latitudes exhibit marked seasonal changes in cardiac action potential (AP) waveform as an outcome of temperature-dependent changes in the density of delayed rectifiers (IKr, IKs) and inward rectifier (IK1) potassium currents. Thus far, ionic mechanisms of cardiac excitability in arctic marine fishes have not been examined. To this end we examined ventricular AP and the role of two major potassium currents (IK1, IKr) in repolarization of cardiac AP in winter-acclimatized (WA, caught in March) and summer-acclimatized (SA, caught in September) navaga cod (Eleginus navaga) of the White Sea. The duration of ventricular AP of WA navaga at 3 °C (APD50 = 659.5 ± 32.8 ms) was similar to the AP duration of SA navaga at 12 °C (APD50 = 543.9 ± 14.6 ms) (p > 0.05) indicating complete thermal compensation of AP duration. This acclimation effect was associated with strong up-regulation of the cardiac potassium currents in winter. Densities of ventricular IK1 (at -120 mV) and IKr (at +50 mV) of the WA navaga at 3 °C were 2.9 times and 2.8 times, respectively, higher than those of the SA navaga at 12 °C, thus indicating marked thermal overcompensation. Qualitatively similar results were obtained from atrial myocytes. Seasonal changes in IK1 and IKr are more than sufficient to explain the complete thermal compensation of ventricular AP duration. The excellent acclimation capacity of cardiac excitability of the navaga cod is probably needed to maintain high cardiac performance at subzero temperatures in winter and to increase thermal resilience of cardiac function under seasonally variable arctic temperature conditions.

  7. Properties of two voltage-activated potassium currents in acutely isolated juvenile rat dentate gyrus granule cells.

    PubMed

    Beck, H; Ficker, E; Heinemann, U

    1992-12-01

    1. The properties of outward currents were investigated in acutely isolated dentate gyrus granule cells at postnatal ages of day 5-7, 10-14, 18-24 (P5-7, P10-14, P18-24) and at adulthood (2-3 mo), with the use of the whole-cell patch-clamp technique. 2. Kinetic analysis and pharmacological properties showed that an A-type K+ current (IA) and a delayed rectifier current (IK) were present in these cells. 3. IA in P10-14 cells activated and inactivated rapidly with a decay time constant of 7.5 +/- 2.1 (SD) ms with command pulses to +30 mV. The removal of inactivation was monoexponential with a time constant of 23.1 ms (holding potential, -50 mV; conditioning voltage steps of varying duration to -110 mV). V 1/2 of the Boltzmann function describing steady-state inactivation was -65.1 +/- 1.8 mV with a slope factor of -6.0. IA was sensitive to 5 mM 4-aminopyridine (4-AP) but not to 10 mM tetraethylammonium (TEA). 4. IK in P10-14 cells displayed a voltage-dependent activation time constant (4.3 +/- 0.8 ms for command pulses to +30 mV and 16.2 +/- 2.4 for command pulses to -10 mV) and a double-exponential decay (time constants 194 +/- 21 and 1,625 +/- 254 ms). The rate constant of removal of inactivation was 332.1 ms. IK showed a reduction by 61.4 +/- 5.3% with 10 mM TEA and was partially blocked by 5 mM 4-AP in a subpopulation of cells. 5. Whereas IA remained stable over time, IK showed a substantial reduction of current amplitude by 67% after 30 min of cell perfusion through the patch pipette. The time course of this reduction was monoexponential with a time constant of 6.9 min and was partly due to a shift in V1/2 of the steady-state inactivation from -79.2 to -99.6 mV. 6. IA and IK remained stable with respect to kinetic properties during ontogenesis. However, the relative contribution and pharmacological properties of the investigated K+ currents varied with age. Although IA dominated in P5-7 cells, IK was prominent in most older cells. Five millimolars 4-AP reduced

  8. Does Hemodialysis Dialysate Potassium Composition Matter?.

    PubMed

    Haras, Mary S

    2015-01-01

    Dyskalemia is known to cause cardiac arrhythmias and cardiac arrest. In persons undergoing hemodialysis, potassium dialysate composition has been identified as a contributingfactor in addition to co-morbidities, medications, dietary potassium intake, and stage of kidney disease. Current evidence recommends a thorough evaluation of all factors affecting potassium balance, and lower potassium concentration should be used cautiously in patients who are likely to develop cardiac arrhythmias. Nephrology nurses play a key role inpatient assessment and edu- cation related to potassium balance.

  9. The activation of N-methyl-d-aspartate receptors downregulates transient outward potassium and L-type calcium currents in rat models of depression.

    PubMed

    Liu, Xin; Shi, Shaobo; Yang, Hongjie; Qu, Chuan; Chen, Yuting; Liang, Jinjun; Yang, Bo

    2017-08-01

    Major depression is an important clinical factor in ventricular arrhythmia. Patients diagnosed with major depression overexpress N-methyl-d-aspartate receptors (NMDARs). Previous studies found that chronic NMDAR activation increases susceptibility to ventricular arrhythmias. We aimed to explore the mechanisms by which NMDAR activation may increase susceptibility to ventricular arrhythmias. Male rats were randomly assigned to either normal environments as control (CTL) group or 4 wk of chronic mild stress (CMS) to produce a major depression disorder (MDD) model group. After 4 wk of CMS, depression-like behaviors were measured in both groups. Varying doses (1-100 μM) of NMDA and 10 μM NMDA antagonist (MK-801) were perfused through ventricular myocytes isolated from MDD rats to measure the L-type calcium current (ICa-L) and transient outward potassium current (Ito). Structural remodeling was assessed using serial histopathology including Masson's trichrome dye. Electrophysiological characteristics were evaluated using Langendorff perfusion. Depression-like behaviors were observed in MDD rats. MDD rats showed longer action potential durations at 90% repolarization and higher susceptibility to ventricular arrhythmias than CTL rats. MDD rats showed lower ICa-L and Ito current densities than CTL rats. Additionally, NMDA reduced both currents in a concentration-dependent manner, whereas there was no significant impact on the currents when perfused with MK-801. MDD rats exhibited significantly more fibrosis areas in heart tissue and reduced expression of Kv4.2, Kv4.3, and Cav1.2. We observed that acute NMDAR activation led to downregulation of potassium and L-type calcium currents in a rat model of depression, which may be the mechanism underlying ventricular arrhythmia promotion by depression. Copyright © 2017 the American Physiological Society.

  10. Lithium, Sodium, and Potassium Abundances in Sharp-Lined A-Type Stars Takeda, Yoichi; Kang, Dong-Il; Han, Inwoo; Lee, Byeong-Cheol; Kim, Kang-Min; Kawanomoto, Satoshi; Ohishi, Naoko;

    NASA Astrophysics Data System (ADS)

    2012-04-01

    The abundances of alkali elements (Li, Na, and K) were determined from the Li I 6708, Na I 5682/5688, and K I 7699 lines by taking into account the non-LTE effect for 24 sharp-lined A-type stars (ve sin i ≲ 50 km s-1, 7000 K &lesssim Teff &lessim 10000 K, many showing Am peculiarities to different degrees), based on high-dispersion and high-S/N spectral data secured at BOAO (Korea) and OAO (Japan). We found a significant trend that A(Na) tightly scales with A(Fe) irrespective of Teff, which means that Na becomes enriched similarly to Fe in accordance with the degree of Am peculiarity. Regarding lithium, A(Li) mostly ranges between ˜ 3 and ˜ 3.5 (i.e., almost the same as or slightly less than the solar system abundance of 3.3) with a weak decreasing tendency with a lowering of Teff at Teff &lesssim 8000 K, though several stars exceptionally show distinctly larger depletion. The abundances of potassium also revealed an apparent Teff-dependence in the sense that A(K) in late-A stars tends to be mildly subsolar [possibly with a weak anti-correlation with A(Fe)] systematically decreasing from ˜ 5.0 (Teff ˜ 8500 K) to ˜ 4.6 (Teff ˜ 7500 K), while those for early-A stars remain near-solar around ˜ 5.0-5.2. These observational facts may serve as important constraints for any theory aiming to explain chemical anomalies of A-type stars.

  11. 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 (IA) decreased in the coculture system, whereas the outward delayed-rectifier potassium currents (IK) did not. Sodium nitroprusside, a NO donor, enhanced BMEC-induced IA 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 IA. These results indicate that vascular endothelial cells assist neurons to prevent hypoxic injury via inhibiting neuronal IA 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.

  12. Regulation of KChIP2 potassium channel beta subunit gene expression underlies the gradient of transient outward current in canine and human ventricle.

    PubMed

    Rosati, B; Pan, Z; Lypen, S; Wang, H S; Cohen, I; Dixon, J E; McKinnon, D

    2001-05-15

    Expression of four members of the KChIP family of potassium channel beta subunits was examined in canine heart. Only one member of the gene family, KChIP2, was expressed in heart. There was a steep gradient of KChIP2 mRNA expression across the canine ventricular free wall. KChIP2 mRNA was 25-fold more abundant in the epicardium than in the endocardium, and this gradient paralleled the gradient in transient outward current (Ito) expression. In contrast, Kv4.3 potassium channel alpha subunit mRNA was expressed at equal levels across the ventricular wall. There was no difference in the pharmacological sensitivity of epicardial and endocardial Ito channels to flecainide, suggesting that the current is produced by the same channel in the two tissues. A similar gradient of KChIP2 expression was found across the ventricular wall of human heart, but not rat heart. It is concluded that transcriptional regulation of the KChIP2 beta subunit gene, rather than the Kv4.3 [alpha] subunit gene, is the primary determinant regulating the transmural gradient of Ito expression in the ventricular free wall of canine and human heart.

  13. Differential expression of K4-AP currents and Kv3.1 potassium channel transcripts in cortical neurons that develop distinct firing phenotypes.

    PubMed

    Massengill, J L; Smith, M A; Son, D I; O'Dowd, D K

    1997-05-01

    Maturation of electrical excitability during early postnatal development is critical to formation of functional neural circuitry in the mammalian neocortex. Little is known, however, about the changes in gene expression underlying the development of firing properties that characterize different classes of cortical neurons. Here we describe the development of cortical neurons with two distinct firing phenotypes, regular-spiking (RS) and fast-spiking (FS), that appear to emerge from a population of immature multiple-spiking (IMS) neurons during the first two postnatal weeks, both in vivo (within layer IV) and in vitro. We report the expression of a slowly inactivating, 4-AP-sensitive potassium current (K4-AP) at significantly higher density in FS compared with RS neurons. The same current is expressed at intermediate levels in IMS neurons. The kinetic, voltage-dependent, and pharmacological properties of the K4-AP current are similar to those observed by heterologous expression of Kv3.1 potassium channel mRNA. Single-cell RT-PCR analysis demonstrates that PCR products representing Kv3.1 transcripts are amplified more frequently from FS than RS neurons, with an intermediate frequency of Kv3.1 detection in neurons with immature firing properties. Taken together, these data suggest that the Kv3.1 gene encodes the K4-AP current and that expression of this gene is regulated in a cell-specific manner during development. Analysis of the effects of 4-AP on firing properties suggests that the K4-AP current is important for rapid action potential repolarization, fast after-hyperpolarization, brief refractory period, and high firing frequency characteristic of FS GABAergic interneurons.

  14. Potassium Iodide

    MedlinePlus

    ... radioactive iodine that may be released during a nuclear radiation emergency. Radioactive iodine can damage the thyroid gland. ... only take potassium iodide if there is a nuclear radiation emergency and public officials tell you that you ...

  15. Voltage-gated potassium currents are targets of diurnal changes in estradiol feedback regulation and kisspeptin action on gonadotropin-releasing hormone neurons in mice.

    PubMed

    Pielecka-Fortuna, Justyna; DeFazio, R Anthony; Moenter, Suzanne M

    2011-11-01

    Estradiol has both negative and positive feedback actions upon gonadotropin-releasing hormone (GnRH) release; the latter actions trigger the preovulatory GnRH surge. Although neurobiological mechanisms of the transitions between feedback modes are becoming better understood, the roles of voltage-gated potassium currents, major contributors to neuronal excitability, are unknown. Estradiol alters two components of potassium currents in these cells: a transient current, I(A), and a sustained current, I(K). Kisspeptin is a potential mediator between estradiol and GnRH neurons and can act directly on GnRH neurons. We examined how estradiol, time of day, and kisspeptin interact to regulate these conductances in a mouse model exhibiting daily switches between estradiol negative (morning) and positive feedback (evening). Whole-cell voltage clamp recordings were made from GnRH neurons in brain slices from ovariectomized (OVX) mice and from OVX mice treated with estradiol (OVX+E). There were no diurnal changes in either I(A) or I(K) in GnRH neurons from OVX mice. In contrast, in GnRH neurons from OVX+E mice, I(A) and I(K) were greater during the morning when GnRH neuron activity is low and smaller in the evening when GnRH neuron activity is high. Estradiol increased I(A) in the morning and decreased it in the evening, relative to that in cells from OVX mice. Exogenously applied kisspeptin reduced I(A) regardless of time of day or estradiol status. Estradiol, interacting with time of day, and kisspeptin both depolarized I(A) activation. These findings extend our understanding of both the neurobiological mechanisms of estradiol negative vs. positive regulation of GnRH neurons and of kisspeptin action on these cells.

  16. Kv4 Channels Underlie the Subthreshold-Operating A-type K-current in Nociceptive Dorsal Root Ganglion Neurons.

    PubMed

    Phuket, Thanawath Ratanadilok Na; Covarrubias, Manuel

    2009-01-01

    The dorsal root ganglion (DRG) contains heterogeneous populations of sensory neurons including primary nociceptive neurons and C-fibers implicated in pain signaling. Recent studies have demonstrated DRG hyperexcitability associated with downregulation of A-type K(+) channels; however, the molecular correlate of the corresponding A-type K(+) current (I(A)) has remained hypothetical. Kv4 channels may underlie the I(A) in DRG neurons. We combined electrophysiology, molecular biology (Whole-Tissue and Single-Cell RT-PCR) and immunohistochemistry to investigate the molecular basis of the I(A) in acutely dissociated DRG neurons from 7- to 8-day-old rats. Whole-cell recordings demonstrate a robust tetraethylammonium-resistant (20 mM) and 4-aminopyridine-sensitive (5 mM) I(A). Matching Kv4 channel properties, activation and inactivation of this I(A) occur in the subthreshold range of membrane potentials and the rate of recovery from inactivation is rapid and voltage-dependent. Among Kv4 transcripts, the DRG expresses significant levels of Kv4.1 and Kv4.3 mRNAs. Also, single small-medium diameter DRG neurons ( approximately 30 mum) exhibit correlated frequent expression of mRNAs encoding Kv4.1 and Nav1.8, a known nociceptor marker. In contrast, the expressions of Kv1.4 and Kv4.2 mRNAs at the whole-tissue and single-cell levels are relatively low and infrequent. Kv4 protein expression in nociceptive DRG neurons was confirmed by immunohistochemistry, which demonstrates colocalization of Kv4.3 and Nav1.8, and negligible expression of Kv4.2. Furthermore, specific dominant-negative suppression and overexpression strategies confirmed the contribution of Kv4 channels to I(A) in DRG neurons. Contrasting the expression patterns of Kv4 channels in the central and peripheral nervous systems, we discuss possible functional roles of these channels in primary sensory neurons.

  17. Sodium metabisulfite modulation of potassium channels in pain-sensing dorsal root ganglion neurons.

    PubMed

    Nie, Aifang; Wei, Cailing; Meng, Ziqiang

    2009-12-01

    The effects of sodium metabisulfite (SMB), a general food preservative, on potassium currents in rat dorsal root ganglion (DRG) neurons were investigated using the whole-cell patch-clamp technique. SMB increased the amplitudes of both transient outward potassium currents and delayed rectifier potassium current in concentration- and voltage-dependent manner. The transient outward potassium currents (TOCs) include a fast inactivating (A-current or IA) current and a slow inactivating (D-current or ID) current. SMB majorly increased IA, and ID was little affected. SMB did not affect the activation process of transient outward currents (TOCs), but the inactivation curve of TOCs was shifted to more positive potentials. The inactivation time constants of TOCs were also increased by SMB. For delayed rectifier potassium current (IK), SMB shifted the activation curve to hyperpolarizing direction. SMB differently affected TOCs and IK, its effects major on A-type K+ channels, which play a role in adjusting pain sensitivity in response to peripheral redox conditions. SMB did not increase TOCs and IK when adding DTT in pipette solution. These results suggested that SMB might oxidize potassium channels, which relate to adjusting pain sensitivity in pain-sensing DRG neurons.

  18. A major role for calcium-dependent potassium current in action potential repolarization in adrenal chromaffin cells.

    PubMed

    Pancrazio, J J; Johnson, P A; Lynch, C

    1994-12-30

    To determine the extent which Ca dependent K current (IKCa) contributes during an action potential (AP), bovine chromaffin cells were voltage-clamped using a pre-recorded AP as the command voltage waveform. Based on (1) differential sensitivity of IKCa and Ca-independent K current (IK) to tetraethylammonium; (2) measurements of AP currents under conditions where Ca activation of IKCa had been abolished; and (3) blockade by charybdotoxin, IKCa comprised 70-90% of the outward K current during AP repolarization. In addition, observations are made concerning the form of AP-evoked Ca current.

  19. Dendritic potassium channels in hippocampal pyramidal neurons

    PubMed Central

    Johnston, Daniel; Hoffman, Dax A; Magee, Jeffrey C; Poolos, Nicholas P; Watanabe, Shigeo; Colbert, Costa M; Migliore, Michele

    2000-01-01

    Potassium channels located in the dendrites of hippocampal CA1 pyramidal neurons control the shape and amplitude of back-propagating action potentials, the amplitude of excitatory postsynaptic potentials and dendritic excitability. Non-uniform gradients in the distribution of potassium channels in the dendrites make the dendritic electrical properties markedly different from those found in the soma. For example, the influence of a fast, calcium-dependent potassium current on action potential repolarization is progressively reduced in the first 150 μm of the apical dendrites, so that action potentials recorded farther than 200 μm from the soma have no fast after-hyperpolarization and are wider than those in the soma. The peak amplitude of back-propagating action potentials is also progressively reduced in the dendrites because of the increasing density of a transient potassium channel with distance from the soma. The activation of this channel can be reduced by the activity of a number of protein kinases as well as by prior depolarization. The depolarization from excitatory postsynaptic potentials (EPSPs) can inactivate these A-type K+ channels and thus lead to an increase in the amplitude of dendritic action potentials, provided the EPSP and the action potentials occur within the appropriate time window. This time window could be in the order of 15 ms and may play a role in long-term potentiation induced by pairing EPSPs and back-propagating action potentials. PMID:10811726

  20. Dendritic potassium channels in hippocampal pyramidal neurons.

    PubMed

    Johnston, D; Hoffman, D A; Magee, J C; Poolos, N P; Watanabe, S; Colbert, C M; Migliore, M

    2000-05-15

    Potassium channels located in the dendrites of hippocampal CA1 pyramidal neurons control the shape and amplitude of back-propagating action potentials, the amplitude of excitatory postsynaptic potentials and dendritic excitability. Non-uniform gradients in the distribution of potassium channels in the dendrites make the dendritic electrical properties markedly different from those found in the soma. For example, the influence of a fast, calcium-dependent potassium current on action potential repolarization is progressively reduced in the first 150 micrometer of the apical dendrites, so that action potentials recorded farther than 200 micrometer from the soma have no fast after-hyperpolarization and are wider than those in the soma. The peak amplitude of back-propagating action potentials is also progressively reduced in the dendrites because of the increasing density of a transient potassium channel with distance from the soma. The activation of this channel can be reduced by the activity of a number of protein kinases as well as by prior depolarization. The depolarization from excitatory postsynaptic potentials (EPSPs) can inactivate these A-type K+ channels and thus lead to an increase in the amplitude of dendritic action potentials, provided the EPSP and the action potentials occur within the appropriate time window. This time window could be in the order of 15 ms and may play a role in long-term potentiation induced by pairing EPSPs and back-propagating action potentials.

  1. Potassium currents induced by hydrostatic pressure modulate membrane potential and transmitter release in vestibular type II hair cells.

    PubMed

    Duong Dinh, Thien An; Haasler, Thorsten; Homann, Georg; Jüngling, Eberhard; Westhofen, Martin; Lückhoff, Andreas

    2009-06-01

    Vestibular type II hair cells respond to increases in the hydrostatic pressure with pressure-dependent K(+) currents. We examined whether such currents may modulate transmitter release (assessed as membrane capacitance increments) by altering membrane potentials and voltage-gated Ca(2+) currents. Capacitance increments were dependent on voltage-gated Ca(2+) influx. Stimulating currents (0.7 nA) in current clamp induced depolarisations that were more negative by 8.7 +/- 2.1 mV when the bath height was elevated from 0.2 to 0.5 cm. In voltage clamp, protocols were used that simulated the time course of the membrane potential in current clamp at either low (control) or high hydrostatic pressure (high bath). The low bath protocol induced significantly larger Ca(2+) currents and increases in capacitance than the high bath protocol. We conclude that pressure-dependent K(+) currents may alter the voltage response of vestibular hair cells to an extent critical for Ca(2+) currents and transmitter release. This mechanism may contribute to vestibular dysfunction in Meniere's disease.

  2. High-threshold, Kv3-like potassium currents in magnocellular neurosecretory neurons and their role in spike repolarization.

    PubMed

    Shevchenko, Talent; Teruyama, Ryoichi; Armstrong, William E

    2004-11-01

    We identified Kv3-like high-threshold K+ currents in hypothalamic supraoptic neurons using whole cell recordings in hypothalamic slices and in acutely dissociated neurons. Tetraethylammonium (TEA)-sensitive currents (< 1 mM TEA) evoked from -50 mV were characterized by a large component that inactivated in 10-30 ms, and a smaller, persistent component that inactivated in 1-2 s. I/V relations in dissociated neurons revealed TEA-subtracted currents with a slope and voltage dependency consistent with the presence of Kv3-like channels. In slices, tests with 0.01-0.7 mM TEA produced an IC50 of 200-300 nM for both fast and persistent currents. The fast transient current was similar to currents associated with the expression of Kv3.4 subunits, given that it was sensitive to BDS-I (100 nM). The persistent TEA-sensitive current appeared similar to those attributed to Kv3.1/3.2 subunits. Although qualitatively similar, oxytocin (OT) and vasopressin (VP) neurons in slices differed in the stronger presence of persistent current in VP neurons. In both cell types, the IC50 for TEA-induced spike broadening was similar to that observed for current suppression in voltage clamp. However, TEA had a greater effect on the spike width of VP neurons than of OT neurons. Immunochemical studies revealed a stronger expression of the Kv3.1b alpha-subunit in VP neurons, which may be related to the greater importance of this current type in VP spike repolarization. Because OT and VP neurons are not considered fast firing, but do exhibit frequency- and calcium-dependent spike broadening, Kv3-like currents may be important for maintaining spike width and calcium influx within acceptable limits during repetitive firing.

  3. A whole-cell and single-channel study of the voltage-dependent outward potassium current in avian hepatocytes

    PubMed Central

    1988-01-01

    Voltage-dependent membrane currents were studied in dissociated hepatocytes from chick, using the patch-clamp technique. All cells had voltage-dependent outward K+ currents; in 10% of the cells, a fast, transient, tetrodotoxin-sensitive Na+ current was identified. None of the cells had voltage-dependent inward Ca2+ currents. The K+ current activated at a membrane potential of about -10 mV, had a sigmoidal time course, and did not inactivate in 500 ms. The maximum outward conductance was 6.6 +/- 2.4 nS in 18 cells. The reversal potential, estimated from tail current measurements, shifted by 50 mV per 10-fold increase in the external K+ concentration. The current traces were fitted by n2 kinetics with voltage-dependent time constants. Omitting Ca2+ from the external bath or buffering the internal Ca2+ with EGTA did not alter the outward current, which shows that Ca2+-activated K+ currents were not present. 1-5 mM 4-aminopyridine, 0.5-2 mM BaCl2, and 0.1-1 mM CdCl2 reversibly inhibited the current. The block caused by Ba was voltage dependent. Single-channel currents were recorded in cell- attached and outside-out patches. The mean unitary conductance was 7 pS, and the channels displayed bursting kinetics. Thus, avian hepatocytes have a single type of K+ channel belonging to the delayed rectifier class of K+ channels. PMID:2453605

  4. Pharmacological modulation of transmitter release by inhibition of pressure-dependent potassium currents in vestibular hair cells.

    PubMed

    Haasler, Thorsten; Homann, Georg; Duong Dinh, Thien An; Jüngling, Eberhard; Westhofen, Martin; Lückhoff, Andreas

    2009-12-01

    Vestibular vertigo may be induced by increases in the endolymphatic pressure that activate pressure-dependent K(+) currents (I(K,p)) in vestibular hair cells. I(K,p) have been demonstrated to modulate transmitter release and are inhibited by low concentrations of cinnarizine. Beneficial effects against vestibular vertigo of cinnarizine have been attributed to its inhibition of calcium currents. Our aim was to determine the extent by which the inhibition of I(K,p) by cinnarizine may alter the voltage response to stimulating currents and to analyze whether such alterations may be sufficient to modulate the activation of Ca(2+) currents and transmitter release. Vestibular type II hair cells from guinea pigs were studied using the whole-cell patch-clamp technique. In current clamp, voltage responses to trains of stimulating currents were recorded. In voltage clamp, transmitter release was assessed from changes in the cell capacitance, as calculated from the phase shift during application of sine waves. Cinnarizine (0.05-3 microM) concentration dependently reversed the depressing effects of increases in the hydrostatic pressure (from 0.2 to 0.5 cm H(2)O) on the voltage responses to stimulating currents. Voltage protocols that simulated these responses were applied in voltage clamp and revealed a significantly enhanced transmitter release in conditions mimicking an inhibition of I(K,p). Cinnarizine (< or =0.5 microM) did not inhibit calcium currents. We conclude that cinnarizine, in pharmacologically relevant concentrations, enhances transmitter release in the presence of elevated hydrostatic pressure by an indirect mechanism, involving inhibition of I(K,p), enhancing depolarization, and increasing the voltage-dependent activation of Ca(2+) currents, without directly affecting Ca(2+) current.

  5. After effects of perfusion with glucose-insulin-potassium solution on the membrane current and tension components of frog atrial muscle.

    PubMed

    Kinoshita, K; Yatani, A

    1982-09-01

    As glucose-insulin-potassium solution (GIK) has been used as clinical cardioplegia during open heart surgery, we studied the fundamental effects of GIK on the electrical and mechanical activities of the bullfrog atrial muscle under voltage clamped and unclamped conditions by the double sucrose-gap method. GIK produced an immediate disappearance of the action potential and twitch tension with pronounced depolarization accompanied by transient contracture. Reperfusion with normal Ringer's solution after GIK perfusion (30-180 min) resulted in recovery of the action potential, with an initial lengthening followed by a sustained shortening in duration. Recovery of twitch tension was incomplete, and perfusion with GIK for a longer period caused stronger suppression. Voltage clamp studies revealed that after removal of GIK, the slow inward current (Is) and Is-dependent tension were markedly depressed, while the delayed outward current (Ix) was augmented. The fast inward current (INaf), background current (Ik1), and Is-independent tension gradually recovered to the control levels. Perfusion with low Ca Ringer's solution or verapamil Ringer's solution for 10 min at the initial reperfusion phase significantly improved the recovery of Is and the Is-dependent tension. These results indicate that the after-effects of GIK are mainly governed by Ca influx at the initial reperfusion phase. Therefore, a lowering of the Ca influx in this period is expected to produce a beneficial effect on cardiac function after GIK treatment.

  6. Voltage‐dependent potassium currents expressed in Xenopus laevis oocytes after injection of mRNA isolated from trophozoites of Giardia lamblia (strain Portland‐1)

    PubMed Central

    Ponce, Arturo; Jimenez‐Cardoso, Enedina; Eligio‐Garcia, Leticia

    2013-01-01

    Abstract Despite its importance as a health problem issue, almost nothing is known about the membrane physiology of Giardia lamblia and practically there exist no information so far regarding the variety and properties of ion channels that this protozoan parasite possesses. To address this subject we resorted to an indirect method, consisting in the injection of mRNA and further characterization of ion currents in Xenopus oocytes. In this work, we show that oocytes injected with mRNA isolated from cultured trophozoites of G. lamblia, strain Portland‐1 express novel potassium currents that appear over the second day after injection and show time‐ and voltage‐dependent activation followed by a slow inactivation. They start activating at −90 mV, with V1/2 of −30 mV; its time constant of activation (at +60 mV) is 0.11 sec, whereas that of inactivation is 1.92 sec, V1/2 = −44.6 mV. Such K currents were effectively blocked by K channel blockers TEA and 4AP, as well as Ba2+, quinine, quinidine, charybdotoxin, dendrotoxin‐1, capsaicin, margatoxin, and diltiazem. These results suggest that such currents are the result of expression of Giardia′s voltage‐gated K channels heterologously expressed in Xenopus laevis oocytes. PMID:24744864

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

    PubMed

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

    2017-09-01

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

  8. Regulation of renal potassium secretion: molecular mechanisms.

    PubMed

    Welling, Paul A

    2013-05-01

    A new understanding of renal potassium balance has emerged as the molecular underpinnings of potassium secretion have become illuminated, highlighting the key roles of apical potassium channels, renal outer medullary potassium channel (ROMK) and Big Potassium (BK), in the aldosterone-sensitive distal nephron and collecting duct. These channels act as the final-regulated components of the renal potassium secretory machinery. Their activity, number, and driving forces are precisely modulated to ensure potassium excretion matches dietary potassium intake. Recent identification of the underlying regulatory mechanisms at the molecular level provides a new appreciation of the physiology and reveals a molecular insight to explain the paradoxic actions of aldosterone on potassium secretion. Here, we review the current state of knowledge in the field.

  9. KChIP1 modulation of Kv4.3-mediated A-type K(+) currents and repetitive firing in hippocampal interneurons.

    PubMed

    Bourdeau, M L; Laplante, I; Laurent, C E; Lacaille, J-C

    2011-03-10

    Neuronal A-type K(+) channels regulate action potential waveform, back-propagation and firing frequency. In hippocampal CA1 interneurons located at the stratum lacunosum-moleculare/radiatum junction (LM/RAD), Kv4.3 mediates A-type K(+) currents and a Kv4 β-subunit of the Kv channel interacting protein (KChIP) family, KChIP1, appears specifically expressed in these cells. However, the functional role of this accessory subunit in A-type K(+) currents and interneuron excitability remains largely unknown. Thus, first we studied KChIP1 and Kv4.3 channel interactions in human embryonic kidney 293 (HEK293) cells and determined that KChIP1 coexpression modulated the biophysical properties of Kv4.3 A-type currents (faster recovery from inactivation, leftward shift of activation curve, faster rise time and slower decay) and this modulation was selectively prevented by KChIP1 short interfering RNA (siRNA) knockdown. Next, we evaluated the effects of KChIP1 down-regulation by siRNA on A-type K(+) currents in LM/RAD interneurons in slice cultures. Recovery from inactivation of A-type K(+) currents was slower after KChIP1 down-regulation but other properties were unchanged. In addition, down-regulation of KChIP1 levels did not affect action potential waveform and firing, but increased firing frequency during suprathreshold depolarizations, indicating that KChIP1 regulates interneuron excitability. The effects of KChIP1 down-regulation were cell-specific since CA1 pyramidal cells that do not express KChIP1 were unaffected. Overall, our findings suggest that KChIP1 interacts with Kv4.3 in LM/RAD interneurons, enabling faster recovery from inactivation of A-type currents and thus promoting stronger inhibitory control of firing during sustained activity.

  10. A novel slow hyperpolarization-activated potassium current (IK(SHA)) from a mouse hippocampal cell line.

    PubMed Central

    Wischmeyer, E; Karschin, A

    1997-01-01

    1. A slow hyperpolarization-activated inwardly rectifying K+ current (IK(SHA)) with novel characteristics was identified from the mouse embryonic hippocampus x neuroblastoma cell line HN9.10e. 2. The non-inactivating current activated negative to a membrane potential of -80 mV with slow and complex activation kinetics (tau act approximately 1-7 s) and a characteristic delay of 1-10 s (-80 to -140 mV) that was linearly dependent on the membrane potential. 3. Tail currents and instantaneous open channel currents determined through fast voltage ramps reversed at the K+ equilibrium potential (EK) indicating that primarily K+, but not Na+, permeated the channels. 4. IK(SHA) was unaffected by altering the intracellular Ca2+ concentration between approximately 0 and 10 microM, but was susceptible to block by 5 mM extracellular Ca2+, Ba2+ (Ki = 0.42 mM), and Cs+ (Ki = 2.77 mM) 5. In cells stably transformed with M2 muscarinic receptors, IK(SHA) was rapidly, but reversibly, suppressed by application of micromolar concentrations of muscarine. 6. At the single channel level K(SHA) channel openings were observed with the characteristic delay upon membrane hyperpolarization. Analysis of unitary currents revealed an inwardly rectifying I-V profile and a channel slope conductance of 7 pS. Channel activity persisted in the inside-out configuration for many minutes. 7. It is concluded that IK(SHA) in HN9.10e cells represents a novel K+ current, which is activated upon membrane hyperpolarization. It is functionally different from both classic inwardly rectifying IKir currents and other cationic hyperpolarization-activated IH currents that have been previously described in neuronal or glial cells. Images Figure 1 Figure 2 Figure 6 Figure 7 Figure 8 PMID:9401967

  11. Acetylcholine-induced potassium current of guinea pig outer hair cells: its dependence on a calcium influx through nicotinic-like receptors.

    PubMed

    Blanchet, C; Eróstegui, C; Sugasawa, M; Dulon, D

    1996-04-15

    The cholinergic efferent inhibition of mammalian outer hair cells (OHCs) is mediated by a hyperpolarizing K+ current. We have made whole-cell tight-seal recordings from single OHCs isolated from the guinea pig cochlea to characterize the mechanism by which acetylcholine (ACh) activates K+ channels. After ACh application, OHCs exhibited a biphasic response: an early depolarizing current preceding the predominant hyperpolarizing K+ current. The current-voltage (I-V) relationship of the ACh-induced response displayed an N-shape, suggesting the involvement of Ca2+ influx. When whole-cell recording was combined with confocal calcium imaging, we simultaneously observed the ACh-induced K+ current (IK(ACh)) and a Ca2+ response restricted to the synaptic area of the cell. This IK(ACh) could be prevented by loading OHCs with 10 mM of the fast Ca2+ buffer bis(2-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid (or BAPTA), therefore allowing the observation of the ACh-induced early current in isolation. This early current revealed nicotinic features because it activated with an intrinsic delay in the millisecond range, reversed nearly in between potassium and sodium equilibrium potentials, and was blocked by curare. However, it was strongly reduced in the absence of external Ca2+, and its I-V relationship displayed an unusual outward rectification at positive membrane potentials and an inward rectification below -60 mV. The results indicate that the cholinergic response of mammalian OHCs involves a "nicotinic-like" nonspecific cation channel through which Ca2+ enters and triggers activation of nearby Ca2+-dependent K+ channels.

  12. The inhibitory effects of nifedipine on outward voltage-gated potassium currents in mouse neuroblastoma N2A cells.

    PubMed

    Qiu, Xiao-Yue; Li, Kai; Li, Xiao-Qing; Li, Xian-Tao

    2016-06-01

    Voltage-gated K(+) (Kv) channels have a pivotal role in tuning the action potential duration and excitability in neuronal cells. Although Ca(2+) channel antagonist nifedipine exhibited an inhibitory effect on cardiac Kv currents, a possible action of nifedipine on neuronal Kv currents has not been fully investigated. The effects of nifedipine on elicited Kv currents were characterized using whole-cell recording in mouse neuroblastoma N2A cells. Exposure to nifedipine induced a dose-dependent inhibition of Kv currents with an IC50 value of 22.3±4.2μM and prolonged the time course of activation. The half-maximum activation potential was 1.6±1.7mV in control conditions and became 13.5±1.5mV in 50μM nifedipine. In addition, the decay rate of Kv currents was substantially accelerated by 39.5% at +60mV. For the voltage-dependent inactivation, the half-maximum inactivation potential was -13.8±0.8mV and strongly shifted to the left following treatment with 50μM nifedipine. Treatment with nifedipine exerted a strong influence on the activation and inactivation rate of Kv currents as well as an obvious leftward shift in the inactivation curve. These data indicated that nifedipine exerted an inhibitory effect on Kv currents in N2A cells. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  13. Submicromolar concentrations of zinc irreversibly reduce a calcium-dependent potassium current in rat hippocampal neurons in vitro.

    PubMed

    Sim, J A; Cherubini, E

    1990-01-01

    The action of the endogenous divalent cation zinc on Ca2+ and Ca2(+)-dependent currents was studied in rat hippocampal CA1 and CA3 neurons in vitro, by means of a single electrode voltage clamp technique. Bath application of zinc (0.5-1 microM) produced a small membrane depolarization associated with an increase in synaptic noise and cell excitability and a depression of the afterhyperpolarization following a train of action potentials. The effects on the afterhyperpolarization, could not be reversed on washout. In voltage-clamped neurons, zinc induced a steady inward current and reduced, at resting membrane potential, the peak amplitude of the outward current underlying the afterhyperpolarization, IAHP. In caesium loaded neurons (in the presence of tetrodotoxin and tetraethylammonium), zinc reduced the slow inactivating Ca2+ current activated from a holding potential of -40 mV. Similar results were observed with nickel and cobalt at comparable concentrations, with Zn2+ greater than Ni2+ greater than Co2+, in their order of potency. In contrast to nickel and cobalt the effects of zinc did not reverse on washout. These results suggest that low concentrations of zinc enhance cell excitability by reducing IAHP. In addition, zinc reduces the slow inactivating voltage-dependent Ca2+ current. The irreversible effect of this metal ion is compatible with a toxic, intracellular site of action.

  14. Adenosine Triphosphate (ATP) Inhibits Voltage-Sensitive Potassium Currents in Isolated Hensen's Cells and Nifedipine Protects Against Noise-Induced Hearing Loss in Guinea Pigs.

    PubMed

    Ye, Rui; Liu, Jun; Jia, Zhiying; Wang, Hongyang; Wang, YongAn; Sun, Wei; Wu, Xuan; Zhao, Zhifei; Niu, Baolong; Li, Xingqi; Dai, Guanghai; Li, Jianxiong

    2016-06-13

    BACKGROUND There is increasing evidence that adenosine triphosphate (ATP), a well-known neurotransmitter and neuromodulator in the central nervous system, plays an important role as an extracellular chemical messenger in the cochlea. MATERIAL AND METHODS Using a whole-cell recording technique, we studied the effects of ATP on isolated Hensen's cells, which are supporting cells in the cochlea, to determine if they are involved in the transduction of ions with hair cells. RESULTS ATP (0.1-10 µM) reduced the potassium current (IK+) in the majority of the recorded Hensen's cells (21 out of 25 cells). An inward current was also induced by high concentrations of ATP (100 µM to 10 mM), which was reversibly blocked by 100 µM suramin (a purinergic antagonist) and blocked by nifedipine (an L-type calcium channel blocker). After the cochleas were perfused with artificial perilymph solutions containing nifedipine and exposed to noise, the amplitude increase in the compound action potential (CAP) threshold and the reduction in cochlear microphonics was lower than when they were exposed to noise alone. CONCLUSIONS Our results suggest that ATP can block IK+ channels at a low concentration and induce an inward Ca2+ current at high concentrations, which is reversed by purinergic receptors. Nifedipine may have a partially protective effect on noise-induced hearing loss (NIHL).

  15. Potassium Current Is Not Affected by Long-Term Exposure to Ghrelin or GHRP-6 in Somatotropes GC Cells.

    PubMed

    Domínguez Mancera, Belisario; Monjaraz Guzman, Eduardo; Flores-Hernández, Jorge L V; Barrientos Morales, Manuel; Martínez Hernandez, José M; Hernández Beltran, Antonio; Cervantes Acosta, Patricia

    2013-01-01

    Ghrelin is a growth hormone (GH) secretagogue (GHS) and GHRP-6 is a synthetic peptide analogue; both act through the GHS receptor. GH secretion depends directly on the intracellular concentration of Ca(2+); this is determined from the intracellular reserves and by the entrance of Ca(2+) through the voltage-dependent calcium channels, which are activated by the membrane depolarization. Membrane potential is mainly determined by K(+) channels. In the present work, we investigated the effect of ghrelin (10 nM) or GHRP-6 (100 nM) for 96 h on functional expression of voltage-dependent K(+) channels in rat somatotropes: GC cell line. Physiological patch-clamp whole-cell recording was used to register the K(+) currents. With Cd(2+) (1 mM) and tetrodotoxin (1  μ m) in the bath solution recording, three types of currents were characterized on the basis of their biophysical and pharmacological properties. GC cells showed a K(+) current with a transitory component (I A) sensitive to 4-aminopyridine, which represents ~40% of the total outgoing current; a sustained component named delayed rectifier (I K), sensitive to tetraethylammonium; and a third type of K(+) current was recorded at potentials more negative than -80 mV, permitting the entrance of K(+) named inward rectifier (KIR). Chronic treatment with ghrelin or GHRP-6 did not modify the functional expression of K(+) channels, without significant changes (P < 0.05) in the amplitudes of the three currents observed; in addition, there were no modifications in their biophysical properties and kinetic activation or inactivation.

  16. Potassium cyanide

    Integrated Risk Information System (IRIS)

    Jump to main content . Integrated Risk Information System Recent Additions | Contact Us Search : All EPA IRIS • You are here : EPA Home • Research • Environmental Assessment • IRIS • IRIS Summaries Redirect Page As of September 28 , 2010 , the assessment summary for potassium cyanide is included in

  17. Distribution of transport current in a type-II superconductor studied by small-angle neutron scattering.

    PubMed

    Pautrat, A; Goupil, C; Simon, Ch; Charalambous, D; Forgan, E M; Lazard, G; Mathieu, P; Brûlet, A

    2003-02-28

    We report small-angle neutron scattering measurements on the vortex lattice in a PbIn polycrystal in the presence of an applied current. Using the rocking curves as a probe of the distribution of current in the sample, we observe that vortex pinning is due to the surface roughness. This leads to a surface current that persists in the flux-flow region. We show the influence of surface treatments on the distribution of this current.

  18. Potassium in diet

    MedlinePlus

    ... the diet; Hypokalemia - potassium in the diet; Chronic kidney disease - potassium in diet; Kidney failure - potassium in diet ... are also excellent sources of potassium. People with kidney problems, especially those on dialysis, should not eat ...

  19. Niflumic acid-induced increase in potassium currents in frog motor nerve terminals: effects on transmitter release.

    PubMed

    Miralles, F; Marsal, J; Peres, J; Solsona, C

    1996-04-01

    The actions of the nonsteroidal antiinflammatory drug niflumic acid were studied on frog neuromuscular preparations by conventional electrophysiological techniques. Niflumic acid reduced the amplitude and increased the latency of endplate potentials in a concentration-dependent manner. Neuromuscular junctions pretreated with niflumic acid (0.05-0.5 mM) showed much less depression than control when they were stimulated with trains of impulses. Inhibition of acetylcholine release was reverted by raising the extracellular Ca(2+) concentration but not by simply washing out the preparations with niflumic acid-free solutions. Pretreatment with indomethacin (0.1 mM), another nonsteroidal antiinflammatory drug, did not affect the niflumic acid-induced inhibition of evoked responses. Niflumic acid (0.1 mM) did not change the amplitude of miniature endplate potentials and had a dual action on the frequency of miniatures: it decreased their frequency at 0.1 mM whereas it produced an enormous increase in the rate of spontaneous discharge at 0.5 mM. Niflumic acid (0.1 - 1 mM) reversibly increased the amplitude and affected the kinetics of presynaptic voltage-activated K+ current and Ca(2+)-activated K(+) current in a concentration-dependent manner. Niflumic acid (0.1 - 1 mM) irreversibly decreased the amplitude and reversibly affected the kinetics of the nodal Na(+) current. Indomethacin (0.1 mM) had no effect on presynaptic currents. In conclusion, niflumic acid reduces acetylcholine release by increasing presynaptic K+ currents. This may shorten the depolarizing phase of the presynaptic action potential and may reduce the entry of Ca(2+) with each impulse.

  20. Gating currents from a Kv3 subfamily potassium channel: charge movement and modification by BDS-II toxin.

    PubMed

    Wang, Zhuren; Robertson, Brian; Fedida, David

    2007-11-01

    Kv3 channels have a major role in determining neuronal excitability, and are characterized by ultra-rapid kinetics of gating and a high activation threshold. However, the gating currents, which occur as a result of positional changes of the charged elements in the channel structure during activation, are not well understood. Here we report a study of gating currents from wild-type Kv3.2b channels, expressed in human embryonic kidney (HEK) cells to facilitate high time-resolution recording. On-gating currents (I(g,on)) had extremely rapid kinetics such that at +80 mV, the time constant for the decay of I(g,on) was only approximately 0.3 ms. Decay of I(g,on) appeared mono-exponential at all potentials studied, and in support of this, the charge-voltage (Q-V) relationship was fitted with a single Boltzmann function, supporting the idea that only one charge system is required to account for the time course of I(g,on) and the voltage dependence of Q(on). The voltage (V((1/2))) for half movement of gating charge was -8.4 +/- 4.0 mV (n = 6), which closely matches the voltage dependence of activation of Kv3.2b ionic currents reported before. Depolarizations to more positive potentials than 0 mV decreased the amplitude and slowed the decay of the off-gating currents (I(g,off)), suggesting that a rate-limiting step in opening was present in Kv3 channels as in Shaker and other Kv channels. Return of charge was negatively shifted along the potential axis with a V((1/2)) of Q(off) of -80.9 +/- 0.8 mV (n = 3), which allowed approximately 90% charge return upon repolarization to -100 mV. BDS-II toxin apparently reduced I(g,on), and greatly slowed the kinetics of I(g,on), while shifting the Q-V relationship in the depolarizing direction. However, the Q-V relationship remained well fitted by a single Boltzmann function. These data provide the first description of Kv3 gating currents and give further insight into the interaction of BDS toxins and Kv3 channels.

  1. Wenxin Keli attenuates ischemia-induced ventricular arrhythmias in rats: Involvement of L‑type calcium and transient outward potassium currents.

    PubMed

    Wang, Xi; Wang, Xin; Gu, Yongwei; Wang, Teng; Huang, Congxin

    2013-02-01

    Wenxin Keli is the first state‑sanctioned traditional Chinese medicine (TCM)-based antiarrhythmic drug. The present study aimed to examine whether long‑term treatment with Wenxin Keli reduces ischemia‑induced ventricular arrhythmias in rats in vivo, and if so, which mechanisms are involved. Male rats were treated with either saline (control group) or Wenxin Keli for 3 weeks and were subjected to myocardial ischemia for 30 min with assessment of the resulting ventricular arrhythmias. The L‑type calcium current (ICa,L) and transient outward potassium current (Ito) were measured by the patch clamp technique in normal rat cardiac ventricular myocytes. During the 30‑min ischemia, Wenxin Keli significantly reduced the incidence of ventricular fibrillation (VF) (P<0.05). The number of ventricular tachycardia (VT)+VF episodes and the severity of arrhythmias were significantly reduced by Wenxin Keli administration compared to the control group (P<0.05). In addition, Wenxin Keli inhibited ICa,L and Ito in a concentration‑dependent manner. These results suggest that long‑term treatment with Wenxin Keli may attenuate ischemia‑induced ventricular arrhythmias in rats and that ICa,L and Ito may be involved in this attenuation.

  2. Effects of Sleep Deprivation on Action Potential and Transient Outward Potassium Current in Ventricular Myocytes in Rats

    PubMed Central

    Fang, Zhou; Ren, Yi-Peng; Lu, Cai-Yi; Li, Yang; Xu, Qiang; Peng, Li; Fan, Yong-Yan

    2015-01-01

    Background Sleep deprivation contributes to the development and recurrence of ventricular arrhythmias. However, the electrophysiological changes in ventricular myocytes in sleep deprivation are still unknown. Material/Methods Sleep deprivation was induced by modified multiple platform technique. Fifty rats were assigned to control and sleep deprivation 1, 3, 5, and 7 days groups, and single ventricular myocytes were enzymatically dissociated from rat hearts. Action potential duration (APD) and transient outward current (Ito) were recorded using whole-cell patch clamp technique. Results Compared with the control group, the phases of APD of ventricular myocytes in 3, 5, and 7 days groups were prolonged and APD at 20% and 50% level of repolarization (APD20 and APD50) was significantly elongated (The APD20 values of control, 1, 3, 5, and 7 days groups: 5.66±0.16 ms, 5.77±0.20 ms, 8.28±0.30 ms, 11.56±0.32 ms, 13.24±0.56 ms. The APD50 values: 50.66±2.16 ms, 52.77±3.20 ms, 65.28±5.30 ms, 83.56±7.32 ms, 89.24±5.56 ms. P<0.01, n=18). The current densities of Ito significantly decreased. The current density-voltage (I–V) curve of Ito was vitally suppressed downward. The steady-state inactivation curve and steady-state activation curve of Ito were shifted to left and right, respectively, in sleep deprivation rats. The inactivation recovery time of Ito was markedly retarded and the time of closed-state inactivation was markedly accelerated in 3, 5, and 7 days groups. Conclusions APD of ventricular myocytes in sleep deprivation rats was significantly prolonged, which could be attributed to decreased activation and accelerated inactivation of Ito. PMID:25694200

  3. Transient outward potassium current, ‘Ito’, phenotypes in the mammalian left ventricle: underlying molecular, cellular and biophysical mechanisms

    PubMed Central

    Patel, Sangita P; Campbell, Donald L

    2005-01-01

    At least two functionally distinct transient outward K+ current (Ito) phenotypes can exist across the free wall of the left ventricle (LV). Based upon their voltage-dependent kinetics of recovery from inactivation, these two phenotypes are designated ‘Ito,fast’ (recovery time constants on the order of tens of milliseconds) and ‘Ito,slow’ (recovery time constants on the order of thousands of milliseconds). Depending upon species, either Ito,fast, Ito,slow or both current phenotypes may be expressed in the LV free wall. The expression gradients of these two Ito phenotypes across the LV free wall are typically heterogeneous and, depending upon species, may consist of functional phenotypic gradients of both Ito,fast and Ito,slow and/or density gradients of either phenotype. We review the present evidence (molecular, biophysical, electrophysiological and pharmacological) for Kv4.2/4.3 α subunits underlying LV Ito,fast and Kv1.4 α subunits underlying LV Ito,slow and speculate upon the potential roles of each of these currents in determining frequency-dependent action potential characteristics of LV subepicardial versus subendocardial myocytes in different species. We also review the possible functional implications of (i) ancillary subunits that regulate Kv1.4 and Kv4.2/4.3 (Kvβ subunits, DPPs), (ii) KChIP2 isoforms, (iii) spider toxin-mediated block of Kv4.2/4.3 (Heteropoda toxins, phrixotoxins), and (iv) potential mechanisms of modulation of Ito,fast and Ito,slow by cellular redox state, [Ca2+]i and kinase-mediated phosphorylation. Ito phenotypic activation and state-dependent gating models and molecular structure–function relationships are also discussed. PMID:15831535

  4. Effects of sleep deprivation on action potential and transient outward potassium current in ventricular myocytes in rats.

    PubMed

    Fang, Zhou; Ren, Yi-Peng; Lu, Cai-Yi; Li, Yang; Xu, Qiang; Peng, Li; Fan, Yong-Yan

    2015-02-19

    Sleep deprivation contributes to the development and recurrence of ventricular arrhythmias. However, the electrophysiological changes in ventricular myocytes in sleep deprivation are still unknown. Sleep deprivation was induced by modified multiple platform technique. Fifty rats were assigned to control and sleep deprivation 1, 3, 5, and 7 days groups, and single ventricular myocytes were enzymatically dissociated from rat hearts. Action potential duration (APD) and transient outward current (Ito) were recorded using whole-cell patch clamp technique. Compared with the control group, the phases of APD of ventricular myocytes in 3, 5, and 7 days groups were prolonged and APD at 20% and 50% level of repolarization (APD20 and APD50) was significantly elongated (The APD20 values of control, 1, 3, 5, and 7 days groups: 5.66±0.16 ms, 5.77±0.20 ms, 8.28±0.30 ms, 11.56±0.32 ms, 13.24±0.56 ms. The APD50 values: 50.66±2.16 ms, 52.77±3.20 ms, 65.28±5.30 ms, 83.56±7.32 ms, 89.24±5.56 ms. P<0.01, n=18). The current densities of Ito significantly decreased. The current density-voltage (I-V) curve of Ito was vitally suppressed downward. The steady-state inactivation curve and steady-state activation curve of Ito were shifted to left and right, respectively, in sleep deprivation rats. The inactivation recovery time of Ito was markedly retarded and the time of closed-state inactivation was markedly accelerated in 3, 5, and 7 days groups. APD of ventricular myocytes in sleep deprivation rats was significantly prolonged, which could be attributed to decreased activation and accelerated inactivation of Ito.

  5. Diethylcarbamazine Increases Activation of Voltage-Activated Potassium (SLO-1) Currents in Ascaris suum and Potentiates Effects of Emodepside

    PubMed Central

    Buxton, Samuel K.; Robertson, Alan P.; Martin, Richard J.

    2014-01-01

    Diethylcarbamazine is a drug that is used for the treatment of filariasis in humans and animals; it also has effects on intestinal nematodes, but its mechanism of action remains unclear. Emodepside is a resistance-busting anthelmintic approved for treating intestinal parasitic nematodes in animals. The novel mode of action and resistance-breaking properties of emodepside has led to its use against intestinal nematodes of animals, and as a candidate drug for treating filarial parasites. We have previously demonstrated effects of emodepside on SLO-1 K+-like currents in Ascaris suum. Here, we demonstrate that diethylcarbamazine, which has been proposed to work through host mediated effects, has direct effects on a nematode parasite, Ascaris suum. It increases activation of SLO-1 K+ currents and potentiates effects of emodepside. Our results suggest consideration of the combination of emodepside and diethylcarbamazine for therapy, which is predicted to be synergistic. The mode of action of diethylcarbamazine may involve effects on parasite signaling pathways (including nitric oxide) as well as effects mediated by host inflammatory mediators. PMID:25411836

  6. Dual modulation of inward rectifier potassium currents in olfactory neuronal cells by promiscuous G protein coupling of the oxytocin receptor.

    PubMed

    Gravati, Marta; Busnelli, Marta; Bulgheroni, Elisabetta; Reversi, Alessandra; Spaiardi, Paolo; Parenti, Marco; Toselli, Mauro; Chini, Bice

    2010-09-01

    Oxytocin receptor is a seven transmembrane receptor widely expressed in the CNS that triggers G(i) or G(q) protein-mediated signaling cascades leading to the regulation of a variety of neuroendocrine and cognitive functions. We decided to investigate whether and how the promiscuous receptor/G protein coupling affects neuronal excitability. As an experimental model, we used the immortalized gonadotropin-releasing hormone-positive GN11 cell line displaying the features of immature, migrating olfactory neurons. Using RT-PCR analysis, we detected the presence of oxytocin receptors whose stimulation by oxytocin led to the accumulation of inositol phosphates and to the inhibition of cell proliferation, and the expression of several inward rectifier (IR) K+ channel subtypes. Moreover, electrophysiological and pharmacological inspections using whole-cell patch-clamp recordings evidenced that in GN11 cells, IR channel subtypes are responsive to oxytocin. In particular, we found that: (i) peptide activation of receptor either inhibited or stimulated IR conductances, and (ii) IR current inhibition was mediated by a pertussis toxin-resistant G protein presumably of the G(q/11) subtype, and by phospholipase C, whereas IR current activation was achieved via receptor coupling to a pertussis toxin-sensitive G(i/o) protein. The findings suggest that neuronal excitability might be tuned by a single peptide receptor that mediates opposing effects on distinct K+ channels through the promiscuous coupling to different G proteins.

  7. Prolonged Action Potential and After depolarizations Are Not due to Changes in Potassium Currents in NOS3 Knockout Ventricular Myocytes.

    PubMed

    Wang, Honglan; Bonilla, Ingrid M; Huang, Xin; He, Quanhua; Kohr, Mark J; Carnes, Cynthia A; Ziolo, Mark T

    2012-01-01

    Ventricular myocytes deficient in endothelial nitric oxide synthase (NOS3(-/-)) exhibit prolonged action potential (AP) duration and enhanced spontaneous activity (early and delayed afterdepolarizations) during β-adrenergic (β-AR) stimulation. Studies have shown that nitric oxide is able to regulate various K(+) channels. Our objective was to examine if NOS3(-/-) myocytes had altered K(+) currents. APs, transient outward (I(to)), sustained (I(Ksus)), and inward rectifier (I(K1)) K(+) currents were measured in NOS3(-/-) and wild-type (WT) myocytes. During β-AR stimulation, AP duration (measured as 90% repolarization-APD(90)) was prolonged in NOS3(-/-) compared to WT myocytes. Nevertheless, we did not observe differences in I(to), I(Ksus), or I(K1) between WT and NOS3(-/-) myocytes. Our previous work showed that NOS3(-/-) myocytes had a greater Ca(2+) influx via L-type Ca(2+) channels with β-AR stimulation. Thus, we measured β-AR-stimulated SR Ca(2+) load and found a greater increase in NOS3(-/-) versus WT myocytes. Hence, our data suggest that the prolonged AP in NOS3(-/-) myocytes is not due to changes in I(to), I(Ksus), or I(K1). Furthermore, the increase in spontaneous activity in NOS3(-/-) myocytes may be due to a greater increase in SR Ca(2+) load. This may have important implications for heart failure patients, where arrhythmias are increased and NOS3 expression is decreased.

  8. Diethylcarbamazine increases activation of voltage-activated potassium (SLO-1) currents in Ascaris suum and potentiates effects of emodepside.

    PubMed

    Buxton, Samuel K; Robertson, Alan P; Martin, Richard J

    2014-01-01

    Diethylcarbamazine is a drug that is used for the treatment of filariasis in humans and animals; it also has effects on intestinal nematodes, but its mechanism of action remains unclear. Emodepside is a resistance-busting anthelmintic approved for treating intestinal parasitic nematodes in animals. The novel mode of action and resistance-breaking properties of emodepside has led to its use against intestinal nematodes of animals, and as a candidate drug for treating filarial parasites. We have previously demonstrated effects of emodepside on SLO-1 K+-like currents in Ascaris suum. Here, we demonstrate that diethylcarbamazine, which has been proposed to work through host mediated effects, has direct effects on a nematode parasite, Ascaris suum. It increases activation of SLO-1 K+ currents and potentiates effects of emodepside. Our results suggest consideration of the combination of emodepside and diethylcarbamazine for therapy, which is predicted to be synergistic. The mode of action of diethylcarbamazine may involve effects on parasite signaling pathways (including nitric oxide) as well as effects mediated by host inflammatory mediators.

  9. Regulation of the resting potential of rabbit pulmonary artery myocytes by a low threshold, O2-sensing potassium current

    PubMed Central

    Osipenko, Oleg N; Mark Evans, A; Gurney, Alison M

    1997-01-01

    The contributions of specific K+ currents to the resting membrane potential of rabbit isolated, pulmonary artery myocytes, and their modulation by hypoxia, were investigated by use of the whole-cell, patch-clamp technique.In the presence of 10 μM glibenclamide the resting potential (−50±4 mV, n=18) was unaffected by 10 μM tetraethylammonium ions, 200 nM charybdotoxin, 200  nM iberiotoxin, 100 μM ouabain or 100 μM digitoxin. The negative potential was therefore maintained without ATP-sensitive (KATP) or large conductance Ca2+-sensitive (BKCa) K channels, and without the Na+-K+ATPase.The resting potential, the delayed rectifier current (IK(V)) and the A-like K+ current (IK(A)) were all reduced in a concentration-dependent manner by 4-aminopyridine (4-AP) and by quinine.4-AP was equally potent at reducing the resting potential and IK(V), 10 mM causing depolarization from −44 mV to −22 mV with accompanying inhibition of IK(V) by 56% and IK(A) by 79%. In marked contrast, the effects of quinine on resting potential were poorly correlated with its effects on both IK(A) and IK(V). At 10 mM, quinine reduced IK(V) and IK(A) by 47% and 38%, respectively, with no change in the resting potential. At 100 μM, both currents were almost abolished while the resting potential was reduced <50%. Raising the concentration to 1 mM had little further effect on IK(A) or IK(V), but essentially abolished the resting potential.Reduction of the resting potential by quinine was correlated with inhibition of a voltage-gated, low threshold, non-inactivating K+ current, IK(N). Thus, 100 μM quinine reduced both IK(N) and the resting potential by around 50%.The resting membrane potential was the same whether measured after clamping the cell at −80 mV, or immediately after a prolonged period of depolarization at 0 mV, which inactivated IK(A) and IK(V), but not IK(N).When exposed to a hypoxic solution, the O2 tension near the cell fell from 125±6 to 14

  10. The calcium-independent transient outward potassium current in isolated ferret right ventricular myocytes. I. Basic characterization and kinetic analysis

    PubMed Central

    1993-01-01

    Enzymatically isolated myocytes from ferret right ventricles (12-16 wk, male) were studied using the whole cell patch clamp technique. The macroscopic properties of a transient outward K+ current I(to) were quantified. I(to) is selective for K+, with a PNa/PK of 0.082. Activation of I(to) is a voltage-dependent process, with both activation and inactivation being independent of Na+ or Ca2+ influx. Steady-state inactivation is well described by a single Boltzmann relationship (V1/2 = -13.5 mV; k = 5.6 mV). Substantial inactivation can occur during a subthreshold depolarization without any measurable macroscopic current. Both development of and recovery from inactivation are well described by single exponential processes. Ensemble averages of single I(to) channel currents recorded in cell-attached patches reproduce macroscopic I(to) and indicate that inactivation is complete at depolarized potentials. The overall inactivation/recovery time constant curve has a bell-shaped potential dependence that peaks between -10 and -20 mV, with time constants (22 degrees C) ranging from 23 ms (-90 mV) to 304 ms (-10 mV). Steady-state activation displays a sigmoidal dependence on membrane potential, with a net aggregate half- activation potential of +22.5 mV. Activation kinetics (0 to +70 mV, 22 degrees C) are rapid, with I(to) peaking in approximately 5-15 ms at +50 mV. Experiments conducted at reduced temperatures (12 degrees C) demonstrate that activation occurs with a time delay. A nonlinear least- squares analysis indicates that three closed kinetic states are necessary and sufficient to model activation. Derived time constants of activation (22 degrees C) ranged from 10 ms (+10 mV) to 2 ms (+70 mV). Within the framework of Hodgkin-Huxley formalism, Ito gating can be described using an a3i formulation. PMID:8505627

  11. 78 FR 33768 - Airworthiness Directives; Agusta S.p.A. (Type Certificate Currently Held by AgustaWestland S.p.A...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-05

    ... Directives; Agusta S.p.A. (Type Certificate Currently Held by AgustaWestland S.p.A.) Helicopters (Agusta...'' address between 9 a.m. and 5 p.m., Monday through Friday, except Federal holidays. Examining the AD Docket... Operations Office between 9 a.m. and 5 p.m., Monday through Friday, except Federal holidays. The AD...

  12. Attenuated outward potassium currents in carotid body glomus cells of heart failure rabbit: involvement of nitric oxide

    PubMed Central

    Li, Yu-Long; Sun, Shu-Yu; Overholt, Jeffery L; Prabhakar, Nanduri R; Rozanski, George J; Zucker, Irving H; Schultz, Harold D

    2004-01-01

    It has been shown that peripheral chemoreceptor sensitivity is enhanced in both clinical and experimental heart failure (HF) and that impairment of nitric oxide (NO) production contributes to this enhancement. In order to understand the cellular mechanisms associated with the alterations of chemoreceptor function and the actions of NO in the carotid body (CB), we compared the outward K+ currents (IK) of glomus cells in sham rabbits with that in HF rabbits and monitored the effects of NO on these currents. Ik was measured in glomus cells using conventional and perforated whole-cell configurations. IK was attenuated in glomus cells of HF rabbits, and their resting membrane potentials (−34.7 ± 1.0 mV) were depolarized as compared with those in sham rabbits (−47.2 ± 1.9 mV). The selective Ca2+-dependent K+ channel (KCa) blocker iberiotoxin (IbTx, 100 nm) reduced IK in glomus cells from sham rabbits, but had no effect on IK from HF rabbits. In perforated whole-cell mode, the NO donor SNAP (100 μm) increased IK in glomus cells from HF rabbits to a greater extent than that in sham rabbits (P < 0.01), and IbTx inhibited the effects of SNAP. However, in conventional whole-cell mode, SNAP had no effect. Nω-nitro-L-arginine (L-NNA, NO synthase inhibitor) decreased Ik in sham rabbits but not in HF rabbits. The guanylate cyclase inhibitor 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ) inhibited the effect of SNAP on Ik. These results demonstrate that IK is reduced in CB glomus cells from HF rabbits. This effect is due mainly to the suppression of KCa channel activity caused by decreased availability of NO. In addition, intracellular cGMP is necessary for the KCa channel modulation by NO. PMID:14673183

  13. Prolonged Action Potential and After depolarizations Are Not due to Changes in Potassium Currents in NOS3 Knockout Ventricular Myocytes

    PubMed Central

    Wang, Honglan; Bonilla, Ingrid M.; Huang, Xin; He, Quanhua; Kohr, Mark J.; Carnes, Cynthia A.; Ziolo, Mark T.

    2012-01-01

    Ventricular myocytes deficient in endothelial nitric oxide synthase (NOS3−/−) exhibit prolonged action potential (AP) duration and enhanced spontaneous activity (early and delayed afterdepolarizations) during β-adrenergic (β-AR) stimulation. Studies have shown that nitric oxide is able to regulate various K+ channels. Our objective was to examine if NOS3−/− myocytes had altered K+ currents. APs, transient outward (I to), sustained (I Ksus), and inward rectifier (I K1) K+ currents were measured in NOS3−/− and wild-type (WT) myocytes. During β-AR stimulation, AP duration (measured as 90% repolarization-APD90) was prolonged in NOS3−/− compared to WT myocytes. Nevertheless, we did not observe differences in I to, I Ksus, or I K1 between WT and NOS3−/− myocytes. Our previous work showed that NOS3−/− myocytes had a greater Ca2+ influx via L-type Ca2+ channels with β-AR stimulation. Thus, we measured β-AR-stimulated SR Ca2+ load and found a greater increase in NOS3−/− versus WT myocytes. Hence, our data suggest that the prolonged AP in NOS3−/− myocytes is not due to changes in I to, I Ksus, or I K1. Furthermore, the increase in spontaneous activity in NOS3−/− myocytes may be due to a greater increase in SR Ca2+ load. This may have important implications for heart failure patients, where arrhythmias are increased and NOS3 expression is decreased. PMID:22970362

  14. Mapping Potassium

    NASA Image and Video Library

    2015-04-16

    During the first year of NASA MESSENGER orbital mission, the spacecraft GRS instrument measured the elemental composition of Mercury surface materials. mong the most important discoveries from the GRS was the observation of higher abundances of the moderately volatile elements potassium, sodium, and chlorine than expected from previous scientific models and theories. Particularly high concentrations of these elements were observed at high northern latitudes, as illustrated in this potassium abundance map, which provides a view of the surface centered at 60° N latitude and 120° E longitude. This map was the first elemental map ever made of Mercury's surface and is to-date the only map to report absolute elemental concentrations, in comparison to element ratios. Prior to MESSENGER's arrival at Mercury, scientists expected that the planet would be depleted in moderately volatile elements, as is the case for our Moon. The unexpectedly high abundances observed with the GRS have forced a reevaluation of our understanding of the formation and evolution of Mercury. In addition, the K map provided the first evidence for distinct geochemical terranes on Mercury, as the high-potassium region was later found to also be distinct in its low Mg/Si, Ca/Si, S/Si, and high Na/Si and Cl/Si abundances. Instrument: Gamma-Ray Spectrometer (GRS) http://photojournal.jpl.nasa.gov/catalog/PIA19414

  15. Deletion of Kv4.2 gene eliminates dendritic A-type K+ current and enhances induction of long-term potentiation in hippocampal CA1 pyramidal neurons.

    PubMed

    Chen, Xixi; Yuan, Li-Lian; Zhao, Cuiping; Birnbaum, Shari G; Frick, Andreas; Jung, Wonil E; Schwarz, Thomas L; Sweatt, J David; Johnston, Daniel

    2006-11-22

    Dendritic, backpropagating action potentials (bAPs) facilitate the induction of Hebbian long-term potentiation (LTP). Although bAPs in distal dendrites of hippocampal CA1 pyramidal neurons are attenuated when propagating from the soma, their amplitude can be increased greatly via downregulation of dendritic A-type K+ currents. The channels that underlie these currents thus may represent a key regulatory component of the signaling pathways that lead to synaptic plasticity. We directly tested this hypothesis by using Kv4.2 knock-out mice. Deletion of the Kv4.2 gene and a loss of Kv4.2 protein resulted in a specific and near-complete elimination of A-type K+ currents from the apical dendrites of CA1 pyramidal neurons. The absence of dendritic Kv4.2-encoded A-type K+ currents led to an increase of bAP amplitude and an increase of concurrent Ca2+ influx. Furthermore, CA1 pyramidal neurons lacking dendritic A-type K+ currents from Kv4.2 knock-out mice exhibited a lower threshold than those of wild-type littermates for LTP induction with the use of a theta burst pairing protocol. LTP triggered with the use of a saturating protocol, on the other hand, remained indistinguishable between Kv4.2 knock-out and wild-type neurons. Our results support the hypothesis that dendritic A-type K+ channels, composed of Kv4.2 subunits, regulate action potential backpropagation and the induction of specific forms of synaptic plasticity.

  16. Origin of the potassium and voltage dependence of the cardiac inwardly rectifying K-current (IK1).

    PubMed Central

    Pennefather, P; Oliva, C; Mulrine, N

    1992-01-01

    Using various voltage clamp protocols, we have examined the activation and deactivation kinetics of IK1 recorded in dissociated myocytes obtained from canine purkinje fibers. Exponential current relaxations following step changes of the membrane potential were characterized at several different K levels (5, 12, 42, and 82 mM) and several voltages (K reversal potential +/- 40 mV). We have interpreted our data according to a K-activated, K-channel model of IK1 gating. Our data suggests that at least two binding sites for extracellular K must be occupied before the channel opens and occupancy of about three more higher affinity sites for K on the open channel will slow the closing of that channel. In our model, the voltage dependency of gating arises from a combination of three voltage dependent steps: (a) isomerization between open and closed states, (b) binding of K, and (c) occupancy of the channel by internal Mg. Lowering internal K to 40 mM causes major changes in the voltage and K dependence of IK1 gating. However, these changes could be accounted for in our model by relatively small (approximately 20 to 30 mV) shifts in the voltage dependence of several of the steps that govern gating. Our data further suggest that there is an interaction between both extracellular and intracellular K levels and the ability of intracellular Mg to block the IK1 channel. PMID:1547332

  17. High firing rate of neonatal hippocampal interneurons is caused by attenuation of afterhyperpolarizing potassium currents by tonically active kainate receptors.

    PubMed

    Segerstråle, Mikael; Juuri, Juuso; Lanore, Frédéric; Piepponen, Petteri; Lauri, Sari E; Mulle, Christophe; Taira, Tomi

    2010-05-12

    In the neonatal hippocampus, the activity of interneurons shapes early network bursts that are important for the establishment of neuronal connectivity. However, mechanisms controlling the firing of immature interneurons remain elusive. We now show that the spontaneous firing rate of CA3 stratum lucidum interneurons markedly decreases during early postnatal development because of changes in the properties of GluK1 (formerly known as GluR5) subunit-containing kainate receptors (KARs). In the neonate, activation of KARs by ambient glutamate exerts a tonic inhibition of the medium-duration afterhyperpolarization (mAHP) by a G-protein-dependent mechanism, permitting a high interneuronal firing rate. During development, the amplitude of the apamine-sensitive K+ currents responsible for the mAHP increases dramatically because of decoupling between KAR activation and mAHP modulation, leading to decreased interneuronal firing. The developmental shift in the KAR function and its consequences on interneuronal activity are likely to have a fundamental role in the maturation of the synchronous neuronal oscillations typical for adult hippocampal circuitry.

  18. JMV5656, A Novel Derivative of TLQP-21, Triggers the Activation of a Calcium-Dependent Potassium Outward Current in Microglial Cells

    PubMed Central

    Rivolta, Ilaria; Binda, Anna; Molteni, Laura; Rizzi, Laura; Bresciani, Elena; Possenti, Roberta; Fehrentz, Jean-Alain; Verdié, Pascal; Martinez, Jean; Omeljaniuk, Robert J.; Locatelli, Vittorio; Torsello, Antonio

    2017-01-01

    TLQP-21 (TLQPPASSRRRHFHHALPPAR) is a multifunctional peptide that is involved in the control of physiological functions, including feeding, reproduction, stress responsiveness, and general homeostasis. Despite the huge interest in TLQP-21 biological activity, very little is known about its intracellular mechanisms of action. In microglial cells, TLQP-21 stimulates increases of intracellular Ca2+ that may activate functions, including proliferation, migration, phagocytosis and production of inflammatory molecules. Our aim was to investigate whether JMV5656 (RRRHFHHALPPAR), a novel short analogue of TLQP-21, stimulates intracellular Ca2+ in the N9 microglia cells, and whether this Ca2+ elevation is coupled with the activation Ca2+-sensitive K+ channels. TLQP-21 and JMV5656 induced a sharp, dose-dependent increment in intracellular calcium. In 77% of cells, JMV5656 also caused an increase in the total outward currents, which was blunted by TEA (tetraethyl ammonium chloride), a non-selective blocker of voltage-dependent and Ca2+-activated potassium (K+) channels. Moreover, the effects of ion channel blockers charybdotoxin and iberiotoxin, suggested that multiple calcium-activated K+ channel types drove the outward current stimulated by JMV5656. Additionally, inhibition of JMV5656-stimulated outward currents by NS6180 (4-[[3-(trifluoromethyl)phenyl]methyl]-2H-1,4 benzothiazin-3(4H)-one) and TRAM-34 (triarylmethane-34), indicated that KCa3.1 channels are involved in this JMV5656 mechanisms of action. In summary, we demonstrate that, in N9 microglia cells, the interaction of JMV5656 with the TLQP-21 receptors induced an increase in intracellular Ca2+, and, following extracellular Ca2+ entry, the opening of KCa3.1 channels. PMID:28280458

  19. The magnitudes of hyperpolarization-activated and low-voltage-activated potassium currents co-vary in neurons of the ventral cochlear nucleus

    PubMed Central

    Cao, Xiao-Jie

    2011-01-01

    In the ventral cochlear nucleus (VCN), neurons have hyperpolarization-activated conductances, which in some cells are enormous, that contribute to the ability of neurons to convey acoustic information in the timing of their firing by decreasing the input resistance and speeding-up voltage changes. Comparisons of the electrophysiological properties of neurons in the VCN of mutant mice that lack the hyperpolarization-activated cyclic nucleotide-gated channel α subunit 1 (HCN1−/−) (Nolan et al. 2003) with wild-type controls (HCN1+/+) and with outbred ICR mice reveal that octopus, T stellate, and bushy cells maintain their electrophysiological distinctions in all strains. Hyperpolarization-activated (Ih) currents were smaller and slower, input resistances were higher, and membrane time constants were longer in HCN1−/− than in HCN1+/+ in octopus, bushy, and T stellate cells. There were significant differences in the average magnitudes of Ih, input resistances, and time constants between HCN1+/+ and ICR mice, but the resting potentials did not differ between strains. Ih is opposed by a low-voltage-activated potassium (IKL) current in bushy and octopus cells, whose magnitudes varied widely between neuronal types and between strains. The magnitudes of Ih and IKL were correlated across neuronal types and across mouse strains. Furthermore, these currents balanced one another at the resting potential in individual cells. The magnitude of Ih and IKL is linked in bushy and octopus cells and varies not only between HCN1−/− and HCN1+/+ but also between “wild-type” strains of mice, raising the question to what extent the wild-type strains reflect normal mice. PMID:21562186

  20. JMV5656, A Novel Derivative of TLQP-21, Triggers the Activation of a Calcium-Dependent Potassium Outward Current in Microglial Cells.

    PubMed

    Rivolta, Ilaria; Binda, Anna; Molteni, Laura; Rizzi, Laura; Bresciani, Elena; Possenti, Roberta; Fehrentz, Jean-Alain; Verdié, Pascal; Martinez, Jean; Omeljaniuk, Robert J; Locatelli, Vittorio; Torsello, Antonio

    2017-01-01

    TLQP-21 (TLQPPASSRRRHFHHALPPAR) is a multifunctional peptide that is involved in the control of physiological functions, including feeding, reproduction, stress responsiveness, and general homeostasis. Despite the huge interest in TLQP-21 biological activity, very little is known about its intracellular mechanisms of action. In microglial cells, TLQP-21 stimulates increases of intracellular Ca(2+) that may activate functions, including proliferation, migration, phagocytosis and production of inflammatory molecules. Our aim was to investigate whether JMV5656 (RRRHFHHALPPAR), a novel short analogue of TLQP-21, stimulates intracellular Ca(2+) in the N9 microglia cells, and whether this Ca(2+) elevation is coupled with the activation Ca(2+)-sensitive K(+) channels. TLQP-21 and JMV5656 induced a sharp, dose-dependent increment in intracellular calcium. In 77% of cells, JMV5656 also caused an increase in the total outward currents, which was blunted by TEA (tetraethyl ammonium chloride), a non-selective blocker of voltage-dependent and Ca(2+)-activated potassium (K(+)) channels. Moreover, the effects of ion channel blockers charybdotoxin and iberiotoxin, suggested that multiple calcium-activated K(+) channel types drove the outward current stimulated by JMV5656. Additionally, inhibition of JMV5656-stimulated outward currents by NS6180 (4-[[3-(trifluoromethyl)phenyl]methyl]-2H-1,4 benzothiazin-3(4H)-one) and TRAM-34 (triarylmethane-34), indicated that KCa3.1 channels are involved in this JMV5656 mechanisms of action. In summary, we demonstrate that, in N9 microglia cells, the interaction of JMV5656 with the TLQP-21 receptors induced an increase in intracellular Ca(2+), and, following extracellular Ca(2+) entry, the opening of KCa3.1 channels.

  1. The magnitudes of hyperpolarization-activated and low-voltage-activated potassium currents co-vary in neurons of the ventral cochlear nucleus.

    PubMed

    Cao, Xiao-Jie; Oertel, Donata

    2011-08-01

    In the ventral cochlear nucleus (VCN), neurons have hyperpolarization-activated conductances, which in some cells are enormous, that contribute to the ability of neurons to convey acoustic information in the timing of their firing by decreasing the input resistance and speeding-up voltage changes. Comparisons of the electrophysiological properties of neurons in the VCN of mutant mice that lack the hyperpolarization-activated cyclic nucleotide-gated channel α subunit 1 (HCN1(-/-)) (Nolan et al. 2003) with wild-type controls (HCN1(+/+)) and with outbred ICR mice reveal that octopus, T stellate, and bushy cells maintain their electrophysiological distinctions in all strains. Hyperpolarization-activated (I(h)) currents were smaller and slower, input resistances were higher, and membrane time constants were longer in HCN1(-/-) than in HCN1(+/+) in octopus, bushy, and T stellate cells. There were significant differences in the average magnitudes of I(h), input resistances, and time constants between HCN1(+/+) and ICR mice, but the resting potentials did not differ between strains. I(h) is opposed by a low-voltage-activated potassium (I(KL)) current in bushy and octopus cells, whose magnitudes varied widely between neuronal types and between strains. The magnitudes of I(h) and I(KL) were correlated across neuronal types and across mouse strains. Furthermore, these currents balanced one another at the resting potential in individual cells. The magnitude of I(h) and I(KL) is linked in bushy and octopus cells and varies not only between HCN1(-/-) and HCN1(+/+) but also between "wild-type" strains of mice, raising the question to what extent the wild-type strains reflect normal mice.

  2. Enhanced critical current properties in Ba0.6K0.4+xFe2As2 superconductor by overdoping of potassium

    NASA Astrophysics Data System (ADS)

    Wang, Chunlei; Wang, Lei; Gao, Zhaoshun; Yao, Chao; Wang, Dongliang; Qi, Yanpeng; Zhang, Xianping; Ma, Yanwei

    2011-01-01

    Phase-pure polycrystalline Ba0.6K0.4+xFe2As2 with 0≤x≤0.1 were prepared using a one-step solid-state reaction method. We found that overdoping of potassium can improve the critical current density (Jc). High-field Jc for samples with x =0.1 is three times higher than that for samples with x =0. Overdoping of K has minimal effect on the critical transition temperature (Tc). Less than 0.5 K degradations in Tc was measured for samples with x =0.1. Transmission electron microscopy (TEM) revealed high concentration of dislocations in samples with x =0.1, resulting in enhanced flux pining. Further analyses on magnetization loops for powder samples confirm that K overdoping can promote intragrain Jc. Our results indicate that slight excess of K in Ba0.6K0.4Fe2As2 superconductor is beneficial to high-field applications.

  3. Role of Apamin-Sensitive Calcium-Activated Small-Conductance Potassium Currents on the Mechanisms of Ventricular Fibrillation in Pacing-Induced Failing Rabbit Hearts.

    PubMed

    Yin, Dechun; Hsieh, Yu-Cheng; Tsai, Wei-Chung; Wu, Adonis Zhi-Yang; Jiang, Zhaolei; Chan, Yi-Hsin; Xu, Dongzhu; Yang, Na; Shen, Changyu; Chen, Zhenhui; Lin, Shien-Fong; Chen, Peng-Sheng; Everett, Thomas H

    2017-02-01

    Ventricular fibrillation (VF) during heart failure is characterized by stable reentrant spiral waves (rotors). Apamin-sensitive small-conductance calcium-activated potassium currents (IKAS) are heterogeneously upregulated in failing hearts. We hypothesized that IKAS influences the location and stability of rotors during VF. Optical mapping was performed on 9 rabbit hearts with pacing-induced heart failure. The epicardial right ventricular and left ventricular surfaces were simultaneously mapped in a Langendorff preparation. At baseline and after apamin (100 nmol/L) infusion, the action potential duration (APD80) was determined, and VF was induced. Areas with a >50% increase in the maximum action potential duration (ΔAPD) after apamin infusion were considered to have a high IKAS distribution. At baseline, the distribution density of phase singularities during VF in high IKAS distribution areas was higher than in other areas (0.0035±0.0011 versus 0.0014±0.0010 phase singularities/pixel; P=0.004). In addition, high dominant frequencies also colocalized to high IKAS distribution areas (26.0 versus 17.9 Hz; P=0.003). These correlations were eliminated during VF after apamin infusion, as the number of phase singularities (17.2 versus 11.0; P=0.009) and dominant frequencies (22.1 versus 16.2 Hz; P=0.022) were all significantly decreased. In addition, reentrant spiral waves became unstable after apamin infusion, and the duration of VF decreased. The IKAS current influences the mechanism of VF in failing hearts as phase singularities, high dominant frequencies, and reentrant spiral waves all correlated to areas of high IKAS. Apamin eliminated this relationship and reduced VF vulnerability. © 2017 American Heart Association, Inc.

  4. Small Conductance Calcium-Activated Potassium Current is Activated During Hypokalemia and Masks Short Term Cardiac Memory Induced by Ventricular Pacing

    PubMed Central

    Chan, Yi-Hsin; Tsai, Wei-Chung; Ko, Jum-Suk; Yin, Dechun; Chang, Po-Cheng; Rubart, Michael; Weiss, James N.; Everett, Thomas; Lin, Shien-Fong; Chen, Peng-Sheng

    2015-01-01

    Background Hypokalemia increases the vulnerability to ventricular fibrillation (VF). We hypothesize that the apamin-sensitive small conductance calcium-activated potassium current (IKAS) is activated during hypokalemia and that IKAS blockade is proarrhythmic. Methods and Results Optical mapping was performed in 23 Langendorff perfused rabbit ventricles with atrioventricular block and either right ventricular (RV) or left ventricular (LV) pacing during normokalemia or hypokalemia. Apamin prolonged the action potential duration (APD) measured to 80% repolarization (APD80) by 26 ms [95% confidence interval, CI, 14–37] during normokalemia and by 54 ms [CI, 40 to 68] during hypokalemia (P=0.01) at 1000 ms pacing cycle length (PCL). In hypokalemic ventricles, apamin increased the maximal slope of APD restitution, the PCL threshold of APD alternans, the PCL for wavebreak induction and the area of spatially discordant APD alternans. Apamin significantly facilitated the induction of sustained VF (from 3/9 hearts to 9/9 hearts, P=0.009). Short term cardiac memory was assessed by the slope of APD80 versus activation time. The slope increased from 0.01 [CI, −0.09 to 0.12] at baseline to 0.34 [CI, 0.23 to 0.44] after apamin (P<0.001) during RV pacing, and from 0.07 [CI, −0.05 to 0.20] to 0.54 [CI, 0.06 to 1.03] after apamin infusion (P=0.045) during LV pacing. Patch-clamp studies confirmed increased IKASin isolated rabbit ventricular myocytes during hypokalemia (P=0.038). Conclusions Hypokalemia activates IKAS to shorten APD and maintain repolarization reserve at late activation sites during ventricular pacing. IKAS blockade prominently lengthens the APD at late activation sites and facilitates VF induction. PMID:26362634

  5. Cell specific dopamine modulation of the transient potassium current in the pyloric network by the canonical D1 receptor signal transduction cascade.

    PubMed

    Zhang, Hongmei; Rodgers, Edmund W; Krenz, Wulf-Dieter C; Clark, Merry C; Baro, Deborah J

    2010-08-01

    Dopamine (DA) modifies the motor pattern generated by the pyloric network in the stomatogastric ganglion (STG) of the spiny lobster, Panulirus interruptus, by directly acting on each of the circuit neurons. The 14 pyloric neurons fall into six cell types, and DA actions are cell type specific. The transient potassium current mediated by shal channels (I(A)) is a common target of DA modulation in most cell types. DA shifts the voltage dependence of I(A) in opposing directions in pyloric dilator (PD) versus lateral pyloric (LP) neurons. The mechanism(s) underpinning cell-type specific DA modulation of I(A) is unknown. DA receptors (DARs) can be classified as type 1 (D1R) or type 2 (D2R). D1Rs and D2Rs are known to increase and decrease intracellular cAMP concentrations, respectively. We hypothesized that the opposing DA effects on PD and LP I(A) were due to differences in DAR expression patterns. In the present study, we found that LP expressed somatodendritic D1Rs that were concentrated near synapses but did not express D2Rs. Consistently, DA modulation of LP I(A) was mediated by a Gs-adenylyl cyclase-cAMP-protein kinase A pathway. Additionally, we defined antagonists for lobster D1Rs (flupenthixol) and D2Rs (metoclopramide) in a heterologous expression system and showed that DA modulation of LP I(A) was blocked by flupenthixol but not by metoclopramide. We previously showed that PD neurons express D2Rs, but not D1Rs, thus supporting the idea that cell specific effects of DA on I(A) are due to differences in receptor expression.

  6. Shared requirement for dynein function and intact microtubule cytoskeleton for normal surface expression of cardiac potassium channels.

    PubMed

    Loewen, Matthew E; Wang, Zhuren; Eldstrom, Jodene; Dehghani Zadeh, Alireza; Khurana, Anu; Steele, David F; Fedida, David

    2009-01-01

    Potassium channels at the cardiomyocyte surface must eventually be internalized and degraded, and changes in cardiac potassium channel expression are known to occur during myocardial disease. It is not known which trafficking pathways are involved in the control of cardiac potassium channel surface expression, and it is not clear whether all cardiac potassium channels follow a common pathway or many pathways. In the present study we have surveyed the role of retrograde microtubule-dependent transport in modulating the surface expression of several cardiac potassium channels in ventricular myocytes and heterologous cells. The disruption of microtubule transport in rat ventricular myocytes with nocodazole resulted in significant changes in potassium currents. A-type currents were enhanced 1.6-fold at +90 mV, rising from control densities of 20.9 +/- 2.8 to 34.0 +/- 5.4 pA/pF in the nocodazole-treated cells, whereas inward rectifier currents were reduced by one-third, perhaps due to a higher nocodazole sensitivity of Kir channel forward trafficking. These changes in potassium currents were associated with a significant decrease in action potential duration. When expressed in heterologous human embryonic kidney (HEK-293) cells, surface expression of Kv4.2, known to substantially underlie A-type currents in rat myocytes, was increased by nocodazole, by the dynein inhibitor erythro-9-(2-hydroxy-3-nonyl) adenine hydrochloride, and by p50 overexpression, which specifically interferes with dynein motor function. Peak current density was 360 +/- 61.0 pA/pF in control cells and 658 +/- 94.5 pA/pF in cells overexpressing p50. The expression levels of Kv2.1, Kv3.1, human ether-a-go-go-related gene, and Kir2.1 were similarly increased by p50 overexpression in this system. Thus the regulation of potassium channel expression involves a common dynein-dependent process operating similarly on the various channels.

  7. Characterization of Voltage-Gated Potassium Channels in Human Neural Progenitor Cells

    PubMed Central

    Schaarschmidt, Grit; Wegner, Florian; Schwarz, Sigrid C.; Schmidt, Hartmut; Schwarz, Johannes

    2009-01-01

    Background Voltage-gated potassium (Kv) channels are among the earliest ion channels to appear during brain development, suggesting a functional requirement for progenitor cell proliferation and/or differentiation. We tested this hypothesis, using human neural progenitor cells (hNPCs) as a model system. Methodology/Principal Findings In proliferating hNPCs a broad spectrum of Kv channel subtypes was identified using quantitative real-time PCR with a predominant expression of the A-type channel Kv4.2. In whole-cell patch-clamp recordings Kv currents were separated into a large transient component characteristic for fast-inactivating A-type potassium channels (IA) and a small, sustained component produced by delayed-rectifying channels (IK). During differentiation the expression of IA as well as A-type channel transcripts dramatically decreased, while IK producing delayed-rectifiers were upregulated. Both Kv currents were differentially inhibited by selective neurotoxins like phrixotoxin-1 and α-dendrotoxin as well as by antagonists like 4-aminopyridine, ammoniumchloride, tetraethylammonium chloride and quinidine. In viability and proliferation assays chronic inhibition of the A-type currents severely disturbed the cell cycle and precluded proper hNPC proliferation, while the blockade of delayed-rectifiers by α-dendrotoxin increased proliferation. Conclusions/Significance These findings suggest that A-type potassium currents are essential for proper proliferation of immature multipotent hNPCs. PMID:19584922

  8. BmTx3, a scorpion toxin with two putative functional faces separately active on A-type K+ and HERG currents.

    PubMed Central

    Huys, Isabelle; Xu, Chen-Qi; Wang, Cheng-Zhong; Vacher, Hélène; Martin-Eauclaire, Marie-France; Chi, Cheng-Wu; Tytgat, Jan

    2004-01-01

    A novel HERG channel blocker was isolated from the venom of the scorpion Buthus martensi Karsch, sequenced and characterized at the pharmacological level after chemical synthesis. According to the determined amino acid sequence, the cDNA and genomic genes were then cloned. The genomic gene consists of two exons interrupted by an intron of 65 bp at position -6 upstream from the mature toxin. The protein sequence of this toxin was completely identical with that of a known A-type K+ current blocker BmTx3, belonging to scorpion alpha-KTx subfamily 15. Thus BmTx3 is the first reported alpha-KTx peptide also showing HERG-blocking activity, like gamma-KTx peptides. Moreover, different from classical alpha-KTx peptides, such as charybdotoxin, BmTx3 cannot block Shaker -type K+ channels. Phylogenetic tree analysis reveals that this toxin takes an intermediate position between classical alpha-KTx and gamma-KTx toxins. From a structural point of view, we propose that two separate functional faces might exist on the BmTx3 molecule, responsible for the two different K+-current-blocking functions. Face A, composed of Arg18 and Lys19 in the alpha-helix side, might correspond to HERG blocking activity, whereas Face B, containing a putative functional dyad (Lys27 and Tyr36) in the beta-sheet side, might correspond to A-type blocking activity. A specific deletion mutant with the disrupted Face B, BmTx3-Y36P37del, loses the A-type current-blocking activity, but keeps a similar HERG-blocking activity, as seen with the wild-type toxin. PMID:14599291

  9. Intraneuronal Aβ accumulation induces hippocampal neuron hyperexcitability through A-type K(+) current inhibition mediated by activation of caspases and GSK-3.

    PubMed

    Scala, Federico; Fusco, Salvatore; Ripoli, Cristian; Piacentini, Roberto; Li Puma, Domenica Donatella; Spinelli, Matteo; Laezza, Fernanda; Grassi, Claudio; D'Ascenzo, Marcello

    2015-02-01

    Amyloid β-protein (Aβ) pathologies have been linked to dysfunction of excitability in neurons of the hippocampal circuit, but the molecular mechanisms underlying this process are still poorly understood. Here, we applied whole-cell patch-clamp electrophysiology to primary hippocampal neurons and show that intracellular Aβ42 delivery leads to increased spike discharge and action potential broadening through downregulation of A-type K(+) currents. Pharmacologic studies showed that caspases and glycogen synthase kinase 3 (GSK-3) activation are required for these Aβ42-induced effects. Extracellular perfusion and subsequent internalization of Aβ42 increase spike discharge and promote GSK-3-dependent phosphorylation of the Kv4.2 α-subunit, a molecular determinant of A-type K(+) currents, at Ser-616. In acute hippocampal slices derived from an adult triple-transgenic Alzheimer's mouse model, characterized by endogenous intracellular accumulation of Aβ42, CA1 pyramidal neurons exhibit hyperexcitability accompanied by increased phosphorylation of Kv4.2 at Ser-616. Collectively, these data suggest that intraneuronal Aβ42 accumulation leads to an intracellular cascade culminating into caspases activation and GSK-3-dependent phosphorylation of Kv4.2 channels. These findings provide new insights into the toxic mechanisms triggered by intracellular Aβ42 and offer potentially new therapeutic targets for Alzheimer's disease treatment.

  10. Intraneuronal Aβ accumulation induces hippocampal neuron hyperexcitability through A-type K+ current inhibition mediated by activation of caspases and GSK-3

    PubMed Central

    Scala, Federico; Fusco, Salvatore; Ripoli, Cristian; Piacentini, Roberto; Li Puma, Domenica Donatella; Spinelli, Matteo; Laezza, Fernanda; Grassi, Claudio; D’Ascenzo, Marcello

    2016-01-01

    Amyloid β-protein (Aβ) pathologies have been linked to dysfunction of excitability in neurons of the hippocampal circuit, but the molecular mechanisms underlying this process are still poorly understood. Here, we applied whole-cell patch-clamp electrophysiology to primary hippocampal neurons and show that intracellular Aβ42 delivery leads to increased spike discharge and action potential broadening through downregulation of A-type K+ currents. Pharmacologic studies showed that caspases and glycogen synthase kinase 3 (GSK-3) activation are required for these Aβ42-induced effects. Extracellular perfusion and subsequent internalization of Aβ42 increase spike discharge and promote GSK-3-dependent phosphorylation of the Kv4.2 α-subunit, a molecular determinant of A-type K+ currents, at Ser-616. In acute hippocampal slices derived from an adult triple-transgenic Alzheimer’s mouse model, characterized by endogenous intracellular accumulation of Aβ42, CA1 pyramidal neurons exhibit hyperexcitability accompanied by increased phosphorylation of Kv4.2 at Ser-616. Collectively, these data suggest that intraneuronal Aβ42 accumulation leads to an intracellular cascade culminating into caspases activation and GSK-3-dependent phosphorylation of Kv4.2 channels. These findings provide new insights into the toxic mechanisms triggered by intracellular Aβ42 and offer potentially new therapeutic targets for Alzheimer’s disease treatment. PMID:25541422

  11. Enhanced excitability and suppression of A-type K+ currents in joint sensory neurons in a murine model of antigen-induced arthritis

    PubMed Central

    Qu, Lintao; Caterina, Michael J.

    2016-01-01

    Pain is a dominant symptom of rheumatoid arthritis (RA) and its adequate treatment represents a major unmet need. However, the cellular mechanisms that drive arthritis pain are largely unexplored. Here, we examined the changes in the activity of joint sensory neurons and the associated ionic mechanisms using an animal model of antigen-induced arthritis (AIA). Methylated-bovine serum albumin (mBSA), but not vehicle challenge, in the ankle of previously immunized mice produced time-dependent symptoms of arthritis, including joint inflammation, primary mechanical hyperalgesia in the ipsilateral ankle, and secondary mechanical and heat hyperalgesia in the ipsilateral hindpaw. In vivo electrophysiological recordings revealed that Dil-labeled joint sensory neurons in AIA mice exhibited a greater incidence of spontaneous activity, mechanically evoked after-discharges, and/or increased responses to mechanical stimulation of their receptive fields, compared to control animals. Whole-cell recordings in vitro showed that AIA enhanced the excitability of joint sensory neurons. These signs of neuronal hyperexcitability were associated with a significant reduction in the density of A-type K+ currents. Thus, our data suggest that neuronal hyperexcitability, brought about in part by reduced A-type K+ currents, may contribute to pain-related behaviors that accompany antigen-induced arthritis and/or other antigen-mediated diseases. PMID:27363579

  12. Ionic channel function in action potential generation: current perspective.

    PubMed

    Baranauskas, Gytis

    2007-04-01

    Over 50 years ago, Hodgkin and Huxley laid down the foundations of our current understanding of ionic channels. An impressive progress has been made during the following years that culminated in the revelation of the details of potassium channel structure. Nevertheless, even today, we cannot separate well currents recorded in central mammalian neurons. Many modern concepts about the function of sodium and potassium currents are based on experiments performed in nonmammalian cells. The recent recognition of the fast delayed rectifier current indicates that we need to reevaluate the biophysical role of sodium and potassium currents. This review will consider high quality voltage clamp data obtained from the soma of central mammalian neurons in the view of our current knowledge about proteins forming ionic channels. Fast sodium currents and three types of outward potassium currents, the delayed rectifier, the subthreshold A-type, and the D-type potassium currents, are discussed here. An updated current classification with biophysical role of each current subtype is provided. This review shows that details of kinetics of both sodium and outward potassium currents differ significantly from the classical descriptions and these differences may be of functional significance.

  13. Rapid component I(Kr) of cardiac delayed rectifier potassium currents in guinea-pig is inhibited by alpha(1)-adrenoreceptor activation via protein kinase A and protein kinase C-dependent pathways.

    PubMed

    Wang, Sen; Xu, Dong-Jie; Cai, Jing-Bo; Huang, Yuan-Zhu; Zou, Jian-Gang; Cao, Ke-Jiang

    2009-04-17

    Ventricular tachyarrhythmias are often precipitated by physical or emotional stress, indicating a link between increased adrenergic stimulation and cardiac ion channel activity. Human ether-a-go-go related gene (hERG) potassium channels conduct the rapid component of delayed rectifier potassium current, I(kr), a crucial component for action potential repolarization. To evaluate the correlation between increased alpha(1)-adrenergic activity and the rapid component of cardiac I(kr), whole-cell patch-clamp recording was performed in isolated guinea-pig ventricular myocytes. Stimulation of alpha(1)-adrenoceptors using phenylephrine (0.1 nM-100 microM) reduced I(kr) current in a dose-dependent manner at 37 degrees C. Phenylephrine (0.1 microM) reduced I(kr) current to 66.83+/-3.16%. Chelerythrine (1 microM), a specific inhibitor of protein kinase C (PKC) completely inhibited the changes in I(kr) trigged by 0.1 microM phenylephrine. KT5720 (2.5 microM), a specific inhibitor of protein kinase A (PKA) partially inhibited the current decrease induced by 0.1 microM phenylephrine. Both chelerythrine and KT5720 drastically reduced the phenylephrine-induced effects, indicating possible involvement of PKC and PKA in the alpha(1)-adrenergic inhibition of I(kr). Our data suggest a link between I(kr) and the alpha(1)-adrenoceptor, involving activation of PKC and PKA in arrhythmogenesis.

  14. Low Potassium (Hypokalemia)

    MedlinePlus

    ... can be life-threatening and requires urgent medical attention. Low potassium (hypokalemia) has many causes. The most common cause is excessive potassium loss in urine due to prescription medications that increase urination. Also ...

  15. Potassium: more beneficial effects.

    PubMed

    He, F J; MacGregor, G A

    2003-10-01

    Over 70 years ago, potassium was found to have a natriuretic effect and was used in patients with heart failure. However, it took many years for its role in the control of blood pressure to be recognized. Recently, epidemiological and clinical studies in man and experimental studies in animals have shown that increasing potassium intake towers blood pressure and that communities with a high potassium intake tend to have lower population blood pressures. Several studies have shown an interaction between salt intake and potassium intake. However, the recent DASH-Sodium (Dietary Approaches to Stop Hypertension) study demonstrates an additive effect of a low salt and high potassium diet on blood pressure. Increasing potassium intake may have other beneficial effects, for example, reducing the risk of stroke and preventing the development of renal disease independent of its effect on blood pressure. A high potassium intake reduces calcium excretion and could play an important role in the management of hypercalciuria and kidney stone formation, as well as bone demineralization. Potassium intake may also play an important role in carbohydrate intolerance. A reduced serum potassium increases the risk of lethal ventricular arrhythmias in those at risk, i.e. patients with ischemic heart disease, heart failure or left ventricular hypertrophy, and increasing potassium intake may prevent this. In this article, we address the evidence for the important role of potassium intake in regulating blood pressure and other beneficial effects of potassium which may be independent of and additional to its effect on blood pressure.

  16. Derangements of potassium.

    PubMed

    Medford-Davis, Laura; Rafique, Zubaid

    2014-05-01

    Changes in potassium elimination, primarily due to the renal and GI systems, and shifting potassium between the intracellular and extracellular spaces cause potassium derangement. Symptoms are vague, but can be cardiac, musculoskeletal, or gastrointestinal. There are no absolute guidelines for when to treat, but it is generally recommended when the patient is symptomatic or has ECG changes. Treatment of hyperkalemia includes cardiac membrane stabilization with IV calcium, insulin and beta-antagonists to push potassium intracellularly, and dialysis. Neither sodium bicarbonate nor kayexelate are recommended. Treatment of symptomatic hypokalemia consists of PO or IV repletion with potassium chloride and magnesium sulfate.

  17. Contributions of Kv7-mediated potassium current to sub- and suprathreshold responses of rat layer II/III neocortical pyramidal neurons

    PubMed Central

    Guan, D.; Higgs, M. H.; Horton, L. R.; Spain, W. J.

    2011-01-01

    After block of Kv1- and Kv2-mediated K+ currents in acutely dissociated neocortical pyramidal neurons from layers II/III of rat somatosensory and motor cortex, the remaining current is slowly activating and persistent. We used whole cell voltage clamp to show that the Kv7 blockers linopirdine and XE-991 blocked a current with similar kinetics to the current remaining after combined block of Kv1 and Kv2 channels. This current was sensitive to low doses of linopirdine and activated more slowly and at more negative potentials than Kv1- or Kv2-mediated current. The Kv7-mediated current decreased in amplitude with time in whole cell recordings, but in most cells the current was stable for several minutes. Current in response to a traditional M-current protocol was blocked by muscarine, linopirdine, and XE-991. Whole cell slice recordings revealed that the Q10 for channel deactivation was ∼2.5. Sharp electrode current-clamp recordings from adult pyramidal cells demonstrated that block of Kv7-mediated current with XE-991 reduced rheobase, shortened the latency to firing to near rheobase current, induced more regular firing at low current intensity, and increased the rate of firing to a given current injection. XE-991 did not affect single action potentials or spike frequency adaptation. Application of XE-991 also eliminated subthreshold voltage oscillations and increased gain for low-frequency inputs (<10 Hz) without affecting gain for higher frequency inputs. These data suggest important roles for Kv7 channels in subthreshold regulation of excitability, generation of theta-frequency subthreshold oscillations, regulation of interspike intervals, and biasing selectivity toward higher frequency inputs. PMID:21697446

  18. Blockade of the inward rectifier potassium current by the Ca(2+)-ATPase inhibitor 2',5'-di(tert-butyl)-1,4-benzohydroquinone (BHQ).

    PubMed Central

    Hasséssian, H.; Vaca, L.; Kunze, D. L.

    1994-01-01

    1. We have investigated the effect of 2',5'-di (tert-butyl)-1,4-benzohydroquinone (BHQ) and thapsigargin, inhibitors of the intracellular Ca(2+)-ATPase, on ionic currents in rat basophilic leukaemia (RBL-2H3) cells under whole cell voltage clamp. 2. The whole cell current was inwardly rectifying and reversed at -35 +/- 6 mV (n = 16). The conductance of the inward current increased as the concentration of extracellular K+ was raised from 2.7 to 5.4, 10.8 and 21.6 mM. BaCl2 (100 microM) reduced the current to a small linear component and shifted the reversal potential to -4 +/- 3 mV (n = 6). A concentration of 50 microM BaCl2 produced 45 +/- 10% (n = 4) blockade of the inward current. 3. BHQ and thapsigargin were examined for their effects on the inwardly rectifying current. A maximal blockade of inward current was obtained within 6 min after perfusion with 10 microM BHQ. The small current remaining after blockade with BHQ had a linear voltage-dependence and reversed direction at -6 +/- 9 mV (n = 6). Thapsigargin (up to 3 microM) was without effect on the inward rectifier. 4. In contrast to the blockade of the inward rectifier produced by BaCl2 which was predominantly on the steady state current, particularly at the very hyperpolarized holding potentials (-120 mV), blockade by BHQ was equally strong on the instantaneous as well as the steady state current. 5. Blockade of the inward rectifier by BHQ may cause depolarization of the cell which will affect Ca2+ influx during investigations with BHQ.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7952872

  19. Penicillin V Potassium Oral

    MedlinePlus

    Penicillin V potassium is an antibiotic used to treat certain infections caused by bacteria such as pneumonia, scarlet fever, and ear, ... Penicillin V potassium comes as a tablet and liquid to take by mouth. It is usually taken every 6 hours (four ...

  20. Potassium food supplement

    NASA Technical Reports Server (NTRS)

    Bourland, C. T.; Huber, C. S.; Rambaut, C.; Heidelbaugh, N. D.

    1973-01-01

    Potassium gluconate is considered best supplementary source for potassium. Gluconate consistently received highest taste rating and was indistinguishable from nonsupplemented samples. No unfavorable side effects were found during use, and none are reported in literature. Gluconate is normal intermediary metabolite that is readily adsorbed and produces no evidence of gastrointestinal ulcerations.

  1. Development of potassium ion conducting hollow glass fibers. [potassium sulfur battery

    NASA Technical Reports Server (NTRS)

    Tsang, F. Y.

    1974-01-01

    Potassium ion conducting glasses, chemically resistant to potassium, potassium sulfide and sulfur, were made and their possible utility as the membrane material for a potassium/sulfur battery was evaluated. At least one satisfactory candidate was found. It possesses an electrical resistance which makes it usable as a membrane in the form of a fine hollow fiber. It's chemical and electrochemical resistances are excellent. The other aspects of the possible potassium sulfur battery utilizing such fine hollow fibers, including the header (or tube sheet) and a cathode current collector were studied. Several cathode materials were found to be satisfactory. None of the tube sheet materials studied possessed all the desired properties. Multi-fiber cells had very limited life-time due to physical failure of fibers at the fiber/tube sheet junctions.

  2. The synergistic inhibitory actions of oxcarbazepine on voltage-gated sodium and potassium currents in differentiated NG108-15 neuronal cells and model neurons.

    PubMed

    Huang, Chin-Wei; Huang, Chao-Ching; Lin, Ming-Wei; Tsai, Jing-Jane; Wu, Sheng-Nan

    2008-08-01

    Oxcarbazepine (OXC), one of the newer anti-epileptic drugs, has been demonstrating its efficacy on wide-spectrum neuropsychiatric disorders. However, the ionic mechanism of OXC actions in neurons remains incompletely understood. With the aid of patch-clamp technology, we first investigated the effects of OXC on ion currents in NG108-15 neuronal cells differentiated with cyclic AMP. We found OXC (0.3-30 microm) caused a reversible reduction in the amplitude of voltage-gated Na+ current (INa). The IC50 value required for the inhibition of INa by OXC was 3.1 microm. OXC (3 microm) could shift the steady-state inactivation of INa to a more negative membrane potential by approximately -9 mV with no effect on the slope of the inactivation curve, and produce a significant prolongation in the recovery of INa inactivation. Additionally, OXC was effective in suppressing persistent INa (INa(P)) elicited by long ramp pulses. The blockade of INa by OXC does not simply reduce current magnitude, but alters current kinetics. Moreover, OXC could suppress the amplitude of delayed rectifier K+ current (IK(DR)), with no effect on M-type K+ current (IK(M)). In current-clamp configuration, OXC could reduce the amplitude of action potentials and prolong action-potential duration. Furthermore, the simulations, based on hippocampal pyramidal neurons (Pinsky-Rinzel model) and a network of the Hodgkin-Huxley model, were analysed to investigate the effect of OXC on action potentials. Taken together, our results suggest that the synergistic blocking effects on INa and IK(DR) may contribute to the underlying mechanisms through which OXC affects neuronal function in vivo.

  3. 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

    Wester, Jason C; Contreras, Diego

    2013-08-01

    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⁺ nactivation 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.

  4. Electrocardiographic method for identifying drug-induced repolarization abnormalities associated with a reduction of the rapidly activating delayed rectifier potassium current.

    PubMed

    Couderc, J P; Vaglio, M; Xia, X; McNitt, S; Hyrien, O

    2006-01-01

    Several important non-cardiac drugs have been removed from the market after revealing harmful effect that was not identified during prior safety-assessment studies. We developed a new technique for the measurements of repolarization abnormalities from surface ECGs; this method improves sensitivity and specificity of the current technique used to identify the presence of abnormal ion current kinetics in the myocardial cells namely a prolongation of the QT interval on the surface ECG signal. We described in this paper the method and preliminary results, revealing the superiority of our technique that may play a role in the future of drug-safety assessment.

  5. Potassium targets from KI

    NASA Astrophysics Data System (ADS)

    Sletten, G.

    1982-09-01

    Targets of potassium iodide (KI) on thin carbon backings have been prepared. Potassium isotopes are supplied as chlorides, and the chlorine is, in certain experiments, an unwanted contaminant. Target peeparation involves conversion of KCl to KI and subsequent vacuum evaporation of the iodide. Targets of both 39K and 41K in the thickness range of 60 to 100 μg/cm 2 of potassium have been prepared. These targets contain less than 0.5 μg/cm 2 of chlorine impurity and are stable in α-beams of 25 MeV.

  6. Evidence for a modulatory effect of external potassium ions on ionic current mediated by the cardiac Na+-Ca2+ exchanger.

    PubMed

    Zhang, Y H; Hancox, J C

    2003-01-01

    The aim of this study was to investigate whether or not the activity of the cardiac Na(+)-Ca(2+) exchanger might be directly sensitive to external K(+) concentration ([K(+)](e)). Measurements of whole-cell exchanger current (I(NaCa)) were made at 37 degrees C from guinea-pig isolated ventricular myocytes, using whole-cell patch clamp recording with major interfering conductances blocked. Changing [K(+)](e) from 0 to 5mM significantly reduced both outward and inward exchange currents in a time-dependent manner. Various [K(+)](e) between 1 and 15 mM were tested and the inhibitory effect was observed to be concentration-dependent. At steady-state, 5mM [K(+)](e) decreased the density of Ni(2+)-sensitive current by 52.8+/-4.3% (mean+/-S.E.M., n=6) and of 0Na0Ca-sensitive current by 39.0+/-4.4% (n=5). The possibility that the inhibitory effect of external K(+) on I(NaCa) might wholly or in part be secondary to activation of the sarcolemmal Na(+)-K(+) pump was investigated by testing the effect of K(+) addition in the presence of a high concentration of strophanthidin (500 microM). Ni(2+)-sensitive I(NaCa) was still observed to be sensitive to external K(+) (I(NaCa) decreased by 39.4+/-9.4%, n=4), suggesting that the inhibitory effect could occur independently of activation of the Na(+)-K(+) pump. The effect of external K(+) on I(NaCa) was verified using a baby hamster kidney (BHK) cell line stably expressing the cardiac Na(+)-Ca(2+) exchanger isoform, NCX1. Similar to native I(NaCa), NCX1 current was also suppressed by [K(+)](e). However, [K(+)](e) did not alter current amplitude in untransfected BHK cells. The effect of [K(+)](e) on I(NaCa) could not be attributed to simply adding any monovalent cation back to the external solution, since it was not reproduced by application of equimolar Li(+), Cs(+) and TEA(+). Rb(+), however, could mimic the effect of K(+). Collectively, these data suggest that external K(+) at physiologically and pathologically relevant

  7. Mechanisms of action of antiarrhythmic agent bertosamil on hKv1.5 channels and outward potassium current in human atrial myocytes.

    PubMed

    Godreau, David; Vranckx, Roger; Hatem, Stéphane N

    2002-02-01

    We analyzed the mechanism of action of the antiarrhythmic agent bertosamil on hKv1.5 channels expressed in Chinese hamster ovary cells (I(hKv1.5)) and on the outward current (I(o)) of human atrial myocytes (HAMs) by using the whole cell patch-clamp technique to record current. External application of 10 microM bertosamil inhibited I(hKv1.5), accelerated its time-dependent decay, and slowed its deactivation. When bertosamil was applied at rest or intracellularly (50 microM), it accelerated the rate of I(hKv1.5) inactivation without change of the peak amplitude. At the steady-state effect of intracellular bertosamil, external drug application only inhibited I(hKv1.5). When cesium was the charge carrier, bertosamil inhibited I(hKv1.5) but had no effect on its time course. Intracellular tetraethylammonium inhibited I(hKv1.5), suppressed its inactivation, and prevented bertosamil effects. Bertosamil-treated I(hKv1.5) became highly sensitive to the rate of membrane stimulation and to cumulative inactivation phenomenon. In HAMs, bertosamil also increased the rate and extent of I(o) inactivation and slowed its recovery from inactivation, whereas after drug application I(o) became highly sensitive to cumulative inactivation phenomenon. In conclusion, bertosamil 1) causes a use-dependent inhibition of the current upon external drug application, and 2) accelerates the rate of current inactivation when applied at rest or intracellularly. These effects result from both an open-channel block and acceleration of the rate of channel inactivation and contribute to the modulation by bertosamil of I(o) in HAM.

  8. Potassium carbonate poisoning

    MedlinePlus

    ... is a white powder used to make soap, glass, and other items. This article discusses poisoning from ... Potassium carbonate is found in: Glass Some dishwasher soaps Some ... that is used in fertilizers) Some home permanent-wave solutions ...

  9. Low potassium level

    MedlinePlus

    ... laxative, which can cause diarrhea Chronic kidney disease Diuretic medicines (water pills), used to treat heart failure ... potassium through a vein (IV). If you need diuretics, your provider may: Switch you to a form ...

  10. Kv7.5 Potassium Channel Subunits Are the Primary Targets for PKA-Dependent Enhancement of Vascular Smooth Muscle Kv7 Currents

    PubMed Central

    Mani, Bharath K.; Robakowski, Christina; Brueggemann, Lyubov I.; Cribbs, Leanne L.; Tripathi, Abhishek; Majetschak, Matthias

    2016-01-01

    Kv7 (KCNQ) channels, formed as homo- or heterotetramers of Kv7.4 and Kv7.5 α-subunits, are important regulators of vascular smooth muscle cell (VSMC) membrane voltage. Recent studies demonstrate that direct pharmacological modulation of VSMC Kv7 channel activity can influence blood vessel contractility and diameter. However, the physiologic regulation of Kv7 channel activity is still poorly understood. Here, we study the effect of cAMP/protein kinase A (PKA) activation on whole cell K+ currents through endogenous Kv7.5 channels in A7r5 rat aortic smooth muscle cells or through Kv7.4/Kv7.5 heteromeric channels natively expressed in rat mesenteric artery smooth muscle cells. The contributions of specific α-subunits are further dissected using exogenously expressed human Kv7.4 and Kv7.5 homo- or heterotetrameric channels in A7r5 cells. Stimulation of Gαs-coupled β-adrenergic receptors with isoproterenol induced PKA-dependent activation of endogenous Kv7.5 currents in A7r5 cells. The receptor-mediated enhancement of Kv7.5 currents was mimicked by pharmacological agents that increase [cAMP] (forskolin, rolipram, 3-isobutyl-1-methylxanthine, and papaverine) or mimic cAMP (8-bromo-cAMP); the 2- to 4-fold PKA-dependent enhancement of currents was also observed with exogenously expressed Kv7.5 channels. In contrast, exogenously-expressed heterotetrameric Kv7.4/7.5 channels in A7r5 cells or native mesenteric artery smooth muscle Kv7.4/7.5 channels were only modestly enhanced, and homo-tetrameric Kv7.4 channels were insensitive to this regulatory pathway. Correspondingly, proximity ligation assays indicated that isoproterenol induced PKA-dependent phosphorylation of exogenously expressed Kv7.5 channel subunits, but not of Kv7.4 subunits. These results suggest that signal transduction-mediated responsiveness of vascular smooth muscle Kv7 channel subunits to cAMP/PKA activation follows the order of Kv7.5 >> Kv7.4/Kv7.5 > Kv7.4. PMID:26700561

  11. Inflammation enhanced brain-derived neurotrophic factor-induced suppression of the voltage-gated potassium currents in small-diameter trigeminal ganglion neurons projecting to the trigeminal nucleus interpolaris/caudalis transition zone.

    PubMed

    Takeda, M; Takahashi, M; Matsumoto, S

    2014-03-07

    We recently indicated that brain-derived neurotrophic factor (BDNF) enhances the excitability of small-diameter trigeminal ganglion (TRG) neurons projecting onto the trigeminal nucleus interpolaris/caudalis (Vi/Vc) transition zone via a paracrine mechanism following masetter muscle (MM) inflammation. The present study investigated whether modulation of voltage-gated potassium (K) channels by BDNF contributes to this hyperexcitability effect. To induce inflammation we injected complete Freund's adjuvant (CFA) into the MM. The escape threshold from mechanical stimulation applied to skin above the inflamed MM was significantly lower than in naïve rats. TRG neurons innervating the site of inflammation were subsequently identified by fluorogold (FG) labeling, and microbeads (MB) were used to label neurons projecting specifically to the Vi/Vc region. BDNF significantly decreased the total, transient (IA), and sustained (IK) currents in FG-/MB-labeled small-diameter TRG neurons under voltage-clamp conditions in naïve and inflamed rats. The magnitude of inhibition of IA and IK currents by BDNF in FG-/MB-labeled TRG neurons was significantly greater in inflamed rats than in naïve rats, and BDNF inhibited IA to a significantly greater extent than IK. Furthermore, co-administration of K252a, a tyrosine kinase inhibitor, abolished the suppression of IA and IK currents by BDNF. These results suggested that the inhibitory effects of BDNF on IA and IK currents in small-diameter TRG neurons projecting onto the Vi/Vc potentiate neuronal excitability, and in turn, contribute to MM inflammatory hyperalgesia. These findings support the development of voltage-gated K(+) channel openers and tyrosine kinase inhibitors as potential therapeutic agents for the treatment of trigeminal inflammatory hyperalgesia. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  12. Effects of extracellular potassium diffusion on electrically coupled neuron networks

    NASA Astrophysics Data System (ADS)

    Wu, Xing-Xing; Shuai, Jianwei

    2015-02-01

    Potassium accumulation and diffusion during neuronal epileptiform activity have been observed experimentally, and potassium lateral diffusion has been suggested to play an important role in nonsynaptic neuron networks. We adopt a hippocampal CA1 pyramidal neuron network in a zero-calcium condition to better understand the influence of extracellular potassium dynamics on the stimulus-induced activity. The potassium concentration in the interstitial space for each neuron is regulated by potassium currents, Na+-K+ pumps, glial buffering, and ion diffusion. In addition to potassium diffusion, nearby neurons are also coupled through gap junctions. Our results reveal that the latency of the first spike responding to stimulus monotonically decreases with increasing gap-junction conductance but is insensitive to potassium diffusive coupling. The duration of network oscillations shows a bell-like shape with increasing potassium diffusive coupling at weak gap-junction coupling. For modest electrical coupling, there is an optimal K+ diffusion strength, at which the flow of potassium ions among the network neurons appropriately modulates interstitial potassium concentrations in a degree that provides the most favorable environment for the generation and continuance of the action potential waves in the network.

  13. Dietary patterns extracted from the current Japanese diet and their associations with sodium and potassium intakes estimated by repeated 24 h urine collection.

    PubMed

    Fujiwara, Aya; Asakura, Keiko; Uechi, Ken; Masayasu, Shizuko; Sasaki, Satoshi

    2016-10-01

    To identify dietary patterns in the current Japanese diet and evaluate the associations between these patterns and Na and K intakes. Dietary patterns were extracted by factor analysis from the intakes of food groups assessed with a validated self-administrated diet history questionnaire. Na and K intakes and urinary Na:K were assessed by repeated 24 h urine collection. Healthy Japanese adults aged 20-69 years (353 men and 349 women). Twenty study areas in twenty-three prefectures in Japan. Result Four dietary patterns were identified in each sex. After adjustment for several confounding factors, the 'Fish and vegetable' pattern was associated with higher urinary Na excretion, but the association was not significant (P=0·37 in men and P=0·06 in women). This pattern was also associated with higher K excretion in both sexes. The 'Noodle' pattern tended to be associated with higher urinary Na excretion (P=0·17 in men and P=0·04 in women) and higher Na:K (P=0·02 in men). The 'Meat, vegetable and oil' (in men)/'Meat and oil' (in women) and 'Bread and confectioneries' patterns were not associated with urinary Na excretion (in men) or were negatively associated (in women). Contrary to the case in Western countries, the 'Fish and vegetable' and 'Noodle' patterns contributed to higher Na intake in Japan. Target foods for salt reduction should be set based on careful consideration of the relationships between dietary patterns and Na and K intakes in the target population.

  14. Elevated potassium elicits recurrent surges of large GABAA-receptor-mediated post-synaptic currents in hippocampal CA3 pyramidal neurons.

    PubMed

    Shin, Damian Seung-Ho; Yu, Wilson; Sutton, Alex; Calos, Megan; Carlen, Peter Louis

    2011-03-01

    Previously, we found that rat hippocampal CA3 interneurons become hyperactive with increasing concentrations of extracellular K(+) up to 10 mM. However, it is unclear how this enhanced interneuronal activity affects pyramidal neurons. Here we voltage-clamped rat hippocampal CA3 pyramidal neurons in vitro at 0 mV to isolate γ-aminobutyric acid (GABA)-activated inhibitory post-synaptic currents (IPSCs) and measured these in artificial cerebrospinal fluid (aCSF) and with 10 mM K(+) bath perfusion. In aCSF, small IPSCs were present with amplitudes of 0.053 ± 0.007 nA and a frequency of 0.27 ± 0.14 Hz. With 10 mM K(+) perfusion, IPSCs increased greatly in frequency and amplitude, culminating in surge events with peak amplitudes of 0.56 ± 0.08 nA, that appeared and disappeared cyclically with durations lasting 2.02 ± 0.37 min repeatedly, up to 10 times over a 30-min bath perfusion of elevated K(+). These large IPSCs were GABA(A)-receptor mediated and did not involve significant desensitization of this receptor. Perfusion of a GABA transporter inhibitor (NO-711), glutamate receptor inhibitors CNQX and APV, or a gap junctional blocker (carbenoxolone) prevented the resurgence of large IPSCs. Pressure ejected sucrose resulted in the abolishment of subsequent surges. No elevated K(+)-mediated surges were observed in CA3 interneurons from the stratum oriens layer. In conclusion, these cyclic large IPSC events observable in CA3 pyramidal neurons in 10 mM KCl may be due to transient GABA depletion from continuously active interneuronal afferents.

  15. 78 FR 65161 - Airworthiness Directives; Agusta S.p.A. (Type Certificate Currently Held by AgustaWestland S.p.A...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-31

    ... Federal Aviation Administration 14 CFR Part 39 [Docket No. FAA-2013-0518; Directorate Identifier 2009-SW... Certificate Currently Held by AgustaWestland S.p.A) (Agusta) Helicopters AGENCY: Federal Aviation... INFORMATION CONTACT: Chinh Vuong, Aviation Safety Engineer, Safety Management Group, Rotorcraft Directorate...

  16. 78 FR 40640 - Airworthiness Directives; Agusta S.p.A. (Type Certificate Currently Held by AgustaWestland S.p.A...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-08

    ... helicopters. The existing AD currently requires inspecting the fuselage frame to detect fatigue cracks which... inspecting the fuselage frame for a fatigue crack. This proposed AD would require inspecting the fuselage frame for a crack, but would reduce the applicability from the existing AD to exclude...

  17. High Temperature Stability of Potassium Beta Alumina

    NASA Technical Reports Server (NTRS)

    Williams, R. M.; Kisor, A.; Ryan, M. A.

    1996-01-01

    None. From Objectives section: Evaluate the stability of potassium beta alumina under potassium AMTEC operating conditions. Evaluate the stability regime in which potassium beta alumina can be fabricated.

  18. Recipe for potassium

    SciTech Connect

    Izutani, Natsuko

    2012-11-12

    I investigate favorable conditions for producing potassium (K). Observations show [K/Fe] > 0 at low metallicities, while zero-metal supernova models show low [K/Fe] (< 0). Theoretically, it is natural that the odd-Z element, potassium decreases with lower metallicity, and thus, the observation should imply new and unknown sites for potassium. In this proceedings, I calculate proton-rich nucleosynthesis with three parameters, the initial Y{sub e} (from 0.51 to 0.60), the initial density {rho}{sub max} (10{sup 7}, 10{sup 8}, and 10{sup 9} [g/cm{sup 3}]), and the e-fold time {tau} for the density (0.01, 0.1, and 1.0 [sec]). Among 90 models I have calculated, only 26 models show [K/Fe] > 0, and they all have {rho}{sub max} = 10{sup 9}[g/cm{sup 3}]. I discuss parameter dependence of [K/Fe].

  19. Potassium Beta-Alumina/Molybdenum/Potassium Electrochemical Cells

    NASA Technical Reports Server (NTRS)

    Williams, R.; Kisor, A.; Ryan, M.; Nakamura, B.; Kikert, S.; O'Connor, D.

    1994-01-01

    potassium alkali metal thermal-to-electric converter (K-AMTEC) cells utilizing potassium beta alumina solid electrolyte (K-BASE) are predicted to have improved properties for thermal to electric conversion at somewhat lower temperatures than sodium AMTEC's.

  20. Errors in potassium balance

    SciTech Connect

    Forbes, G.B.; Lantigua, R.; Amatruda, J.M.; Lockwood, D.H.

    1981-01-01

    Six overweight adult subjects given a low calorie diet containing adequate amounts of nitrogen but subnormal amounts of potassium (K) were observed on the Clinical Research Center for periods of 29 to 40 days. Metabolic balance of potassium was measured together with frequent assays of total body K by /sup 40/K counting. Metabolic K balance underestimated body K losses by 11 to 87% (average 43%): the intersubject variability is such as to preclude the use of a single correction value for unmeasured losses in K balance studies.

  1. Characterization of hERG1a and hERG1b potassium channels-a possible role for hERG1b in the I (Kr) current.

    PubMed

    Larsen, Anders Peter; Olesen, Søren-Peter; Grunnet, Morten; Jespersen, Thomas

    2008-09-01

    I (Kr) is the fast component of the delayed rectifier potassium currents responsible for the repolarization of the cardiac muscle. The molecular correlate underlying the I (Kr) current has been identified as the hERG1 channel. Recently, two splice variants of the hERG1 alpha-subunit, hERG1a and hERG1b, have been shown to be co-expressed in human cardiomyocytes. In this paper, we present the electrophysiological characterization of hERG1a, hERG1b, and co-expressed hERG1a/b channels in a mammalian expression system using the whole-cell patch clamp technique. We also quantified the messenger RNA (mRNA) levels of hERG1a and hERG1b in human cardiac tissue, and based on the expressed ratios, we evaluated the resulting currents in Xenopus laevis oocytes. Compared to hERG1a channels, activation was faster for both hERG1b and hERG1a/b channels. The deactivation kinetics was greatly accelerated in the presence of hERG1b, whereas no difference in the time constant of inactivation was observed. The voltage-dependent recovery from inactivation was also similar. However, the time constant of recovery from inactivation was significantly faster for hERG1b channels compared to hERG1a and hERG1a/b. Quantification of hERG1a and hERG1b mRNA in the human heart showed that hERG1b mRNA constitutes, on average, 19% in the right atrium and 12% in the left ventricle of the total hERG1 mRNA. Expression of the observed ratios of hERG1a to hERG1b in X. laevis oocytes showed that these ratios are indeed sufficient to change the deactivation phenotype markedly. The present work suggests that hERG1b is likely to play a role in the formation of the native I (Kr) current.

  2. What do we not know about mitochondrial potassium channels?

    PubMed

    Laskowski, Michał; Augustynek, Bartłomiej; Kulawiak, Bogusz; Koprowski, Piotr; Bednarczyk, Piotr; Jarmuszkiewicz, Wieslawa; Szewczyk, Adam

    2016-08-01

    In this review, we summarize our knowledge about mitochondrial potassium channels, with a special focus on unanswered questions in this field. The following potassium channels have been well described in the inner mitochondrial membrane: ATP-regulated potassium channel, Ca(2+)-activated potassium channel, the voltage-gated Kv1.3 potassium channel, and the two-pore domain TASK-3 potassium channel. The primary functional roles of these channels include regulation of mitochondrial respiration and the alteration of membrane potential. Additionally, they modulate the mitochondrial matrix volume and the synthesis of reactive oxygen species by mitochondria. Mitochondrial potassium channels are believed to contribute to cytoprotection and cell death. In this paper, we discuss fundamental issues concerning mitochondrial potassium channels: their molecular identity, channel pharmacology and functional properties. Attention will be given to the current problems present in our understanding of the nature of mitochondrial potassium channels. This article is part of a Special Issue entitled 'EBEC 2016: 19th European Bioenergetics Conference, Riva del Garda, Italy, July 2-6, 2016', edited by Prof. Paolo Bernardi. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Potassium urine test

    MedlinePlus

    ... test. Alternative Names Urine potassium Images Male urinary system References Batlle D, Chen S, Haque SK. Physiologic principles in the clinical evaluation of electrolyte, water, and acid-base disorders. In: Alpern RJ, Orson WM, Caplan M, eds. Seldin and Giebisch's The Kidney . ...

  4. Potassium silver cyanide

    Integrated Risk Information System (IRIS)

    Jump to main content . Integrated Risk Information System Recent Additions | Contact Us Search : All EPA IRIS • You are here : EPA Home • Research • Environmental Assessment • IRIS • IRIS Summaries Redirect Page As of September 28 , 2010 , the assessment summary for potassium silver cyanide is inclu

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

    PubMed

    Stern, Shani; Segal, Menahem; Moses, Elisha

    2015-09-01

    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 [Ca(2+)]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.

  6. 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

  7. [What we don't know about mitochondrial potassium channels?

    PubMed

    Augustynek, Bartłomiej; Wrzosek, Antoni; Koprowski, Piotr; Kiełbasa, Agnieszka; Bednarczyk, Piotr; Łukasiak, Agnieszka; Dołowy, Krzysztof; Szewczyk, Adam

    2016-01-01

    In the current work the authors present the most interesting, yet not fully understood issues regarding origin, function and pharmacology of the mitochondrial potassium channels. There are eight potassium channels known to contribute to the potassium permeability of the inner mitochondrial membrane: ATP-regulated channel, calcium-regulated channels of large, intermediate and small conductance, voltage-regulated Kv1.3 and Kv7.4 channels, two-pore-domain TASK-3 channel and SLO2 channel. The primary function of the mitochondrial potassium channels is regulation of the mitochondrial membrane potential. Additionally, mitochondrial potassium channels alter cellular respiration, regulation of the mitochondrial volume and ROS synthesis. However, mechanisms underlying these processes are not fully understood yet. In this work, the authors not only present available knowledge about this topic, but also put certain hypotheses that may set the direction for the future research on these proteins.

  8. Detecting potassium on Mercury

    NASA Technical Reports Server (NTRS)

    Killen, R. M.; Potter, A. E.; Morgan, T. H.

    1991-01-01

    A critical comment on the work of A.L. Sprague et al. (1990) is presented. It is argued that, in attributing an enhanced emission in the potassium D lines on Oct. 14, 1987 in the equatorial region of Mercury to a diffusion source centered on Caloris Basin, Sprague et al. misinterpreted the data. Sprague et al. present a reply, taking issue with the commenters.

  9. [Diet low in potassium].

    PubMed

    Sáez Rodríguez, Loreto; Meizoso Ameneiro, Ana; Pérez Paz, Ma Jesús; Valiño Pazos, Cristina

    2011-11-01

    After confirming the high prevalence rates in our hemodialysis unit of the following nursing diagnoses: nutritional imbalances--both excesses and shortages, willingness to improve nutrition and fear related to the consequences of excessive intake of potassium and manifested by the inhibition in some people towards the enjoyment of food, we decided to plan an educational strategy which later resulted in a nursing intervention for these diagnoses, with the objective of providing adequate resources for the monitoring of balanced diets with a restriction of potassium. Inspired by dietary rations, as well as recognized dietary programs of learning by points, we decided to incorporate these ideas to design an educational tool to facilitate advice to our patients on how to follow diet plans as well as the choice of appropriate foods. The result was a set of cards incorporating nutritional information of various kinds, aimed at our patients covering different aspects of the diet appropriate food rations using household measurements, promoting good food preparation, appropriate dietary advice for different chronic diseases and a scoring system of foods according to their potassium content. Together they form a board game available during the hemodialysis sessions that also takes into consideration other issues of importance related to conditions such as cognitive stimulation, coping with the disease, improving the therapeutic performance or resources to increase patient motivation. Although initially it was only an educational exercise, the result has turned out to be both enjoyable and entertaining.

  10. Potassium Channelopathies and Gastrointestinal Ulceration

    PubMed Central

    Han, Jaeyong; Lee, Seung Hun; Giebisch, Gerhard; Wang, Tong

    2016-01-01

    Potassium channels and transporters maintain potassium homeostasis and play significant roles in several different biological actions via potassium ion regulation. In previous decades, the key revelations that potassium channels and transporters are involved in the production of gastric acid and the regulation of secretion in the stomach have been recognized. Drugs used to treat peptic ulceration are often potassium transporter inhibitors. It has also been reported that potassium channels are involved in ulcerative colitis. Direct toxicity to the intestines from nonsteroidal anti-inflammatory drugs has been associated with altered potassium channel activities. Several reports have indicated that the long-term use of the antianginal drug Nicorandil, an adenosine triphosphate-sensitive potassium channel opener, increases the chances of ulceration and perforation from the oral to anal regions throughout the gastrointestinal (GI) tract. Several of these drug features provide further insights into the role of potassium channels in the occurrence of ulceration in the GI tract. The purpose of this review is to investigate whether potassium channelopathies are involved in the mechanisms responsible for ulceration that occurs throughout the GI tract. PMID:27784845

  11. Simultaneous determination of potassium and rubidium content in yeast.

    PubMed

    Mulet, Jose M; Serrano, Ramón

    2002-11-01

    Rubidium is widely used as a potassium analogue in transport studies in yeast and other organisms. As rubidium (potassium) uptake is modulated by the internal potassium concentration, it is often necessary to determine both Rb(+) and K(+) concentrations in the same cell extract. Current methods based on atomic absorption/emission spectroscopy require separate analysis for each cation. Alternatively, unsafe radioactive isotopes can be used. Here we report a convenient, non-radioactive, HPLC/conductivity-based method that allows a complete analysis of both cations with a single injection from a cell extract. The increase in Rb(+) uptake during K(+) starvation in yeast is easily demonstrated with this method.

  12. Longitudinal magnetoresistance of potassium

    NASA Astrophysics Data System (ADS)

    Huberman, M. L.

    1987-06-01

    Recently, Zhu and Overhauser showed that the Hall coefficient of potassium is anisotropic, depending on the angle between the applied magnetic field and the charge-density wave. It follows that the Hall coefficient of a polydomain sample is inhomogeneous. By means of effective-medium theory, the magnetoresistance of a domain structure has been evaluated. It is shown that both the longitudinal and transverse magnetoresistance increase with increasing field. The Kohler slope depends on the domain distribution. For a random distribution, the longitudinal and transverse Kohler slopes are about (1/2)% and 1(1/2)%, respectively.

  13. Thermal magnetoresistance of potassium

    NASA Astrophysics Data System (ADS)

    Huberman, M. L.

    1988-11-01

    It has recently been shown that an inhomogeneous, anisotropic Hall coefficient, arising from a charge-density-wave domain structure, explains the nonsaturating electrical magnetoresistance of potassium. It is shown here that the same mechanism also explains the observed behavior of the thermal magnetoresistance. The transverse thermal magnetoresistance of a domain structure increases with increasing field, having both a linear and quadratic component. The longitudinal thermal magnetoresistance of a domain structure initially increases linearly with increasing field. Its behavior in higher fields, however, depends on whether or not the domain distribution is symmetric about the field direction. If the distribution is symmetric, saturation occurs; otherwise, a residual increase is possible.

  14. 21 CFR 184.1643 - Potassium sulfate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Potassium sulfate. 184.1643 Section 184.1643 Food... GRAS § 184.1643 Potassium sulfate. (a) Potassium sulfate (K2SO4, CAS Reg. No. 7778-80-5) occurs.... It is prepared by the neutralization of sulfuric acid with potassium hydroxide or potassium carbonate...

  15. 21 CFR 184.1631 - Potassium hydroxide.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Potassium hydroxide. 184.1631 Section 184.1631... GRAS § 184.1631 Potassium hydroxide. (a) Potassium hydroxide (KOH, CAS Reg. No. 1310-58-3) is also... powders. Potassium hydroxide is obtained commercially from the electrolysis of potassium chloride solution...

  16. 21 CFR 184.1619 - Potassium carbonate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Potassium carbonate. 184.1619 Section 184.1619 Food... Specific Substances Affirmed as GRAS § 184.1619 Potassium carbonate. (a) Potassium carbonate (K2CO3, CAS... potassium chloride followed by exposing the resultant potassium to carbon dioxide; (2) By treating a...

  17. 21 CFR 172.800 - Acesulfame potassium.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Acesulfame potassium. 172.800 Section 172.800 Food... Multipurpose Additives § 172.800 Acesulfame potassium. Acesulfame potassium (CAS Reg. No. 55589-62-3), also... not preclude such use, under the following conditions: (a) Acesulfame potassium is the potassium salt...

  18. 21 CFR 184.1619 - Potassium carbonate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Potassium carbonate. 184.1619 Section 184.1619... Listing of Specific Substances Affirmed as GRAS § 184.1619 Potassium carbonate. (a) Potassium carbonate... of potassium chloride followed by exposing the resultant potassium to carbon dioxide; (2) By treating...

  19. 21 CFR 184.1613 - Potassium bicarbonate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Potassium bicarbonate. 184.1613 Section 184.1613... Listing of Specific Substances Affirmed as GRAS § 184.1613 Potassium bicarbonate. (a) Potassium... potassium hydroxide with carbon dioxide; (2) By treating a solution of potassium carbonate with carbon...

  20. 21 CFR 172.800 - Acesulfame potassium.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Acesulfame potassium. 172.800 Section 172.800 Food... Multipurpose Additives § 172.800 Acesulfame potassium. Acesulfame potassium (CAS Reg. No. 55589-62-3), also... not preclude such use, under the following conditions: (a) Acesulfame potassium is the potassium salt...

  1. 21 CFR 184.1619 - Potassium carbonate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Potassium carbonate. 184.1619 Section 184.1619... Listing of Specific Substances Affirmed as GRAS § 184.1619 Potassium carbonate. (a) Potassium carbonate... of potassium chloride followed by exposing the resultant potassium to carbon dioxide; (2) By treating...

  2. 21 CFR 172.800 - Acesulfame potassium.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Acesulfame potassium. 172.800 Section 172.800 Food... Multipurpose Additives § 172.800 Acesulfame potassium. Acesulfame potassium (CAS Reg. No. 55589-62-3), also... not preclude such use, under the following conditions: (a) Acesulfame potassium is the potassium salt...

  3. 21 CFR 184.1613 - Potassium bicarbonate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Potassium bicarbonate. 184.1613 Section 184.1613... Listing of Specific Substances Affirmed as GRAS § 184.1613 Potassium bicarbonate. (a) Potassium... potassium hydroxide with carbon dioxide; (2) By treating a solution of potassium carbonate with carbon...

  4. 21 CFR 184.1619 - Potassium carbonate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Potassium carbonate. 184.1619 Section 184.1619... Listing of Specific Substances Affirmed as GRAS § 184.1619 Potassium carbonate. (a) Potassium carbonate... of potassium chloride followed by exposing the resultant potassium to carbon dioxide; (2) By treating...

  5. 21 CFR 184.1613 - Potassium bicarbonate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Potassium bicarbonate. 184.1613 Section 184.1613... Listing of Specific Substances Affirmed as GRAS § 184.1613 Potassium bicarbonate. (a) Potassium... potassium hydroxide with carbon dioxide; (2) By treating a solution of potassium carbonate with carbon...

  6. 21 CFR 172.800 - Acesulfame potassium.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Acesulfame potassium. 172.800 Section 172.800 Food... Multipurpose Additives § 172.800 Acesulfame potassium. Acesulfame potassium (CAS Reg. No. 55589-62-3), also... not preclude such use, under the following conditions: (a) Acesulfame potassium is the potassium salt...

  7. 21 CFR 184.1613 - Potassium bicarbonate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Potassium bicarbonate. 184.1613 Section 184.1613... Listing of Specific Substances Affirmed as GRAS § 184.1613 Potassium bicarbonate. (a) Potassium... potassium hydroxide with carbon dioxide; (2) By treating a solution of potassium carbonate with carbon...

  8. Total body potassium measurement method

    SciTech Connect

    Tomlinson, F.K.

    1985-09-01

    The body counter facility at Mound was used to measure the total body potassium (TBK) in hypertensive patients. Radioactive /sup 40/K accounts for 0.0118% of natural potassium and can be readily measured in vivo. The normal adult human generally has 80 to 185 g of TBK depending on sex, age, height, etc. 10 refs., 1 tab.

  9. Sodium and potassium in the lunar atmosphere

    NASA Technical Reports Server (NTRS)

    Potter, A. E.; Morgan, T. H.

    1991-01-01

    The discovery that sodium and potassium vapor can be observed in the lunar atmosphere using ground-based telescopes has opened up a field of investigation that was closed after the last Apollo mission to the Moon. Sodium has been detected at altitudes up to 1500 km above the surface. This implies a high effective temperature for sodium, of the order of 1000 K. However, there is some evidence for two populations of sodium and potassium, one at temperatures corresponding to the surface, and another corresponding to high temperatures. The sources for the lunar atmosphere are not understood. Meteoric bombardment of the surface, solar wind sputtering of the surface, and photo-sputtering of the surface have all been suggested as possible sources for the lunar atmosphere. One of the objectives of the current research is to test different hypotheses by measurements of the atmosphere under different conditions of solar illumination and shielding from the solar wind by the Earth.

  10. Oral potassium supplementation in surgical patients.

    PubMed

    Hainsworth, Alison J; Gatenby, Piers A

    2008-08-01

    Hospital inpatients are frequently hypokalaemic. Low plasma potassium levels may cause life threatening complications, such as cardiac arrhythmias. Potassium supplementation may be administered parenterally or enterally. Oral potassium supplements have been associated with oesophageal ulceration, strictures and gastritis. An alternative to potassium salt tablets or solution is dietary modification with potassium rich food stuffs, which has been proven to be a safe and effective method for potassium supplementation. The potassium content of one medium banana is equivalent to a 12 mmol potassium salt tablet. Potassium supplementation by dietary modification has been shown to be equally efficacious to oral potassium salt supplementation and is preferred by the majority of patients. Subsequently, it is our practice to replace potassium using dietary modification, particularly in surgical patients having undergone oesophagogastrectomy or in those with peptic ulcer disease.

  11. Historical and technical developments of potassium resources.

    PubMed

    Ciceri, Davide; Manning, David A C; Allanore, Antoine

    2015-01-01

    The mining of soluble potassium salts (potash) is essential for manufacturing fertilizers required to ensure continuous production of crops and hence global food security. As of 2014, potash is mined predominantly in the northern hemisphere, where large deposits occur. Production tonnage and prices do not take into account the needs of the farmers of the poorest countries. Consequently, soils of some regions of the southern hemisphere are currently being depleted of potassium due to the expansion and intensification of agriculture coupled with the lack of affordable potash. Moving away from mined salts towards locally available resources of potassium, such as K-bearing silicates, could be one option to improve this situation. Overall, the global potash production system and its sustainability warrant discussion. In this contribution we examine the history of potash production and discuss the different sources and technologies used throughout the centuries. In particular, we highlight the political and economic conditions that favored the development of one specific technology over another. We identified a pattern of needs driving innovation. We show that as needs evolved throughout history, alternatives to soluble salts have been used to obtain K-fertilizers. Those alternatives may meet the incoming needs of our century, providing the regulatory and advisory practices that prevailed in the 20th century are revised. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. 21 CFR 184.1635 - Potassium iodate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Potassium iodate. 184.1635 Section 184.1635 Food... Specific Substances Affirmed as GRAS § 184.1635 Potassium iodate. (a) Potassium iodate (KIO3, CAS Reg. No. 7758-05-6) does not occur naturally but can be prepared by reacting iodine with potassium hydroxide. (b...

  13. 21 CFR 184.1631 - Potassium hydroxide.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Potassium hydroxide. 184.1631 Section 184.1631... Listing of Specific Substances Affirmed as GRAS § 184.1631 Potassium hydroxide. (a) Potassium hydroxide..., including pellets, flakes, sticks, lumps, and powders. Potassium hydroxide is obtained commercially from the...

  14. 21 CFR 172.375 - Potassium iodide.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Potassium iodide. 172.375 Section 172.375 Food and... Dietary and Nutritional Additives § 172.375 Potassium iodide. The food additive potassium iodide may be safely used in accordance with the following prescribed conditions: (a) Potassium iodide may be safely...

  15. 21 CFR 184.1610 - Potassium alginate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Potassium alginate. 184.1610 Section 184.1610 Food... Specific Substances Affirmed as GRAS § 184.1610 Potassium alginate. (a) Potassium alginate (CAS Reg. No. 9005-36-1) is the potassium salt of alginic acid, a natural polyuronide constituent of certain brown...

  16. 21 CFR 172.375 - Potassium iodide.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Potassium iodide. 172.375 Section 172.375 Food and... Dietary and Nutritional Additives § 172.375 Potassium iodide. The food additive potassium iodide may be safely used in accordance with the following prescribed conditions: (a) Potassium iodide may be safely...

  17. 21 CFR 184.1631 - Potassium hydroxide.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Potassium hydroxide. 184.1631 Section 184.1631... Listing of Specific Substances Affirmed as GRAS § 184.1631 Potassium hydroxide. (a) Potassium hydroxide..., including pellets, flakes, sticks, lumps, and powders. Potassium hydroxide is obtained commercially from the...

  18. 21 CFR 184.1622 - Potassium chloride.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Potassium chloride. 184.1622 Section 184.1622 Food... GRAS § 184.1622 Potassium chloride. (a) Potassium chloride (KCl, CAS Reg. No. 7447-40-7) is a white... manufacturing practice. Potassium chloride may be used in infant formula in accordance with section 412(g) of...

  19. 21 CFR 184.1631 - Potassium hydroxide.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Potassium hydroxide. 184.1631 Section 184.1631 Food... Specific Substances Affirmed as GRAS § 184.1631 Potassium hydroxide. (a) Potassium hydroxide (KOH, CAS Reg... pellets, flakes, sticks, lumps, and powders. Potassium hydroxide is obtained commercially from the...

  20. 21 CFR 184.1634 - Potassium iodide.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Potassium iodide. 184.1634 Section 184.1634 Food... Specific Substances Affirmed as GRAS § 184.1634 Potassium iodide. (a) Potassium iodide (KI, CAS Reg. No. 7681-11-0) is the potassium salt of hydriodic acid. It occurs naturally in sea water and in salt...

  1. 21 CFR 184.1643 - Potassium sulfate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Potassium sulfate. 184.1643 Section 184.1643 Food... Specific Substances Affirmed as GRAS § 184.1643 Potassium sulfate. (a) Potassium sulfate (K2SO4, CAS Reg... having a bitter, saline taste. It is prepared by the neutralization of sulfuric acid with potassium...

  2. 21 CFR 184.1610 - Potassium alginate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Potassium alginate. 184.1610 Section 184.1610 Food... Specific Substances Affirmed as GRAS § 184.1610 Potassium alginate. (a) Potassium alginate (CAS Reg. No. 9005-36-1) is the potassium salt of alginic acid, a natural polyuronide constituent of certain brown...

  3. 21 CFR 184.1619 - Potassium carbonate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Potassium carbonate. 184.1619 Section 184.1619... GRAS § 184.1619 Potassium carbonate. (a) Potassium carbonate (K2CO3, CAS Reg. No. 584-08-7) is produced by the following methods of manufacture: (1) By electrolysis of potassium chloride followed by...

  4. 21 CFR 184.1635 - Potassium iodate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Potassium iodate. 184.1635 Section 184.1635 Food... Specific Substances Affirmed as GRAS § 184.1635 Potassium iodate. (a) Potassium iodate (KIO3, CAS Reg. No. 7758-05-6) does not occur naturally but can be prepared by reacting iodine with potassium hydroxide. (b...

  5. 21 CFR 172.375 - Potassium iodide.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Potassium iodide. 172.375 Section 172.375 Food and... Dietary and Nutritional Additives § 172.375 Potassium iodide. The food additive potassium iodide may be safely used in accordance with the following prescribed conditions: (a) Potassium iodide may be safely...

  6. 21 CFR 184.1634 - Potassium iodide.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Potassium iodide. 184.1634 Section 184.1634 Food... Specific Substances Affirmed as GRAS § 184.1634 Potassium iodide. (a) Potassium iodide (KI, CAS Reg. No. 7681-11-0) is the potassium salt of hydriodic acid. It occurs naturally in sea water and in salt...

  7. 21 CFR 184.1631 - Potassium hydroxide.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Potassium hydroxide. 184.1631 Section 184.1631... Listing of Specific Substances Affirmed as GRAS § 184.1631 Potassium hydroxide. (a) Potassium hydroxide..., including pellets, flakes, sticks, lumps, and powders. Potassium hydroxide is obtained commercially from the...

  8. 21 CFR 184.1610 - Potassium alginate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Potassium alginate. 184.1610 Section 184.1610 Food... Specific Substances Affirmed as GRAS § 184.1610 Potassium alginate. (a) Potassium alginate (CAS Reg. No. 9005-36-1) is the potassium salt of alginic acid, a natural polyuronide constituent of certain brown...

  9. 21 CFR 172.375 - Potassium iodide.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Potassium iodide. 172.375 Section 172.375 Food and....375 Potassium iodide. The food additive potassium iodide may be safely used in accordance with the following prescribed conditions: (a) Potassium iodide may be safely added to a food as a source of the...

  10. 21 CFR 184.1610 - Potassium alginate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Potassium alginate. 184.1610 Section 184.1610 Food... Specific Substances Affirmed as GRAS § 184.1610 Potassium alginate. (a) Potassium alginate (CAS Reg. No. 9005-36-1) is the potassium salt of alginic acid, a natural polyuronide constituent of certain brown...

  11. 21 CFR 184.1634 - Potassium iodide.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Potassium iodide. 184.1634 Section 184.1634 Food... Specific Substances Affirmed as GRAS § 184.1634 Potassium iodide. (a) Potassium iodide (KI, CAS Reg. No. 7681-11-0) is the potassium salt of hydriodic acid. It occurs naturally in sea water and in salt...

  12. 21 CFR 184.1643 - Potassium sulfate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Potassium sulfate. 184.1643 Section 184.1643 Food... Specific Substances Affirmed as GRAS § 184.1643 Potassium sulfate. (a) Potassium sulfate (K2SO4, CAS Reg... having a bitter, saline taste. It is prepared by the neutralization of sulfuric acid with potassium...

  13. 21 CFR 184.1635 - Potassium iodate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Potassium iodate. 184.1635 Section 184.1635 Food... Specific Substances Affirmed as GRAS § 184.1635 Potassium iodate. (a) Potassium iodate (KIO3, CAS Reg. No. 7758-05-6) does not occur naturally but can be prepared by reacting iodine with potassium hydroxide. (b...

  14. 21 CFR 184.1643 - Potassium sulfate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Potassium sulfate. 184.1643 Section 184.1643 Food... Specific Substances Affirmed as GRAS § 184.1643 Potassium sulfate. (a) Potassium sulfate (K2SO4, CAS Reg... having a bitter, saline taste. It is prepared by the neutralization of sulfuric acid with potassium...

  15. 21 CFR 184.1643 - Potassium sulfate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Potassium sulfate. 184.1643 Section 184.1643 Food... Specific Substances Affirmed as GRAS § 184.1643 Potassium sulfate. (a) Potassium sulfate (K2SO4, CAS Reg... having a bitter, saline taste. It is prepared by the neutralization of sulfuric acid with potassium...

  16. 21 CFR 184.1635 - Potassium iodate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Potassium iodate. 184.1635 Section 184.1635 Food... Specific Substances Affirmed as GRAS § 184.1635 Potassium iodate. (a) Potassium iodate (KIO3, CAS Reg. No. 7758-05-6) does not occur naturally but can be prepared by reacting iodine with potassium hydroxide. (b...

  17. 21 CFR 184.1634 - Potassium iodide.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Potassium iodide. 184.1634 Section 184.1634 Food... Specific Substances Affirmed as GRAS § 184.1634 Potassium iodide. (a) Potassium iodide (KI, CAS Reg. No. 7681-11-0) is the potassium salt of hydriodic acid. It occurs naturally in sea water and in salt...

  18. Potassium Disorders: Hypokalemia and Hyperkalemia.

    PubMed

    Viera, Anthony J; Wouk, Noah

    2015-09-15

    Hypokalemia and hyperkalemia are common electrolyte disorders caused by changes in potassium intake, altered excretion, or transcellular shifts. Diuretic use and gastrointestinal losses are common causes of hypokalemia, whereas kidney disease, hyperglycemia, and medication use are common causes of hyperkalemia. When severe, potassium disorders can lead to life-threatening cardiac conduction disturbances and neuromuscular dysfunction. Therefore, a first priority is determining the need for urgent treatment through a combination of history, physical examination, laboratory, and electrocardiography findings. Indications for urgent treatment include severe or symptomatic hypokalemia or hyperkalemia; abrupt changes in potassium levels; electrocardiography changes; or the presence of certain comorbid conditions. Hypokalemia is treated with oral or intravenous potassium. To prevent cardiac conduction disturbances, intravenous calcium is administered to patients with hyperkalemic electrocardiography changes. Insulin, usually with concomitant glucose, and albuterol are preferred to lower serum potassium levels in the acute setting; sodium polystyrene sulfonate is reserved for subacute treatment. For both disorders, it is important to consider potential causes of transcellular shifts because patients are at increased risk of rebound potassium disturbances.

  19. [Potassium channelopathies and Morvan's syndromes].

    PubMed

    Serratrice, Georges; Pellissier, Jean-François; Serra-Trice, Jacques; Weiller, Pierre-Jean

    2010-02-01

    Interest in Morvan's disease or syndrome has grown, owing to its close links with various potassium channelopathies. Potassium is crucial for gating mechanisms (channel opening and closing), and especially for repolarization. Defective potassium regulation can lead to neuronal hyperexcitability. There are three families of potassium channels: voltage-gated potassium channels or VGKC (Kv1.1-Kv1.8), inward rectifier K+ channels (Kir), and two-pore channels (K2p). VGK channels are the commonest, and especially those belonging to the Shaker group (neuromyotonia and Morvan's syndrome, limbic encephalitis, and type 1 episodic ataxia). Brain and heart K+ channelopathies are a separate group due to KCNQ1 mutation (severe type 2 long QT syndrome). Kv7 channel mutations (in KNQ2 and KCNQ3) are responsible for benign familial neonatal seizures. Mutation of the Ca+ activated K+ channel gene causes epilepsy and paroxysmal dyskinesia. Inward rectifier K+ channels regulate intracellular potassium levels. The DEND syndrome, a treatable channelopathy of the brain and pancreas, is due to KCNJ1 mutation. Andersen's syndrome, due to KCNJ2 mutation, is characterized by periodic paralysis, cardiac arrythmia, and dysmorphia. Voltage-insensitive K2p channelopathies form a final group.

  20. 21 CFR 184.1625 - Potassium citrate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Potassium citrate. 184.1625 Section 184.1625 Food... GRAS § 184.1625 Potassium citrate. (a) Potassium citrate (C6H5K3O7·H2O, CAS Reg. No. 006100-0905-096) is the potassium salt of citric acid. It is prepared by neutralizing citric acid with potassium...

  1. DPPX potassium channel antibody

    PubMed Central

    Tobin, William Oliver; Lennon, Vanda A.; Komorowski, Lars; Probst, Christian; Clardy, Stacey Lynn; Aksamit, Allen J.; Appendino, Juan Pablo; Lucchinetti, Claudia F.; Matsumoto, Joseph Y.; Pittock, Sean J.; Sandroni, Paola; Tippmann-Peikert, Maja; Wirrell, Elaine C.

    2014-01-01

    Objective: To describe the detection frequency and clinical associations of immunoglobulin G (IgG) targeting dipeptidyl-peptidase-like protein-6 (DPPX), a regulatory subunit of neuronal Kv4.2 potassium channels. Methods: Specimens from 20 patients evaluated on a service basis by tissue-based immunofluorescence yielded a synaptic immunostaining pattern consistent with DPPX-IgG (serum, 20; CSF, all 7 available). Transfected HEK293 cell-based assay confirmed DPPX specificity in all specimens. Sixty-nine patients with stiff-person syndrome and related disorders were also evaluated by DPPX-IgG cell-based assay. Results: Of 20 seropositive patients, 12 were men; median symptom onset age was 53 years (range, 13–75). Symptom onset was insidious in 15 and subacute in 5. Twelve patients reported prodromal weight loss. Neurologic disorders were multifocal. All had one or more brain or brainstem manifestations: amnesia (16), delirium (8), psychosis (4), depression (4), seizures (2), and brainstem disorders (15; eye movement disturbances [8], ataxia [7], dysphagia [6], dysarthria [4], respiratory failure [3]). Nine patients reported sleep disturbance. Manifestations of central hyperexcitability included myoclonus (8), exaggerated startle (6), diffuse rigidity (6), and hyperreflexia (6). Dysautonomia involved the gastrointestinal tract (9; diarrhea [6], gastroparesis, and constipation [3]), bladder (7), cardiac conduction system (3), and thermoregulation (1). Two patients had B-cell neoplasms: gastrointestinal lymphoma (1), and chronic lymphocytic leukemia (1). Substantial neurologic improvements followed immunotherapy in 7 of 11 patients with available treatment data. DPPX-IgG was not detected in any of the stiff-person syndrome patients. Conclusions: DPPX-IgG is a biomarker for an immunotherapy-responsive multifocal neurologic disorder of the central and autonomic nervous systems. PMID:25320100

  2. Active dendrites, potassium channels and synaptic plasticity.

    PubMed Central

    Johnston, Daniel; Christie, Brian R; Frick, Andreas; Gray, Richard; Hoffman, Dax A; Schexnayder, Lalania K; Watanabe, Shigeo; Yuan, Li-Lian

    2003-01-01

    The dendrites of CA1 pyramidal neurons in the hippocampus express numerous types of voltage-gated ion channel, but the distributions or densities of many of these channels are very non-uniform. Sodium channels in the dendrites are responsible for action potential (AP) propagation from the axon into the dendrites (back-propagation); calcium channels are responsible for local changes in dendritic calcium concentrations following back-propagating APs and synaptic potentials; and potassium channels help regulate overall dendritic excitability. Several lines of evidence are presented here to suggest that back-propagating APs, when coincident with excitatory synaptic input, can lead to the induction of either long-term depression (LTD) or long-term potentiation (LTP). The induction of LTD or LTP is correlated with the magnitude of the rise in intracellular calcium. When brief bursts of synaptic potentials are paired with postsynaptic APs in a theta-burst pairing paradigm, the induction of LTP is dependent on the invasion of the AP into the dendritic tree. The amplitude of the AP in the dendrites is dependent, in part, on the activity of a transient, A-type potassium channel that is expressed at high density in the dendrites and correlates with the induction of the LTP. Furthermore, during the expression phase of the LTP, there are local changes in dendritic excitability that may result from modulation of the functioning of this transient potassium channel. The results support the view that the active properties of dendrites play important roles in synaptic integration and synaptic plasticity of these neurons. PMID:12740112

  3. Ion-Switchable Quantum Dot Förster Resonance Energy Transfer Rates in Ratiometric Potassium Sensors.

    PubMed

    Ruckh, Timothy T; Skipwith, Christopher G; Chang, Wendi; Senko, Alexander W; Bulovic, Vladimir; Anikeeva, Polina O; Clark, Heather A

    2016-04-26

    The tools for optically imaging cellular potassium concentrations in real-time are currently limited to a small set of molecular indicator dyes. Quantum dot-based nanosensors are more photostable and tunable than organic indicators, but previous designs have fallen short in size, sensitivity, and selectivity. Here, we introduce a small, sensitive, and selective nanosensor for potassium measurements. A dynamic quencher modulates the fluorescence emitted by two different quantum dot species to produce a ratiometric signal. We characterized the potassium-modulated sensor properties and investigated the photonic interactions within the sensors. The quencher's protonation changes in response to potassium, which modulates its Förster radiative energy transfer rate and the corresponding interaction radii with each quantum dot species. The nanosensors respond to changes in potassium concentrations typical of the cellular environment and thus provide a promising tool for imaging potassium fluxes during biological events.

  4. Cold blood--potassium cardioplegia.

    PubMed

    Levinsky, L; Lee, A B; Lee, K C; Tatransky, F; Dockstader, R; Schimert, G

    1980-09-01

    A technique is described for providing myocardial protection utilizing oxygenated blood that is drawn from the pump oxygenator and passed through two disposable cardioplegic cooling coils, which are joined in series and submerged in ice slush. A potassium-containing cardioplegic solution is run into the oxygenated blood at the level of the cooling coils. The amount of blood used in the blood-potassium cardioplegic mixture is controlled using a screw clamp. This method has been used with excellent results in 150 consecutive patients undergoing aortocoronary saphenous vein bypass grafting.

  5. Contribution of dairy products to dietary potassium intake in the United States population.

    PubMed

    McGill, Carla R; Fulgoni, Victor L; DiRienzo, Douglas; Huth, Peter J; Kurilich, Anne C; Miller, Gregory D

    2008-02-01

    Adequate dietary potassium intake is associated with a reduced risk of cardiovascular and other chronic diseases. The Dietary Guidelines for Americans 2005 identifies milk and milk products as a major contributor of dietary potassium and lists dairy products, along with fruits and vegetables, as food groups to encourage. This paper further examines the impact of dairy consumption on the potassium intake of the United States (US) population. Using data from the National Health and Nutrition Examination Survey (NHANES) 1999-2002 we determined potassium intakes for various age groups of individuals who met the recommended number of dairy servings compared to those who did not. We also examined the impact of dairy servings consumed on mean and median potassium intakes and compared intakes to the age-appropriate Adequate Intakes (AI). For all age groups, mean and median potassium intakes did not meet the respective AI. Mean potassium intakes were significantly greater in those subjects who met dairy intake recommendations compared to those who did not for all age groups. Mean and median potassium intakes increased with increasing dairy intake but were below current intake recommendations for all age groups analyzed. For adults age 19 to 50, 16.1% consumed the recommended number of dairy servings per day. For those 51 and older, 10.7% met current dairy intake recommendations. Consumption of dairy products is below current recommendations which contributes in part to suboptimal dietary potassium intakes among a large proportion of the US population. Since adequate potassium intake is associated with decreased risk of chronic disease, consumption of a variety of potassium-rich foods, including fruits, vegetables and low-fat and fat free dairy products, should continue to be encouraged.

  6. Physiology and pathophysiology of potassium homeostasis.

    PubMed

    Palmer, Biff F; Clegg, Deborah J

    2016-12-01

    Total body potassium content and proper distribution of potassium across the cell membrane is of critical importance for normal cellular function. Potassium homeostasis is maintained by several different methods. In the kidney, total body potassium content is achieved by alterations in renal excretion of potassium in response to variations in intake. Insulin and beta-adrenergic tone play critical roles in maintaining the internal distribution of potassium under normal conditions. Despite homeostatic pathways designed to maintain potassium levels within the normal range, disorders of altered potassium homeostasis are common. The clinical approach to designing effective treatments relies on understanding the pathophysiology and regulatory influences which govern the internal distribution and external balance of potassium. Here we provide an overview of the key regulatory aspects of normal potassium physiology. This review is designed to provide an overview of potassium homeostasis as well as provide references of seminal papers to guide the reader into a more in depth discussion of the importance of potassium balance. This review is designed to be a resource for educators and well-informed clinicians who are teaching trainees about the importance of potassium balance. Copyright © 2016 the American Physiological Society.

  7. Extrarenal potassium adaptation: role of skeletal muscle

    SciTech Connect

    Blachley, J.D.; Crider, B.P.; Johnson, J.H.

    1986-08-01

    Following the ingestion of a high-potassium-content diet for only a few days, the plasma potassium of rats rises only modestly in response to a previously lethal dose of potassium salts. This acquired tolerance, termed potassium adaptation, is principally the result of increased capacity to excrete potassium into the urine. However, a substantial portion of the acute potassium dose is not immediately excreted and is apparently translocated into cells. Previous studies have failed to show an increase in the content of potassium of a variety of tissues from such animals. Using /sup 86/Rb as a potassium analogue, we have shown that the skeletal muscle of potassium-adapted rats takes up significantly greater amounts of potassium in vivo in response to an acute challenge than does that of control animals. Furthermore, the same animals exhibit greater efflux of /sup 86/Rb following the termination of the acute infusion. We have also shown that the Na+-K+-ATPase activity and ouabain-binding capacity of skeletal muscle microsomes are increased by the process of potassium adaptation. We conclude that skeletal muscle is an important participant in potassium adaptation and acts to temporarily buffer acute increases in the extracellular concentration of potassium.

  8. Electrolytic coloration below 100 °C and spectral properties of potassium alum crystals

    NASA Astrophysics Data System (ADS)

    Gu, Hongen; Li, Yutong

    2015-03-01

    Potassium alum crystals are colored electrolytically below 100 °C and under various voltages using a pointed cathode and a flat anode. SO3-, SO2-, O3-, O2-, O- hole-trapped centers and O0, O2-, H+ radicals are produced in colored potassium alum crystals. No obvious characteristic absorption band in ultraviolet and visible wavelength regions is observed in absorption spectrum of uncolored potassium alum crystal. Characteristic absorption bands of SO3-, SO2- and O3- hole-trapped centers are observed in the absorption spectra of the colored potassium alum crystals. The hole-trapped centers and radicals come from electric- and thermal-induced decomposition of SO42- radicals and crystalline water molecules. Current-time curve for electrolytic coloration of potassium alum crystal is given. Electron exchanges from electrons and small charged radicals to electrodes induce complete current.

  9. Electrolytic coloration below 100°C and spectral properties of potassium alum crystals.

    PubMed

    Gu, Hongen; Li, Yutong

    2015-03-15

    Potassium alum crystals are colored electrolytically below 100°C and under various voltages using a pointed cathode and a flat anode. SO3(-), SO2(-), O3(-), O2(-), O(-) hole-trapped centers and O(0), O(2-), H(+) radicals are produced in colored potassium alum crystals. No obvious characteristic absorption band in ultraviolet and visible wavelength regions is observed in absorption spectrum of uncolored potassium alum crystal. Characteristic absorption bands of SO3(-), SO2(-) and O3(-) hole-trapped centers are observed in the absorption spectra of the colored potassium alum crystals. The hole-trapped centers and radicals come from electric- and thermal-induced decomposition of SO4(2-) radicals and crystalline water molecules. Current-time curve for electrolytic coloration of potassium alum crystal is given. Electron exchanges from electrons and small charged radicals to electrodes induce complete current. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. High potassium intake blunts the effect of elevated sodium intake on blood pressure levels.

    PubMed

    Rodrigues, Sérgio Lamêgo; Baldo, Marcelo Perim; Machado, Rebeca Caldeira; Forechi, Ludimila; Molina, Maria del Carmem Bisi; Mill, José Geraldo

    2014-04-01

    The purpose of this study was to investigate the influence of dietary potassium on the sodium effect on blood pressure (BP) in the general population and the adherence of current recommendations for sodium and potassium intake. An overnight (12-hour) urine sample was collected in a population-based study to investigate cardiovascular risk. A sub-sample of 1285 subjects (age range, 25-64 years) free from any medication interfering with BP or potassium excretion was studied. Of the participants, 86.0% consumed over 6 g of salt/day and 87.7% less than the recommended intake of potassium (4.7 g). Potassium excretion and the sodium to potassium ratio were significantly related to systolic and diastolic BP only in subjects consuming more than 6 g/day of salt. Subjects in the highest sodium to potassium ratio quartile (surrogate of unhealthy diet) presented 8 mm Hg and 7 mm Hg higher values of systolic and diastolic BP, respectively, when compared with the first quartile, while individuals in the fourth quartile of urinary potassium excretion (healthier diet) showed 6 mm Hg and 4 mm Hg lower systolic and diastolic BP, respectively, compared with the first quartile. Our data indicate that when people have an increased intake of potassium, high intake of sodium is not associated with higher BP.

  11. The effects of potassium depletion and supplementation on blood pressure: a clinical review.

    PubMed

    Barri, Y M; Wingo, C S

    1997-07-01

    Nonpharmacologic treatment currently is recognized as an important part in the treatment of hypertension, and the role of dietary potassium intake in blood pressure (BP) control is becoming quite evident. Clinical studies have examined the mechanism by which hypokalemia can increase BP and the benefit of a large potassium intake on BP control. Epidemiologic data suggest that potassium intake and BP are correlated inversely. In normotensive subjects, those who are salt sensitive or who have a family history of hypertension appear to benefit most from the hypotensive effects of potassium supplementation. The greatest hypotensive effect of potassium supplementation occurs in patients with severe hypertension. This effect is pronounced with prolonged potassium supplementation. The antihypertensive effect of increased potassium intake appears to be mediated by several factors, which include enhancing natriuresis, modulating baroreflex sensitivity, direct vasodilation, or lowering cardiovascular reactivity to norepinephrine or angiotensin II. Potassium repletion in patients with diuretic-induced hypokalemia improves BP control. An increase in potassium intake should be included in the nonpharmacologic management of patients with uncomplicated hypertension.

  12. Sodium and chloride transport in the large intestine of potassium-loaded rats

    SciTech Connect

    Budinger, M.E.; Foster, E.S.; Hayslett, J.P.; Binder, H.J.

    1986-08-01

    Increased dietary potassium (potassium loading) induces several adaptive changes in colonic function, including increased potential dependent potassium secretion, active potassium secretion, and Na-K-ATPase activity, but does not alter net sodium absorption in vivo. To establish whether potassium loading stimulates active sodium transport, unidirectional, net sodium, and chloride fluxes were determined under voltage-clamp conditions across isolated rat distal colonic mucosa. In normal animals net sodium flux (J/sub net/sup Na/), net chloride flux (J/sub net/sub Cl/) and short-circuit current (I/sub sc/) were 6.1 +/- 1.1, 8.4 +/-1.0, and 0.7 +/- 0.1 eq h cm S, respectively; potassium loading significantly increased J/sub net/sup Na/ and I/sup sc/ by 4.9 +/- 1.4 and 3.5 +/- 0.7 eq h cm S, respectively, without changing J/sub net/sup Na/ and I/sub sc/ produced by potassium loading. In Cl-free Ringer solution in normal animals J/sub net/sup Na was reduced to 0.6 +/- 0.3 eq h cm S. Potassium loading produced identical increases in J/sub net/sup Na/ and I/sub sc/, which were also completely inhibited by 0.1 mM amiloride. These studies establish that potassium loading induces amiloride-sensitive electrogenic sodium absorption without affecting electroneutral sodium-chloride absorption.

  13. Role of Circadian Rhythms in Potassium Homeostasis

    PubMed Central

    Gumz, Michelle L.; Rabinowitz, Lawrence

    2013-01-01

    It has been known for decades that urinary potassium excretion varies with a circadian pattern. In this review, we consider the historical evidence for this phenomenon and present an overview of recent developments in the field. Extensive evidence from the latter part of the last century clearly demonstrates that circadian potassium excretion does not depend on endogenous aldosterone. Of note is the recent discovery that the expression of several renal potassium transporters varies with a circadian pattern that appears to be consistent with substantial clinical data regarding daily fluctuations in urinary potassium levels. We propose the circadian clock mechanism as a key regulator of renal potassium transporters, and consequently renal potassium excretion. Further investigation into the mechanism of regulation of renal potassium transport by the circadian clock is warranted in order to increase our understanding of the clinical relevance of circadian rhythms to potassium homeostasis. PMID:23953800

  14. Can Diuretics Decrease Your Potassium Level?

    MedlinePlus

    Diseases and Conditions High blood pressure (hypertension) Can diuretics decrease your potassium level? Answers from Sheldon G. Sheps, M.D. Yes, some diuretics — also called water pills — decrease potassium in the ...

  15. 21 CFR 172.730 - Potassium bromate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ....730 Potassium bromate. The food additive potassium bromate may be safely used in the malting of barley... barley under conditions whereby the amount of the additive present in the malt from the treatment...

  16. The relation of potassium and sodium intakes to diet cost among US adults

    PubMed Central

    Drewnowski, Adam; Rehm, Colin D; Maillot, Matthieu; Monsivais, Pablo

    2014-01-01

    The 2010 Dietary Guidelines recommended that Americans increase potassium and decrease sodium intakes to reduce the burden of hypertension. One reason why so few Americans meet the recommended potassium or sodium goals may be perceived or actual food costs. This study explored the monetary costs associated with potassium and sodium intakes using national food prices and a representative sample of US adults. Dietary intake data from the 2001-2002 National Health and Nutrition Examination Survey were merged with a national food prices database. In a population of 4,744 adults, the association between the energy-adjusted sodium and potassium intakes and the sodium-to-potassium ratio (Na:K), and energy-adjusted diet cost was evaluated. Diets that were more potassium-rich or had lower sodium-potassium ratios were associated with higher diet costs, while sodium intakes were not related to cost. The difference in diet cost among participants with highest and lowest potassium intakes was $1.49 (95% CI 1.29, 1.69). A food-level analysis showed that beans, potatoes, coffee, milk, bananas, citrus juices and carrots are frequently consumed and low-cost sources of potassium. Based on existing dietary data and current American eating habits, a potassium-dense diet was associated with higher diet costs, while sodium was not. Price interventions may be an effective approach to improve potassium intakes and reduce the Na:K ratio of the diet. The present methods helped identify some alternative low-cost foods that were effective in increasing potassium intakes. The identification and promotion of lower-cost foods to help individuals meet targeted dietary recommendations could accompany future dietary guidelines. PMID:24871907

  17. Membrane currents of spiking cells isolated from turtle retina.

    PubMed

    Lasater, E M; Witkovsky, P

    1990-05-01

    We examined the membrane properties of spiking neurons isolated from the turtle (Pseudemys scripta) retina. The cells were maintained in culture for 1-7 days and were studied with the whole cell patch clamp technique. We utilized cells whose perikaryal diameters were greater than 15 microns since Kolb (1982) reported that ganglion cell perikarya in Pseudemys retina are 13-25 microns, whereas amacrine perikarya are less than 14 microns in diameter. We identified 5 currents in the studied cells: (1) a transient sodium current (INa) blocked by TTX, (2) a sustained calcium current (ICa) blocked by cobalt and enhanced by Bay-K 8644, (3) a calcium-dependent potassium current (IK(Ca)), (4) an A-type transient potassium current (IA) somewhat more sensitive to 4-AP than TEA, (5) a sustained potassium current (IK) more sensitive to TEA than 4-AP. The estimated average input resistance of the cells at -70 mV was 720 +/- 440 M omega. When all active currents were blocked, the membrane resistance between -130 and +20 mV was 2.5 G omega. When examined under current clamp, some cells produced multiple spikes to depolarizing steps of 0.1-0.3 nA, whereas other cells produced only a single spike irrespective of the strength of the current pulse. Most single spikers had an outward current that rose to a peak relatively slowly, whereas multiple spikers tend to have a more rapidly activating outward current. Under current clamp, 4-AP slowed the repolarization phase of the spike thus broadening it, but did not always abolish the ability to produce multiple spikes. TEA induced a depolarized plateau following the initial spike which precluded further spikes. It thus appears that the spiking patterns of the retinal cells are shaped primarily by the kinetics of INa, IK and IA and to a lesser extent by IK(Ca).

  18. The Efflux of Potassium from Electroplaques of Electric Eels

    PubMed Central

    Whittam, R.; Guinnebault, M.

    1960-01-01

    1. The movement of labeled potassium ions has been measured across the innervated membranes of single isolated electroplaques, obtained from the organ of Sachs of Electrophorus electricus, mounted in an apparatus which allowed a separate washing of the two membranes. 2. Equations have been derived for a 3 compartment system in series in which tracer from a large pool in one outer compartment is collected in the other outer compartment. The amount of unlabeled ion in the middle compartment may be calculated and also the fluxes across the two membranes. 3. The flux of potassium across the innervated membranes of resting cells in a steady state was between 700 to 1000 µµmoles/cm.2/sec. and was unaffected by d-tubocurarine. 4. Direct stimulation of electroplaques with external electrodes caused an increase in the efflux of potassium from the innervated membrane of 5 to 8 µµmoles/cm.2/impulse, which was unaffected by d-tubocurarine; no change occurred in the efflux across the non-innervated membrane. 5. It is concluded that the discharge of electroplaques is accompanied by a small outward movement of potassium ions across the innervated membrane of the same order of magnitude as that found on excitation of squid giant axons. The data show a basic similarity of potassium movements across these two entirely different types of conducting membranes and suggest that this phenomenon may be a general feature of bioelectric currents propagating an action potential. PMID:13784938

  19. [Physical exercise and serum potassium in renal insufficiency].

    PubMed

    Lens, X M; Oliva, J A; Codinach, P; Pascual, R; Carrió, J; Mallafré, J M

    1989-04-01

    In order to study the effect of physical exercise on serum potassium in renal failure, twelve patients currently on chronic dialysis were subjected to physical exercise by means of an ergometric bicycle. The initial serum potassium was 5.2 +/- 0.6 mmol/l and after the performance of 3.304 +/- 1.583 kilopondimeters of total work, serum potassium was not modified: 5.5 +/- 0.6 mmol/l (p = NS). With regard to the parameters that regulate the intra-cellular distribution of serum potassium, physical exercise aggravated metabolic acidosis, decreasing the blood pH: from 7.33 +/- 0.05 to 7.23 +/- 0.08 (p less than 0.01) and plasma bicarbonate: from 19 +/- 3 mmol/l to 14 +/- 4 mmol/l (p less than 0.01); this was accompanied by a significant and percentage-wise similar increase in plasma epinephrine and norepinephrine. Patients with end-stage renal failure can perform moderate physical exercise, since this does not produce significant changes in serum potassium.

  20. 21 CFR 184.1625 - Potassium citrate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Potassium citrate. 184.1625 Section 184.1625 Food... Specific Substances Affirmed as GRAS § 184.1625 Potassium citrate. (a) Potassium citrate (C6H5K3O7·H2O, CAS Reg. No. 006100-0905-096) is the potassium salt of citric acid. It is prepared by neutralizing citric...

  1. 21 CFR 184.1639 - Potassium lactate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Potassium lactate. 184.1639 Section 184.1639 Food... Specific Substances Affirmed as GRAS § 184.1639 Potassium lactate. (a) Potassium lactate (C3H5O3K, CAS Reg. No. 996-31-6) is the potassium salt of lactic acid. It is a hydroscopic, white, odorless solid and is...

  2. 21 CFR 184.1625 - Potassium citrate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Potassium citrate. 184.1625 Section 184.1625 Food... Specific Substances Affirmed as GRAS § 184.1625 Potassium citrate. (a) Potassium citrate (C6H5K3O7·H2O, CAS Reg. No. 006100-0905-096) is the potassium salt of citric acid. It is prepared by neutralizing citric...

  3. 21 CFR 184.1639 - Potassium lactate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Potassium lactate. 184.1639 Section 184.1639 Food... Specific Substances Affirmed as GRAS § 184.1639 Potassium lactate. (a) Potassium lactate (C3H5O3K, CAS Reg. No. 996-31-6) is the potassium salt of lactic acid. It is a hydroscopic, white, odorless solid and is...

  4. 21 CFR 184.1625 - Potassium citrate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Potassium citrate. 184.1625 Section 184.1625 Food... Specific Substances Affirmed as GRAS § 184.1625 Potassium citrate. (a) Potassium citrate (C6H5K3O7·H2O, CAS Reg. No. 006100-0905-096) is the potassium salt of citric acid. It is prepared by neutralizing citric...

  5. 21 CFR 184.1639 - Potassium lactate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Potassium lactate. 184.1639 Section 184.1639 Food... GRAS § 184.1639 Potassium lactate. (a) Potassium lactate (C3H5O3K, CAS Reg. No. 996-31-6) is the potassium salt of lactic acid. It is a hydroscopic, white, odorless solid and is prepared commercially by...

  6. 21 CFR 184.1625 - Potassium citrate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Potassium citrate. 184.1625 Section 184.1625 Food... Specific Substances Affirmed as GRAS § 184.1625 Potassium citrate. (a) Potassium citrate (C6H5K3O7·H2O, CAS Reg. No. 006100-0905-096) is the potassium salt of citric acid. It is prepared by neutralizing citric...

  7. 21 CFR 184.1639 - Potassium lactate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Potassium lactate. 184.1639 Section 184.1639 Food... Specific Substances Affirmed as GRAS § 184.1639 Potassium lactate. (a) Potassium lactate (C3H5O3K, CAS Reg. No. 996-31-6) is the potassium salt of lactic acid. It is a hydroscopic, white, odorless solid and is...

  8. 21 CFR 184.1639 - Potassium lactate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Potassium lactate. 184.1639 Section 184.1639 Food... Specific Substances Affirmed as GRAS § 184.1639 Potassium lactate. (a) Potassium lactate (C3H5O3K, CAS Reg. No. 996-31-6) is the potassium salt of lactic acid. It is a hydroscopic, white, odorless solid and is...

  9. 21 CFR 182.3637 - Potassium metabisulfite.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Potassium metabisulfite. 182.3637 Section 182.3637 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD....3637 Potassium metabisulfite. (a) Product. Potassium metabisulfite. (b) [Reserved] (c) Limitations...

  10. 21 CFR 582.6625 - Potassium citrate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Potassium citrate. 582.6625 Section 582.6625 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Potassium citrate. (a) Product. Potassium citrate. (b) Conditions of use. This substance is generally...

  11. 21 CFR 182.3640 - Potassium sorbate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Potassium sorbate. 182.3640 Section 182.3640 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR... Potassium sorbate. (a) Product. Potassium sorbate. (b) Conditions of use. This substance is generally...

  12. 21 CFR 582.1643 - Potassium sulfate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Potassium sulfate. 582.1643 Section 582.1643 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1643 Potassium sulfate. (a) Product. Potassium sulfate. (b) Conditions of use. This...

  13. 21 CFR 582.1613 - Potassium bicarbonate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Potassium bicarbonate. 582.1613 Section 582.1613 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1613 Potassium bicarbonate. (a) Product. Potassium bicarbonate. (b) Conditions of use. This...

  14. 21 CFR 182.3637 - Potassium metabisulfite.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Potassium metabisulfite. 182.3637 Section 182.3637 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD....3637 Potassium metabisulfite. (a) Product. Potassium metabisulfite. (b) (c) Limitations, restrictions...

  15. 21 CFR 182.3637 - Potassium metabisulfite.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Potassium metabisulfite. 182.3637 Section 182.3637 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD....3637 Potassium metabisulfite. (a) Product. Potassium metabisulfite. (b) (c) Limitations, restrictions...

  16. 21 CFR 172.160 - Potassium nitrate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Potassium nitrate. 172.160 Section 172.160 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR... Food Preservatives § 172.160 Potassium nitrate. The food additive potassium nitrate may be safely used...

  17. 21 CFR 182.3637 - Potassium metabisulfite.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Potassium metabisulfite. 182.3637 Section 182.3637...) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Chemical Preservatives § 182.3637 Potassium metabisulfite. (a) Product. Potassium metabisulfite. (b) (c) Limitations, restrictions, or explanation. This substance is...

  18. 21 CFR 182.3637 - Potassium metabisulfite.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Potassium metabisulfite. 182.3637 Section 182.3637 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD....3637 Potassium metabisulfite. (a) Product. Potassium metabisulfite. (b) (c) Limitations, restrictions...

  19. 21 CFR 582.1625 - Potassium citrate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Potassium citrate. 582.1625 Section 582.1625 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1625 Potassium citrate. (a) Product. Potassium citrate. (b) Conditions of use. This...

  20. 21 CFR 582.6625 - Potassium citrate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Potassium citrate. 582.6625 Section 582.6625 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Potassium citrate. (a) Product. Potassium citrate. (b) Conditions of use. This substance is generally...

  1. 21 CFR 172.160 - Potassium nitrate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Potassium nitrate. 172.160 Section 172.160 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR... Food Preservatives § 172.160 Potassium nitrate. The food additive potassium nitrate may be safely used...

  2. 21 CFR 582.5634 - Potassium iodide.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Potassium iodide. 582.5634 Section 582.5634 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Supplements 1 § 582.5634 Potassium iodide. (a) Product. Potassium iodide. (b) Tolerance. 0.01 percent. (c...

  3. 21 CFR 582.1619 - Potassium carbonate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Potassium carbonate. 582.1619 Section 582.1619 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1619 Potassium carbonate. (a) Product. Potassium carbonate. (b) Conditions of use. This...

  4. 21 CFR 182.3640 - Potassium sorbate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Potassium sorbate. 182.3640 Section 182.3640 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Chemical Preservatives § 182.3640 Potassium sorbate. (a) Product. Potassium...

  5. 21 CFR 582.1619 - Potassium carbonate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Potassium carbonate. 582.1619 Section 582.1619 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1619 Potassium carbonate. (a) Product. Potassium carbonate. (b) Conditions of use. This...

  6. 75 FR 51112 - Potassium Permanganate From China

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-18

    ... COMMISSION Potassium Permanganate From China AGENCY: United States International Trade Commission. ACTION: Scheduling of an expedited five-year review concerning the antidumping duty order on potassium permanganate... whether revocation of the antidumping duty order on potassium permanganate from China would be likely to...

  7. 21 CFR 582.1625 - Potassium citrate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Potassium citrate. 582.1625 Section 582.1625 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1625 Potassium citrate. (a) Product. Potassium citrate. (b) Conditions of use. This...

  8. 21 CFR 582.3640 - Potassium sorbate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Potassium sorbate. 582.3640 Section 582.3640 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL....3640 Potassium sorbate. (a) Product. Potassium sorbate. (b) Conditions of use. This substance is...

  9. 21 CFR 582.1619 - Potassium carbonate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Potassium carbonate. 582.1619 Section 582.1619 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1619 Potassium carbonate. (a) Product. Potassium carbonate. (b) Conditions of use. This...

  10. 21 CFR 172.160 - Potassium nitrate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Potassium nitrate. 172.160 Section 172.160 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN... Preservatives § 172.160 Potassium nitrate. The food additive potassium nitrate may be safely used as a curing...

  11. 21 CFR 582.5622 - Potassium chloride.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Potassium chloride. 582.5622 Section 582.5622 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Supplements 1 § 582.5622 Potassium chloride. (a) Product. Potassium chloride. (b) Conditions of use. This...

  12. 21 CFR 582.5622 - Potassium chloride.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Potassium chloride. 582.5622 Section 582.5622 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Supplements 1 § 582.5622 Potassium chloride. (a) Product. Potassium chloride. (b) Conditions of use. This...

  13. 21 CFR 582.1613 - Potassium bicarbonate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Potassium bicarbonate. 582.1613 Section 582.1613 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1613 Potassium bicarbonate. (a) Product. Potassium bicarbonate. (b) Conditions of use. This...

  14. 21 CFR 182.3616 - Potassium bisulfite.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Potassium bisulfite. 182.3616 Section 182.3616 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD....3616 Potassium bisulfite. (a) Product. Potassium bisulfite. (b) (c) Limitations, restrictions, or...

  15. 21 CFR 582.7610 - Potassium alginate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Potassium alginate. 582.7610 Section 582.7610 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Potassium alginate. (a) Product. Potassium alginate. (b) Conditions of use. This substance is generally...

  16. 21 CFR 582.3616 - Potassium bisulfite.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Potassium bisulfite. 582.3616 Section 582.3616 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL....3616 Potassium bisulfite. (a) Product. Potassium bisulfite. (b) [Reserved] (c) Limitations...

  17. 21 CFR 582.5634 - Potassium iodide.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Potassium iodide. 582.5634 Section 582.5634 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Supplements 1 § 582.5634 Potassium iodide. (a) Product. Potassium iodide. (b) Tolerance. 0.01 percent. (c...

  18. 21 CFR 582.1613 - Potassium bicarbonate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Potassium bicarbonate. 582.1613 Section 582.1613 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1613 Potassium bicarbonate. (a) Product. Potassium bicarbonate. (b) Conditions of use. This...

  19. 21 CFR 582.1631 - Potassium hydroxide.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Potassium hydroxide. 582.1631 Section 582.1631 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1631 Potassium hydroxide. (a) Product. Potassium hydroxide. (b) Conditions of use. This...

  20. 21 CFR 582.6625 - Potassium citrate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Potassium citrate. 582.6625 Section 582.6625 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Potassium citrate. (a) Product. Potassium citrate. (b) Conditions of use. This substance is generally...

  1. 21 CFR 582.3637 - Potassium metabisulfite.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Potassium metabisulfite. 582.3637 Section 582.3637 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL....3637 Potassium metabisulfite. (a) Product. Potassium metabisulfite. (b) [Reserved] (c) Limitations...

  2. 21 CFR 182.3640 - Potassium sorbate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Potassium sorbate. 182.3640 Section 182.3640 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR... Potassium sorbate. (a) Product. Potassium sorbate. (b) Conditions of use. This substance is generally...

  3. 21 CFR 582.3637 - Potassium metabisulfite.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Potassium metabisulfite. 582.3637 Section 582.3637 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL....3637 Potassium metabisulfite. (a) Product. Potassium metabisulfite. (b) (c) Limitations, restrictions...

  4. 21 CFR 582.1613 - Potassium bicarbonate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Potassium bicarbonate. 582.1613 Section 582.1613 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1613 Potassium bicarbonate. (a) Product. Potassium bicarbonate. (b) Conditions of use. This...

  5. 21 CFR 582.3616 - Potassium bisulfite.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Potassium bisulfite. 582.3616 Section 582.3616 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL....3616 Potassium bisulfite. (a) Product. Potassium bisulfite. (b) (c) Limitations, restrictions, or...

  6. 21 CFR 172.160 - Potassium nitrate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Potassium nitrate. 172.160 Section 172.160 Food... ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION Food Preservatives § 172.160 Potassium nitrate. The food additive potassium nitrate may be safely used as a curing agent in the processing of cod...

  7. 21 CFR 582.6625 - Potassium citrate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Potassium citrate. 582.6625 Section 582.6625 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Potassium citrate. (a) Product. Potassium citrate. (b) Conditions of use. This substance is generally...

  8. 21 CFR 582.5634 - Potassium iodide.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Potassium iodide. 582.5634 Section 582.5634 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Supplements 1 § 582.5634 Potassium iodide. (a) Product. Potassium iodide. (b) Tolerance. 0.01 percent. (c...

  9. 21 CFR 182.3616 - Potassium bisulfite.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Potassium bisulfite. 182.3616 Section 182.3616 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD....3616 Potassium bisulfite. (a) Product. Potassium bisulfite. (b) (c) Limitations, restrictions, or...

  10. 21 CFR 582.7610 - Potassium alginate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Potassium alginate. 582.7610 Section 582.7610 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Potassium alginate. (a) Product. Potassium alginate. (b) Conditions of use. This substance is generally...

  11. 21 CFR 582.5622 - Potassium chloride.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Potassium chloride. 582.5622 Section 582.5622 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Supplements 1 § 582.5622 Potassium chloride. (a) Product. Potassium chloride. (b) Conditions of use. This...

  12. 21 CFR 172.730 - Potassium bromate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Potassium bromate. 172.730 Section 172.730 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR... Other Specific Usage Additives § 172.730 Potassium bromate. The food additive potassium bromate may be...

  13. 21 CFR 182.3616 - Potassium bisulfite.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Potassium bisulfite. 182.3616 Section 182.3616...) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Chemical Preservatives § 182.3616 Potassium bisulfite. (a) Product. Potassium bisulfite. (b) (c) Limitations, restrictions, or explanation. This substance is generally...

  14. 21 CFR 582.1613 - Potassium bicarbonate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Potassium bicarbonate. 582.1613 Section 582.1613 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1613 Potassium bicarbonate. (a) Product. Potassium bicarbonate. (b) Conditions of use. This...

  15. 75 FR 23298 - Potassium Permanganate From China

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-03

    ... COMMISSION Potassium Permanganate From China AGENCY: United States International Trade Commission. ACTION: Institution of a five-year review concerning the antidumping duty order on potassium permanganate from China... antidumping duty order on potassium permanganate from China would be likely to lead to continuation or...

  16. 21 CFR 582.1619 - Potassium carbonate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Potassium carbonate. 582.1619 Section 582.1619 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1619 Potassium carbonate. (a) Product. Potassium carbonate. (b) Conditions of use. This...

  17. 21 CFR 582.3640 - Potassium sorbate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Potassium sorbate. 582.3640 Section 582.3640 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL....3640 Potassium sorbate. (a) Product. Potassium sorbate. (b) Conditions of use. This substance is...

  18. 21 CFR 582.1643 - Potassium sulfate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Potassium sulfate. 582.1643 Section 582.1643 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1643 Potassium sulfate. (a) Product. Potassium sulfate. (b) Conditions of use. This...

  19. 21 CFR 582.1625 - Potassium citrate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Potassium citrate. 582.1625 Section 582.1625 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1625 Potassium citrate. (a) Product. Potassium citrate. (b) Conditions of use. This...

  20. 21 CFR 182.3640 - Potassium sorbate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Potassium sorbate. 182.3640 Section 182.3640 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR... Potassium sorbate. (a) Product. Potassium sorbate. (b) Conditions of use. This substance is generally...

  1. 21 CFR 582.1643 - Potassium sulfate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Potassium sulfate. 582.1643 Section 582.1643 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1643 Potassium sulfate. (a) Product. Potassium sulfate. (b) Conditions of use. This...

  2. 21 CFR 582.1631 - Potassium hydroxide.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Potassium hydroxide. 582.1631 Section 582.1631 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1631 Potassium hydroxide. (a) Product. Potassium hydroxide. (b) Conditions of use. This...

  3. 21 CFR 582.5628 - Potassium glycerophosphate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Potassium glycerophosphate. 582.5628 Section 582.5628 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Dietary Supplements 1 § 582.5628 Potassium glycerophosphate. (a) Product. Potassium glycerophosphate. (b...

  4. 21 CFR 582.5628 - Potassium glycerophosphate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Potassium glycerophosphate. 582.5628 Section 582.5628 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Dietary Supplements 1 § 582.5628 Potassium glycerophosphate. (a) Product. Potassium glycerophosphate. (b...

  5. 21 CFR 582.7610 - Potassium alginate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Potassium alginate. 582.7610 Section 582.7610 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Potassium alginate. (a) Product. Potassium alginate. (b) Conditions of use. This substance is generally...

  6. 21 CFR 582.3640 - Potassium sorbate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Potassium sorbate. 582.3640 Section 582.3640 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL....3640 Potassium sorbate. (a) Product. Potassium sorbate. (b) Conditions of use. This substance is...

  7. 21 CFR 582.3616 - Potassium bisulfite.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Potassium bisulfite. 582.3616 Section 582.3616 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL....3616 Potassium bisulfite. (a) Product. Potassium bisulfite. (b) (c) Limitations, restrictions, or...

  8. 21 CFR 582.6625 - Potassium citrate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Potassium citrate. 582.6625 Section 582.6625 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Potassium citrate. (a) Product. Potassium citrate. (b) Conditions of use. This substance is generally...

  9. 21 CFR 582.7610 - Potassium alginate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Potassium alginate. 582.7610 Section 582.7610 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Potassium alginate. (a) Product. Potassium alginate. (b) Conditions of use. This substance is generally...

  10. 21 CFR 182.3640 - Potassium sorbate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Potassium sorbate. 182.3640 Section 182.3640 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR... Potassium sorbate. (a) Product. Potassium sorbate. (b) Conditions of use. This substance is generally...

  11. 21 CFR 582.3616 - Potassium bisulfite.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Potassium bisulfite. 582.3616 Section 582.3616 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL....3616 Potassium bisulfite. (a) Product. Potassium bisulfite. (b) (c) Limitations, restrictions, or...

  12. 21 CFR 582.5622 - Potassium chloride.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Potassium chloride. 582.5622 Section 582.5622 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Supplements 1 § 582.5622 Potassium chloride. (a) Product. Potassium chloride. (b) Conditions of use. This...

  13. 21 CFR 201.72 - Potassium labeling.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 4 2012-04-01 2012-04-01 false Potassium labeling. 201.72 Section 201.72 Food and... LABELING Labeling Requirements for Over-the-Counter Drugs § 201.72 Potassium labeling. (a) The labeling of over-the-counter (OTC) drug products intended for oral ingestion shall contain the potassium content...

  14. 21 CFR 582.3637 - Potassium metabisulfite.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Potassium metabisulfite. 582.3637 Section 582.3637 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL....3637 Potassium metabisulfite. (a) Product. Potassium metabisulfite. (b) (c) Limitations, restrictions...

  15. 21 CFR 582.1631 - Potassium hydroxide.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Potassium hydroxide. 582.1631 Section 582.1631 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1631 Potassium hydroxide. (a) Product. Potassium hydroxide. (b) Conditions of use. This...

  16. 21 CFR 582.7610 - Potassium alginate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Potassium alginate. 582.7610 Section 582.7610 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Potassium alginate. (a) Product. Potassium alginate. (b) Conditions of use. This substance is generally...

  17. 21 CFR 582.5622 - Potassium chloride.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Potassium chloride. 582.5622 Section 582.5622 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Supplements 1 § 582.5622 Potassium chloride. (a) Product. Potassium chloride. (b) Conditions of use. This...

  18. 21 CFR 582.5628 - Potassium glycerophosphate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Potassium glycerophosphate. 582.5628 Section 582.5628 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Dietary Supplements 1 § 582.5628 Potassium glycerophosphate. (a) Product. Potassium glycerophosphate. (b...

  19. 21 CFR 201.72 - Potassium labeling.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 4 2014-04-01 2014-04-01 false Potassium labeling. 201.72 Section 201.72 Food and... LABELING Labeling Requirements for Over-the-Counter Drugs § 201.72 Potassium labeling. (a) The labeling of over-the-counter (OTC) drug products intended for oral ingestion shall contain the potassium content...

  20. 21 CFR 582.3640 - Potassium sorbate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Potassium sorbate. 582.3640 Section 582.3640 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL....3640 Potassium sorbate. (a) Product. Potassium sorbate. (b) Conditions of use. This substance is...

  1. 21 CFR 582.5634 - Potassium iodide.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Potassium iodide. 582.5634 Section 582.5634 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Supplements 1 § 582.5634 Potassium iodide. (a) Product. Potassium iodide. (b) Tolerance. 0.01 percent. (c...

  2. 21 CFR 182.3616 - Potassium bisulfite.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Potassium bisulfite. 182.3616 Section 182.3616 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR... Potassium bisulfite. (a) Product. Potassium bisulfite. (b) [Reserved] (c) Limitations, restrictions, or...

  3. 21 CFR 582.1625 - Potassium citrate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Potassium citrate. 582.1625 Section 582.1625 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1625 Potassium citrate. (a) Product. Potassium citrate. (b) Conditions of use. This...

  4. 21 CFR 582.5628 - Potassium glycerophosphate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Potassium glycerophosphate. 582.5628 Section 582.5628 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Dietary Supplements 1 § 582.5628 Potassium glycerophosphate. (a) Product. Potassium glycerophosphate. (b...

  5. 21 CFR 582.1643 - Potassium sulfate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Potassium sulfate. 582.1643 Section 582.1643 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1643 Potassium sulfate. (a) Product. Potassium sulfate. (b) Conditions of use. This...

  6. 21 CFR 582.1631 - Potassium hydroxide.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Potassium hydroxide. 582.1631 Section 582.1631 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1631 Potassium hydroxide. (a) Product. Potassium hydroxide. (b) Conditions of use. This...

  7. 21 CFR 182.3616 - Potassium bisulfite.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Potassium bisulfite. 182.3616 Section 182.3616 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD....3616 Potassium bisulfite. (a) Product. Potassium bisulfite. (b) (c) Limitations, restrictions, or...

  8. 21 CFR 582.3616 - Potassium bisulfite.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Potassium bisulfite. 582.3616 Section 582.3616 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL....3616 Potassium bisulfite. (a) Product. Potassium bisulfite. (b) (c) Limitations, restrictions, or...

  9. 21 CFR 201.72 - Potassium labeling.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 4 2013-04-01 2013-04-01 false Potassium labeling. 201.72 Section 201.72 Food and... LABELING Labeling Requirements for Over-the-Counter Drugs § 201.72 Potassium labeling. (a) The labeling of over-the-counter (OTC) drug products intended for oral ingestion shall contain the potassium content...

  10. 21 CFR 582.1643 - Potassium sulfate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Potassium sulfate. 582.1643 Section 582.1643 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1643 Potassium sulfate. (a) Product. Potassium sulfate. (b) Conditions of use. This...

  11. 21 CFR 172.160 - Potassium nitrate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Potassium nitrate. 172.160 Section 172.160 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR... Food Preservatives § 172.160 Potassium nitrate. The food additive potassium nitrate may be safely used...

  12. 21 CFR 582.1619 - Potassium carbonate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Potassium carbonate. 582.1619 Section 582.1619 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1619 Potassium carbonate. (a) Product. Potassium carbonate. (b) Conditions of use. This...

  13. 21 CFR 582.5628 - Potassium glycerophosphate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Potassium glycerophosphate. 582.5628 Section 582.5628 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Dietary Supplements 1 § 582.5628 Potassium glycerophosphate. (a) Product. Potassium glycerophosphate. (b...

  14. 21 CFR 582.3637 - Potassium metabisulfite.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Potassium metabisulfite. 582.3637 Section 582.3637 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL....3637 Potassium metabisulfite. (a) Product. Potassium metabisulfite. (b) (c) Limitations, restrictions...

  15. 21 CFR 582.5634 - Potassium iodide.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Potassium iodide. 582.5634 Section 582.5634 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Supplements 1 § 582.5634 Potassium iodide. (a) Product. Potassium iodide. (b) Tolerance. 0.01 percent. (c...

  16. 21 CFR 582.3640 - Potassium sorbate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Potassium sorbate. 582.3640 Section 582.3640 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL....3640 Potassium sorbate. (a) Product. Potassium sorbate. (b) Conditions of use. This substance is...

  17. 21 CFR 582.1631 - Potassium hydroxide.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Potassium hydroxide. 582.1631 Section 582.1631 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1631 Potassium hydroxide. (a) Product. Potassium hydroxide. (b) Conditions of use. This...

  18. 21 CFR 582.1625 - Potassium citrate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Potassium citrate. 582.1625 Section 582.1625 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1625 Potassium citrate. (a) Product. Potassium citrate. (b) Conditions of use. This...

  19. 21 CFR 582.3637 - Potassium metabisulfite.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Potassium metabisulfite. 582.3637 Section 582.3637 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL....3637 Potassium metabisulfite. (a) Product. Potassium metabisulfite. (b) (c) Limitations, restrictions...

  20. 21 CFR 201.72 - Potassium labeling.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 4 2011-04-01 2011-04-01 false Potassium labeling. 201.72 Section 201.72 Food and... LABELING Labeling Requirements for Over-the-Counter Drugs § 201.72 Potassium labeling. (a) The labeling of over-the-counter (OTC) drug products intended for oral ingestion shall contain the potassium...