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PubMed2001

Distinct roles of CaMKII and PKA in regulation of firing patterns and K(+) currents in Drosophila neurons.

The Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and the cAMP-dependent protein kinase A (PKA) cascades have been implicated in neural mechanisms underlying learning and memory as supported by mutational analyses of the two enzymes in Drosophila. While there is mounting evidence for their roles in synaptic plasticity, less attention has been directed toward their regulation of neuronal membrane excitability and spike information coding. Here we report genetic and pharmacological analyses of the roles of PKA and CaMKII in the firing patterns and underlying K(+) currents in cultured Drosophila central neurons. Genetic perturbation of the catalytic subunit of PKA (DC0) did not alter the action potential duration but disrupted the frequency coding of spike-train responses to constant current injection in a subpopulation of neurons. In contrast, selective inhibition of CaMKII by the expression of an inhibitory peptide in ala transformants prolonged the spike duration but did not affect the spike frequency coding. Enhanced membrane excitability, indicated by spontaneous bursts of spikes, was observed in CaMKII-inhibited but not in PKA-diminished neurons. In wild-type neurons, the spike train firing patterns were highly reproducible under consistent stimulus conditions. However, disruption of either of these kinase pathways led to variable firing patterns in response to identical current stimuli delivered at a low frequency. Such variability in spike duration and frequency coding may impose problems for precision in signal processing in these protein kinase learning mutants. Pharmacological analyses of mutations that affect specific K(+) channel subunits demonstrated distinct effects of PKA and CaMKII in modulation of the kinetics and amplitude of different K(+) currents. The results suggest that PKA modulates Shaker A-type currents, whereas CaMKII modulates Shal-A type currents plus delayed rectifier Shab currents. Thus differential regulation of K(+) channels may influence the signal handling capability of neurons. This study provides support for the notion that, in addition to synaptic mechanisms, modulations in spike activity patterns may represent an important mechanism for learning and memory that should be explored more fully.

Action Potentials↗
PubMed2001

Distinct gene-specific mechanisms of arrhythmia revealed by cardiac gene transfer of two long QT disease genes, HERG and KCNE1.

The long QT syndrome (LQTS) is a heritable disorder that predisposes to sudden cardiac death. LQTS is caused by mutations in ion channel genes including HERG and KCNE1, but the precise mechanisms remain unclear. To clarify this situation we injected adenoviral vectors expressing wild-type or LQT mutants of HERG and KCNE1 into guinea pig myocardium. End points at 48-72 h included electrophysiology in isolated myocytes and electrocardiography in vivo. HERG increased the rapid component, I(Kr), of the delayed rectifier current, thereby accelerating repolarization, increasing refractoriness, and diminishing beat-to-beat action potential variability. Conversely, HERG-G628S suppressed I(Kr) without significantly delaying repolarization. Nevertheless, HERG-G628S abbreviated refractoriness and increased beat-to-beat variability, leading to early afterdepolarizations (EADs). KCNE1 increased the slow component of the delayed rectifier, I(Ks), without clear phenotypic sequelae. In contrast, KCNE1-D76N suppressed I(Ks) and markedly slowed repolarization, leading to frequent EADs and electrocardiographic QT prolongation. Thus, the two genes predispose to sudden death by distinct mechanisms: the KCNE1 mutant flagrantly undermines cardiac repolarization, and HERG-G628S subtly facilitates the genesis and propagation of premature beats. Our ability to produce electrocardiographic long QT in vivo with a clinical KCNE1 mutation demonstrates the utility of somatic gene transfer in creating genotype-specific disease models.

Action Potentials↗
PubMed1991

Role of calcium and protein kinase C in development of the delayed rectifier potassium current in Xenopus spinal neurons.

The delayed rectifier current of embryonic Xenopus spinal neurons plays the central role in developmental conversion of calcium-dependent action potentials to sodium-dependent spikes. During its maturation, this potassium current undergoes a pronounced increase in rate of activation. The mechanism underlying the change in kinetics was analyzed with whole-cell voltage clamp of neurons cultured under various conditions. Calcium is necessary at an early stage of development, to permit influx that triggers subsequent release of calcium from intracellular stores. Its action is prevented by depletion of protein kinase C and mimicked by stimulation of the kinase. Calcium influx through voltage-dependent channels at early stages of development regulates the differentiation of potassium current kinetics and modulation of the ionic dependence of action potentials.

Animals↗
PubMed2002

Electrophysiological properties of rainbow trout cardiac myocytes in serum-free primary culture.

A low-density primary culture of trout ventricular myocytes in serum-free growth medium was established and maintained for up to 10 days at 17 degrees C. The myocytes retained their normal rod shaped morphology, capacitive surface area of the sarcolemma (SL), and contractile quiescence. However, sarcolemmal cation currents changed significantly, some permanently, some transiently, after 8-10 days of culture. TTX-sensitive sodium current (I(Na)) and Ba(2+)-sensitive background inward rectifier potassium current (I(K1)) were permanently depressed to 24-28% of their control density measured in freshly isolated myocytes. In contrast, L-type calcium current (I(Ca)) was only transiently downregulated; after 2-3 days in culture, the density of the current was 32% of the control and recovered to the control value after 8-10 days in culture. The changes in membrane currents were reflected in the shape of the action potential (AP). After 2-3 days in culture, maximal overshoot potential and resting potential were significantly reduced, and the durations of the AP at 50 and 90% repolarization were significantly increased. These changes became significantly more pronounced after 8-10 days of culture, with the exception of AP duration at 50% repolarization level. The shortening of the early plateau phase may reflect an additional change to an outward current, presumably the rapid component of the delayed rectifier (I(Kr)). Although the present findings indicate that fish cardiac myocytes can be maintained in serum-free primary culture for at least 10 days at 17 degrees C, some but not all of the electrophysiological characteristics of the myocytes change markedly during culture. The changes in ion currents were not due to loss of sarcolemmal membrane and therefore are likely to represent altered expression of cation currents as an adaptive response to culture conditions.

Action Potentials↗
PubMed2000

Selective phenylalkylamine block of I(Kr) over other K(+) currents in guinea-pig ventricular myocytes.

Previous studies on verapamil and D600 have established that the Ca(2+)-channel blockers also inhibit delayed-rectifier K(+) currents in cardiac tissues and myocytes. However, estimated IC(50) values range over two to three orders of concentration, and it is unclear whether this reflects a high selectivity by one or both of the phenylalkylamines for particular K(+) channels. The purpose of the present study was to determine the concentration-dependent actions of verapamil and D600 on three defined cardiac K(+) currents. Guinea-pig ventricular myocytes in the conventional whole-cell configuration were bathed with normal Tyrode's or K(+)-free solution, and pulsed from -80 mV for measurement of the effects of 0.01 microM to 3 mM verapamil and D600 on the inwardly-rectifying K(+) current (I:(Kl)) and the two delayed-rectifier K(+) currents, rapidly-activating I:(Kr) and slowly-activating I:(Ks). The phenylalkylamines inhibited both inward- and outward-directed I:(Kl). The IC(50) values for outward I:(Kl) were approximately 220 microM. Verapamil and D600 were approximately equipotent inhibitors of the delayed-rectifier K(+) currents. They inhibited I:(Kr) with IC(50) near 3 microM, and I:(Ks) with IC(50) > or =280 microM. These results are discussed in relation to previous findings on K(+) currents and to the clinical actions of the drugs.

Animals↗
PubMed1995

Computer model of current-induced early afterdepolarizations in guinea pig ventricular myocytes.

We tested the ability of a computer model of transmembrane current and intracellular Ca2+ flux in the isolated guinea pig myocyte (Nordin, C., Am. J. Physiol. 265 (Heart Circ. Physiol. 34): H2117-H2136, 1993) to reproduce data from prior experimental studies and new data presented in this study regarding the behavior of early afterdepolarizations induced by constant inward current, a response closely related to the effect of localized injury currents in damaged myocardial syncytia. The goals of the study were to confirm the model's capacity to reproduce relevant experimental responses for which it was not originally designed and to analyze the mechanisms underlying the experimental phenomena. Under normal conditions, current-induced early afterdepolarizations in the model developed only from membrane potentials associated with L-type Ca2+ channel window current, and the magnitude of upstrokes was unaffected by blockade of either delayed rectifier K+ current or sarcoplasmic reticulum Ca2+ release. After Ca2+ loading secondary to either reduced extracellular [K+] or inhibition of Na(+)-K(+)-adenosinetriphosphatase activity, the threshold potential for current-induced early afterdepolarizations in the model, as with experimental myocytes, shifted to membrane potentials negative to the threshold potential for Ca2+ channel activation. Upstrokes were initiated by inward currents generated by electrogenic Na/Ca exchange following oscillatory Ca2+ release from the sarcoplasmic reticulum. New experiments presented in this study demonstrate that bursts of rapid depolarizing stimulations terminate current-induced early afterdepolarizations. Termination is caused by transient hyperpolarizations, which increase as a function of number or duration of stimulations, and if strong enough, cross the all-or-none threshold and lead to full repolarization. This experimental response was accurately simulated by the model through interactions that led to activation of delayed rectifier current, inactivation of Ca2+ channel current, and a reduction in inward Na/Ca exchange current secondary to altered intracellular Ca2+ cycling. We confirm that the model accurately simulates a wide range of responses beyond its original experimental constraints and suggest that current-induced early afterdepolarizations are initiated and terminated by complex processes that vary with specific experimental conditions and involve multiple currents.

Animals↗
PubMed1994

Chronic hypoxia is associated with reduced delayed rectifier K+ current in rat pulmonary artery muscle cells.

Pulmonary hypertension due to long-term hypoxia occurs as a result of both chronic obstructive pulmonary disease and habitation at high altitudes. Studies in animal models of chronic hypoxia have demonstrated the development of a persistent depolarization of pulmonary artery (PA) smooth muscle cells (SMCs). In seeking to explain this effect, we compared under normoxic conditions the K+ currents in SMCs isolated from small PA of chronically hypoxic and normoxic rats. Chronic hypoxia was associated with a marked (40-50%) reduction in amplitude of a K+ current, which had the pharmacological and kinetic characteristics of a delayed rectifier. The resting potential of the isolated PA cells from chronically hypoxic animals was significantly more positive (-43.5 +/- 2 mV) than that of cells from normoxic animals (-54.3 +/- 2 mV), and this depolarization could be approximately mimicked in the cells from normoxic animals by application of 1 mM 4-aminopyridine, a blocker of the delayed rectifier K+ current. Glibenclamide (1 microM), a blocker of ATP-sensitive K+ (KATP) channels, also caused a substantial (14.5 +/- 2.2 mV) depolarization of the membrane. These results suggest that both delayed rectifier and ATP-dependent K+ currents contribute to setting the membrane potential in these cells and are consistent with the possibility that downregulation of the delayed rectifier K+ current contributes to the depolarization and altered responsiveness to vasoactive agents of PAs that occurs during long-term hypoxia.

4-Aminopyridine↗
PubMed1998

Swelling-induced decrease in spontaneous pacemaker activity of rabbit isolated sino-atrial node cells.

The heart responds to an increase in sino-atrial node wall stress with an augmentation in rate of contraction. It has been suggested that swelling-activated ion channels may play a key role in that response. This paper investigates directly the effects of cell swelling on spontaneous activity of rabbit isolated sino-atrial node pacemaker cells. The main finding is that sino-atrial node cells, studied in current clamp mode using amphotericin-permeabilized patches, decrease their spontaneous pacemaker rate by 24.2 +/- 7.8% (P < 0.01, n = 9) during 75% hyposmotic swelling. This response is opposite to the predicted impact of volume-activation of sarcolemmal ion conductances. Computer modelling (OXSOFT Heart v4.8) suggests that swelling-induced dilution of the cytosol, reduction in intracellular potassium concentration, and decrease in the delayed rectifier potassium current, IK, are leading mechanisms in the response. This is supported by voltage-clamp data that show a swelling-induced positive shift in the reversal potential of IK by between 5 and 10 mV (n = 7) and a reduction in amplitude of its rapidly activating component, IKr, (n = 6). Thus, spontaneously active sino-atrial node cells reduce pacemaking rate during swelling. This response cannot be explained by the known volume-activated sarcolemmal ion conductances, but appears to be dictated by other mechanisms including dilution of the cytosol and reduction in IK. The results re-enforce the view that cardiac responses to cell volume changes may be quite different from those to longitudinal stretch.

Animals↗
PubMed2000

Suppression of maxi-K channel and membrane depolarization by synthetic polycations in single tracheal myocytes.

Polycationic proteins, e.g., major basic protein from eosinophils or cathepsin G from neutrophils, have been shown to increase nonspecific airway responsiveness. Along with several indirect manners of action, polycations were reported to contract smooth-muscle strips and to raise the cellular Ca(2+) concentration as a direct action on airway smooth muscle. However, the mechanistic basis for the direct behavior remains to be elucidated. To address this issue, we examined the effects of synthetic cationic polypeptides poly-L-arginine and poly-L-lysine on fresh single smooth-muscle cells from bovine trachea using a patch-clamp technique. Both of the polycations significantly depolarized the membrane from a baseline of about -40 to -20 mV in a dose-dependent manner. The polycations also suppressed whole-cell spontaneous transient outward currents as well as both the conductance (from a baseline of about 130 to 70 pS) and open-state probability (about 25% of control values) of large-conductance Ca(2+)-dependent K(+) channel (maxi-K channel) on excised outside-out patch membranes. The polycations were without effect on the whole-cell Ca(2+) currents induced by depolarizing voltage pulses. We concluded that the synthetic polycations had at least two sites of action; one is the delayed rectifier K(+) channel that is responsible for the membrane depolarization that increases Ca(2+) influx, and the other is the maxi-K channel the suppression of which inhibits muscle relaxation. These results may explain the direct contractile action and, therefore, one of the mechanisms underlying the airway hyperresponsiveness induced by various polycationic proteins.

Animals↗
PubMed2006

[Identification of E-4031-sensitive potassium current component in murine P19 embryonic carcinoma cell line differentiated in cardiomyocytes].

Pluripotent mouse P19 embryonic carcinoma cells represent a convenient in vitro model for studying various aspects of cardiac differentiation. Here by using whole-cell patch-clamp recording we have identified the rapid delayed rectifier K+ current, I(Kr) in P19 cell induced to differentiate into cardiac phenotype by DMSO (1%). Cardiac differentiation was confirmed by the appearance of spontaneously beating cells, their morphological features, ultrastructural clusterization of mitochondria around contraction elements, expression of cardiac actin mRNAs and MLC2v, and by the presence of inward sodium and calcium currents. I(Kr) was isolated based on the sensitivity to the specific blocker, E-4031, which at concentration of 1 MM blocked more than 50% of the total outward K+ current. However, in contrast to I(Kr) in native cardiac myocytes and in heterologous systems expressing I(Kr)-carrying ERG1 potassium channel, E-4031-sensitive K+ current in cardiac-like P19 cells lacked characteristic inward rectification, suggesting specific regulation and/or subunit composition of endogenous ERG -based channel in these cells. Establishing the reason(s) for this phenomenon will advance the understanding of the mechanisms of I(Kr)-channel rectification. Cardiac-differentiated P19 cells might also be useful for studying pharmacological modulation of I(Kr), which is recognized target for cardiotoxic side effects of numerous drugs.

Actins↗
PubMed1994

Mechanism of current-induced early afterdepolarizations in guinea pig ventricular myocytes.

We investigated possible ionic mechanisms that cause early afterdepolarizations (EADs) following the injection of constant inward current in guinea pig ventricular myocytes by several interventions that affect failure of action potential repolarization. The amount of constant current was adjusted to measure the threshold potential (Vth) associated with the minimum inward current required for inducing EADs [threshold current (Ith)] and also the magnitude of EADs at Vth and following adjustment of current to generate takeoff potentials of -30 and -20 mV. Interventions associated with either inhibition of Ca2+ release from the sarcoplasmic reticulum (ryanodine 5 x 10(-6) M) or L-type membrane Ca2+ channel current (verapamil 1.1 x 10(-5) M and nisoldipine 5 x 10(-7) M) reduced or abolished EADs arising from -30 or -20 mV. Cells that generated delayed afterdepolarizations (DADs) in the absence of depolarizing current after 20 stimulations at 5 Hz either in control solution or following interventions associated with Ca2+ loading (reduced extracellular [K+] or increased extracellular [Ca2+]) also developed a marked shift in Vth of current-induced EADs at 1-Hz stimulation to more negative potentials [60.3 +/- 10.7 mV (mean +/- SD, n = 17) vs. -41.7 +/- 6.4 mV in cells without DADs in control solution (n = 25), P < 0.001]. Ca2+ loading also increased the magnitude of EADs arising from Vth and -20 mV. Exposure to quinidine (1.23 x 10(-5) M), which blocks both Na+ and delayed rectifier K+ channels, significantly reduced Ith but had only minimal effect on the magnitude of EADs. Our results suggest that L-type Ca2+ channel current and [Ca2+]-sensitive inward current associated with release of Ca2+ from the sarcoplasmic reticulum are the major currents that cause this form of EADs, and that Ca2+ loading promotes the development of large EADs likely to propagate to normal tissue.

Action Potentials↗
PubMed1999

IA in Kenyon cells of the mushroom body of honeybees resembles shaker currents: kinetics, modulation by K+, and simulation.

Cultured Kenyon cells from the mushroom body of the honeybee, Apis mellifera, show a voltage-gated, fast transient K+ current that is sensitive to 4-aminopyridine, an A current. The kinetic properties of this A current and its modulation by extracellular K+ ions were investigated in vitro with the whole cell patch-clamp technique. The A current was isolated from other voltage-gated currents either pharmacologically or with suitable voltage-clamp protocols. Hodgkin- and Huxley-style mathematical equations were used for the description of this current and for the simulation of action potentials in a Kenyon cell model. Activation and inactivation of the A current are fast and voltage dependent with time constants of 0.4 +/- 0.1 ms (means +/- SE) at +45 mV and 3.0 +/- 1.6 ms at +45 mV, respectively. The pronounced voltage dependence of the inactivation kinetics indicates that at least a part of this current of the honeybee Kenyon cells is a shaker-like current. Deactivation and recovery from inactivation also show voltage dependency. The time constant of deactivation has a value of 0.4 +/- 0.1 ms at -75 mV. Recovery from inactivation needs a double-exponential function to be fitted adequately; the resulting time constants are 18 +/- 3.1 ms for the fast and 745 +/- 107 ms for the slow process at -75 mV. Half-maximal activation of the A current occurs at -0.7 +/- 2.9 mV, and half-maximal inactivation occurs at -54.7 +/- 2.4 mV. An increase in the extracellular K+ concentration increases the conductance and accelerates the recovery from inactivation of the A current, affecting the slow but not the fast time constant. With respect to these modulations the current under investigation resembles some of the shaker-like currents. The data of the A current were incorporated into a reduced computational model of the voltage-gated currents of Kenyon cells. In addition, the model contained a delayed rectifier K+ current, a Na+ current, and a leakage current. The model is able to generate an action potential on current injection. The model predicts that the A current causes repolarization of the action potential but not a delay in the initiation of the action potential. It further predicts that the activation of the delayed rectifier K+ current is too slow to contribute markedly to repolarization during a single action potential. Because of its fast activation, the A current reduces the amplitude of the net depolarizing current and thus reduces the peak amplitude and the duration of the action potential.

Action Potentials↗
PubMed1993

[Mechanisms involved in diversity of membrane excitability in smooth muscle cells].

Membrane ionic currents were recorded using whole cell and patch clamp techniques in smooth muscle cells isolated from various organs to clarify the mechanisms underlying the diversity of membrane excitability. Components of inward and outward currents upon depolarization were resolved from one another kinetically or pharmacologically and were analyzed and compared in these cells under the same conditions. Cells were isolated from the ureter (UT), urinary bladder (UB), vas deferens (VD), aorta (AT), pulmonary artery (PA), taenia caeci (TC) and ileum (IL) of the guinea pig; the femoral artery (FA), portal vein (PV) and iris sphincter (IS) of the rabbit; the stomach fundus (SF) of the rat; the trachea (TR) of the dog and the coronary artery (CA) of the pig. Action potentials were elicited by depolarization in cells from UT, UB, VD, TC, IL, SF and PV, but not in those from AT, PA, FA, IS, TR and CA. Currents identified included Ca2+ currents, Na+ current, Ca(2+)-dependent K+ current, two kinds of delayed rectifier K+ currents which were pharmacologically distinguished by sensitivity to 4-aminopyridine, and Ca(2+)-independent A-type transient K+ current. The membrane excitability including the action potential configuration in each cell type can be roughly explained by a combination of these currents, taking their amplitude and features into consideration.

Action Potentials↗
PubMed1997

Roles of outward potassium currents in the action potentials of guinea pig ureteral myocytes.

Outward currents of freshly dissociated ureteral myocytes consist mainly of Ca(2+)-activated K+ current (IKCa) and a transient outward current (ITO). No delayed rectifier current was apparent. IKCa is small and nondecaying and fluctuates actively and irregularly. Blocking IKCa decreased resting membrane conductance and prolonged action potential plateaus, showing its roles in maintaining the resting potential and in repolarizing action potentials. It is also responsible for the membrane potential fluctuations on action potential plateaus. Neither 8-(diethylamino)octyl-3,4,5-trimethoxybenzoate hydrochloride nor caffeine reduced the fluctuations in the outward current or in the action potentials, indicating that internal Ca2+ storage contributes little to the fluctuations. ITO has fast activation and inactivation kinetics with inactivation time constants of approximately 15 and 150 ms, respectively. Its highly negative voltage-availability relationship (V0.5 = -70.5 mV) suggests a low availability (< 5%) at normal resting potentials. It has only trivial effects on action potentials.

Action Potentials↗
PubMed2000

Interactions of the 5-hydroxytryptamine 3 antagonist class of antiemetic drugs with human cardiac ion channels.

Administration of the 5-hydroxytryptamine 3 receptor class of antiemetic agents has been associated with prolongation in the QRS, JT, and QT intervals of the ECG. To explore the mechanisms underlying these findings, we examined the effects of granisetron, ondansetron, dolasetron, and the active metabolite of dolasetron MDL 74,156 on the cloned human cardiac Na(+) channel hH1 and the human cardiac K(+) channel HERG and the slow delayed rectifier K(+) channel KvLQT1/minK. Using patch-clamp electrophysiology we found that all of the drugs blocked Na(+) channels in a frequency-dependent manner. At a frequency of 3 Hz, the IC(50) values for block of Na(+) current measured 2.6, 88.5, 38.0, and 8.5 microM for granisetron, ondansetron, dolasetron, and MDL 74,156, respectively. Block was relieved by strong hyperpolarizing potentials, suggesting a possible interaction with an inactivated channel state. Recovery from inactivation was impaired at -80 mV compared with -100 mV, and the fractional recovery was impaired by drug in a concentration-dependent manner. IC(50) values for block of the HERG cardiac K(+) channel measured 3.73, 0.81, 5.95, and 12.1 microM for granisetron, ondansetron, dolasetron, and MDL 74,156, respectively. Ondansetron (3 microM) also slowed decay of HERG tail currents. In contrast, none of these drugs (10 microM) produced greater than 30% block of the slow delayed rectifier K(+) channel KvLQT1/minK. We concluded that the antiemetic agents tested in this study block human cardiac Na(+) channels probably by interacting with the inactivated state. This may lead to clinically relevant Na(+) channel blockade, especially when high heart rates or depolarized/ischemic tissue is present. The submicromolar affinity of ondansetron for the HERG K(+) channel likely underlies the prolongation of cardiac repolarization reported for this drug.

Antiemetics↗
PubMed1996

Voltage-gated currents in identified parasympathetic cardiac neurons in the nucleus ambiguus.

Heart rate is normally dominated by the activity of the cardioinhibitory parasympathetic nervous system, while abnormally low levels of parasympathetic cardiac activity have been implicated in many cardiovascular diseases including hypertension, heart failure and sudden cardiac death. In this study we have examined the voltage-gated currents in parasympathetic cardiac neurons that were identified with a retrograde fluorescent tracer in visualized sections (250 microns) of nucleus ambiguus. Depolarization of parasympathetic cardiac neurons to potentials more positive than -50 mV evoked a rapidly activating and inactivating inward current which could be blocked by tetrodotoxin (TTX), although in some neurons up to 10 microM was required for complete block. The voltage-dependent inactivation properties of this Na current showed relatively broad inactivation characteristics, a characteristic of TTX-resistant Na channels. Depolarization also elicited biphasic outward currents, which were separated into a transient IA type K current using the specific channel antagonist 4-aminopyridine and a long-lasting delayed rectified K current. These voltage-gated Na and K currents define the action potential firing patterns of parasympathetic cardiac neurons, such as frequency adaptation and spike delay, and also determine the activity of these neurons in response to depolarizing and hyperpolarizing synaptic innervation.

4-Aminopyridine↗
PubMed1990

The acquisition during development of Ca-activated potassium currents by cochlear hair cells of the chick.

Voltage-clamp recordings were done on hair cells from a region of the chick's cochlea. In the adult, these cells have voltage-sensitive Ca currents and rapid, Ca-activated K currents that together support an electrical resonance, showing voltage oscillations at frequencies greater than 100 Hz. In embryos 14-days old (at one week before hatching) the same cells had a voltage-sensitive Ca current like that in adults, but a more slowly acting K current (of the delayed-rectifier type). In current-clamp they could generate only slowly repetitive action potentials. By two days before hatching, Ca-activated K currents were present. We suggest that the acquisition of Ca-activated K currents contributes to functional maturation of the chick's cochlea.

Action Potentials↗
PubMed1994

Evidence for two types of potassium current in rat choroid plexus epithelial cells.

The whole-cell patch-clamp technique was applied to rat choroid plexus epithelial cells. The resting membrane potential was -53 mV. The whole-cell conductance was mainly K+ selective, and the K+ current observed appeared to contain two distinct components. Depolarizing voltage pulses (more positive than 0 mV) evoked time-dependent outward currents which resembled delayed-rectifying K+ currents in other tissues. The current exhibited time-dependent activation and, at potentials more positive than 40 mV, slower time-dependent inactivation. The reversal potential measured by tail current analysis showed a shift of 43 mV for a tenfold increase in extracellular K+ concentration ([K+]o). The current was reduced by extracellular 5 mM Ba2+, 5 mM tetraethylammonium (TEA+), 5 mM Cs+ and 1 mM 4-aminopyridine (4-AP). In contrast, hyperpolarizing voltage pulses evoked time-independent, inward-rectifying currents. The reversal potential measured by voltage-ramp commands showed a shift of 42 mV for a tenfold increase in [K+]o. The chord conductance did not appear to increase with increasing [K+]o. The current was reduced by extracellular 5 mM Ba2+ and 0.5 mM Cs+, but not by 5 mM TEA+ or 1 mM 4-AP. These data suggest that two populations of K+ channel contribute to the conductance of choroid plexus epithelial cells.

Animals↗