Estrogen Transiently Increases Delayed Rectifier, Voltage-Dependent Potassium Currents in Ovine Gonadotropes

1999 ◽  
Vol 69 (4) ◽  
pp. 254-260 ◽  
Author(s):  
MichaelA. Cowley ◽  
Chen Chen ◽  
IainJ. Clarke
1992 ◽  
Vol 68 (4) ◽  
pp. 1143-1150 ◽  
Author(s):  
Y. Ueda ◽  
A. Kaneko ◽  
M. Kaneda

1. Horizontal cells of the cat retina were isolated by enzymatic dissociation. Two types of horizontal cells were identified: the axonless (A-type) horizontal cell having four to six thick, long (approximately 100 microns) dendrites, and the short-axon (B-type) horizontal cell having many (> 5) fine, short (approximately 30 microns) dendrites. 2. Membrane properties of isolated horizontal cells were analyzed under current-clamp and voltage-clamp conditions. In the A-type cell, the average resting potential was -55 mV and the mean membrane capacitance was 110 pF, whereas values in the B-type cell were -58 mV and 40 pF, respectively. The A-type cell showed long-lasting Ca spikes, but B-type cells had no Ca spikes. 3. Five types of voltage-dependent ionic currents were recorded: a sodium current (INa), a calcium current (ICa), and three types of potassium currents. Potassium currents consisted of potassium current through the inward rectifier (Ianomal), transient outward potassium current (IA), and potassium current through the delayed rectifier (IK(v)). INa was recorded only from A-type cells. Other currents were recorded from both types of cells. 4. INa activated when cells were depolarized from a holding potential (Vh) of -95 mV, and it was maximal at -25 mV. This current was blocked by tetrodotoxin. Approximately half of the A-type cells had INa, but no B-type cell had this current. 5. L-type ICa, an inward-going sustained current, was activated with depolarization more positive than -25 mV. Current amplitude reached a maximal value near 15 mV and became smaller with further depolarization.(ABSTRACT TRUNCATED AT 250 WORDS)


2000 ◽  
Vol 84 (6) ◽  
pp. 2888-2895 ◽  
Author(s):  
Haibin Wang ◽  
Gerry S. Oxford

Cell lines derived from tumors engineered in the CNS offer promise as models of specific neuronal cell types. CAD cells are an unusual subclone of a murine cell line derived from tyrosine hydroxylase (TH) driven tumorigenesis, which undergoes reversible morphological differentiation on serum deprivation. Using single-cell electrophysiology we have examined the properties of ion channels expressed in CAD cells. Despite relatively low resting potentials, CAD cells can be induced to fire robust action potentials when mildly artificially hyperpolarized. Correspondingly, voltage-dependent sodium and potassium currents were elicited under voltage clamp. Sodium currents are TTX sensitive and exhibit conventional activation and inactivation properties. The potassium currents reflected two pharmacologically distinguishable populations of delayed rectifier type channels while no transient A-type channels were observed. Using barium as a charge carrier, we observed an inactivating current that was completely blocked by nimodipine and thus associated with L-type calcium channels. On differentiation, three changes in functional channel expression occurred; a 4-fold decrease in sodium current density, a 1.5-fold increase in potassium current density, and the induction of a small noninactivating barium current component. The neuronal morphology, excitability properties, and changes in channel function with differentiation make CAD cells an attractive model for study of catecholaminergic neurons.


1996 ◽  
Vol 75 (1) ◽  
pp. 508-513 ◽  
Author(s):  
C. Griguer ◽  
P. A. Fuchs

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.


1997 ◽  
Vol 78 (5) ◽  
pp. 2649-2654 ◽  
Author(s):  
Michael Madeja ◽  
Ulrich Muβhoff ◽  
Norbert Binding ◽  
Ute Witting ◽  
Erwin-Josef Speckmann

Madeja, Michael, Ulrich Muβhoff, Norbert Binding, Ute Witting, and Erwin-Josef Speckmann. Effects of Pb2+ on delayed-rectifier potassium channels in acutely isolated hippocampal neurons. J. Neurophysiol. 78: 2649–2654, 1997. The effects of Pb2+ on delayed-rectifier potassium currents were studied in acutely isolated hippocampal neurons (CA1 neurons, CA3 neurons, granule cells) from the guinea pig using the patch-clamp technique in the whole cell configuration. Pb2+ in micromolar concentrations decreased the potassium currents in a voltage-dependent manner, which appeared as a shift of the current-voltage relation to positive potentials. The effect was reversible after washing. The concentration-responsiveness measured in CA1 neurons revealed an IC50 value of 30 μmol/l at a potential of −30 mV. The half-maximal shift of the current-voltage relation was reached at 33 μmol/l and the maximal obtainable shift was 13.4 mV. For the different types of hippocampal neurons, the shift of the current-voltage relation was distinct and was 7.9 mV in CA1 neurons, 13.7 mV in CA3 neurons, and 14.2 mV in granule cells with 50 μmol/l Pb2+. The effects described here of Pb2+ on the potassium currents in hippocampal neurons and the differences between the types of hippocampal neurons correspond with the known properties and distributions of cloned potassium channels found in the hippocampus. As a whole, our results demonstrate that Pb2+ in micromolar concentration is a voltage-dependent, reversible blocker of delayed-rectifier potassium currents of hippocampal neurons. This effect has to be taken into consideration as a possible contributing mechanism for the neurological symptoms of enhanced brain activity seen during Pb2+ intoxication.


Author(s):  
Leila Topal ◽  
Muhammad Naveed ◽  
Péter Orvos ◽  
Bence Pászti ◽  
János Prorok ◽  
...  

AbstractCannabis use is associated with known cardiovascular side effects such as cardiac arrhythmias or even sudden cardiac death. The mechanisms behind these adverse effects are unknown. The aim of the present work was to study the cellular cardiac electrophysiological effects of cannabidiol (CBD) on action potentials and several transmembrane potassium currents, such as the rapid (IKr) and slow (IKs) delayed rectifier, the transient outward (Ito) and inward rectifier (IK1) potassium currents in rabbit and dog cardiac preparations. CBD increased action potential duration (APD) significantly in both rabbit (from 211.7 ± 11.2. to 224.6 ± 11.4 ms, n = 8) and dog (from 215.2 ± 9.0 to 231.7 ± 4.7 ms, n = 6) ventricular papillary muscle at 5 µM concentration. CBD decreased IKr, IKs and Ito (only in dog) significantly with corresponding estimated EC50 values of 4.9, 3.1 and 5 µM, respectively, without changing IK1. Although the EC50 value of CBD was found to be higher than literary Cmax values after CBD smoking and oral intake, our results raise the possibility that potassium channel inhibition by lengthening cardiac repolarization might have a role in the possible proarrhythmic side effects of cannabinoids in situations where CBD metabolism and/or the repolarization reserve is impaired.


2012 ◽  
Vol 107 (5) ◽  
pp. 1356-1365 ◽  
Author(s):  
Subhashini Srinivasan ◽  
Kimberley Lance ◽  
Richard B. Levine

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.


2002 ◽  
Vol 87 (6) ◽  
pp. 2990-2995 ◽  
Author(s):  
Wolfgang Müller ◽  
Katrin Bittner

Oxidative stress is enhanced by [Ca2+]i-dependent stimulation of phospholipases and mitochondria and has been implicated in immune defense, ischemia, and excitotoxicity. Using whole cell recording from hippocampal neurons, we show that arachidonic acid (AA) and hydrogen peroxide (H2O2) both reduce the transient K+ current I A by −54 and −68%, respectively, and shift steady-state inactivation by −10 and −15 mV, respectively. While AA was effective at an extracellular concentration of 1 μM and an intracellular concentration of 1 pM, extracellular H2O2 was equally effective only at a concentration >800 μM (0.0027%). In contrast to AA, H2O2 decreased the slope of activation and increased the slope of inactivation of I A and reduced the sustained delayed rectifier current I K(V) by 22% and shifted its activation by −9 mV. Intracellular application of the antioxidant glutathione (GSH, 2–5 mM) blocked all effects of AA and the reduction of I A by H2O2. In contrast, intracellular GSH enhanced reduction of I K(V) by H2O2. Decrease of the slope of activation and increase of the slope of inactivation of I A by hydrogen peroxide was blocked and reversed to a decrease, respectively, by intracellular application of GSH. Intracellular GSH did not prevent H2O2 to shift inactivation and activation of I A and activation of I K(V) to more negative potentials. We conclude, that AA and H2O2modulate voltage-activated K currents differentially by oxidation of GSH accessible intracellular and GSH inaccessible extracellular K+-channel domains, thereby presumably affecting neuronal information processing and oxidative damage.


1994 ◽  
Vol 266 (3) ◽  
pp. C709-C719 ◽  
Author(s):  
S. M. Simasko

The role of Na+ in the expression of membrane potential activity in the clonal rat pituitary cell line GH3 was investigated using the perforated patch variation of patch-clamp electrophysiological techniques. It was found that replacing bath Na+ with choline, tris(hydroxymethyl)aminomethane (Tris), or N-methyl-D-glucamine (NMG) caused the cells to hyperpolarize 20-30 mV. Tetrodotoxin had no effect. The effects of the Na+ substitutes could not be explained by effects on potassium or calcium currents. Although all three Na+ substitutes suppressed voltage-dependent calcium current by 10-20%, block of voltage-dependent calcium current by nifedipine or Co2+ did not result in hyperpolarization of the cells. There was no effect of the Na+ substitutes on voltage-dependent potassium currents. In contrast, all three Na+ substitutes influenced calcium-activated potassium currents [IK(Ca)], but only at depolarized potentials. Choline consistently suppressed IK(Ca), whereas Tris and NMG either had no effect or slightly increased IK(Ca). These effects on IK(Ca) also cannot explain the hyperpolarization induced by removing bath Na+. Choline always hyperpolarized cells yet suppressed IK(Ca). Furthermore, removing bath Na+ caused an increase in cell input resistance, an observation consistent with the loss of a membrane conductance as the basis of the hyperpolarization. Direct measurement of background currents revealed a 12-pA inward current at -84 mV that was lost upon removing bath Na+. These results suggest that this background sodium conductance provides the depolarizing drive for GH3 cells to reach the threshold for firing calcium-dependent action potentials.


2008 ◽  
pp. 55-62
Author(s):  
HY Xu ◽  
X Huang ◽  
M Yang ◽  
J-B Sun ◽  
L-H Piao ◽  
...  

C-type natriuretic peptides (CNP) play an inhibitory role in smooth muscle motility of the gastrointestinal tract, but the effect of CNP on delayed rectifier potassium currents is still unclear. This study was designed to investigate the effect of CNP on delayed rectifier potassium currents and its mechanism by using conventional whole-cell patch-clamp technique in guinea-pig gastric myocytes isolated by collagenase. CNP significantly inhibited delayed rectifier potassium currents [I(K (V))] in dose-dependent manner, and CNP inhibited the peak current elicited by depolarized step pulse to 86.1+/-1.6 % (n=7, P<0.05), 78.4+/-2.6 % (n=10, P<0.01) and 67.7+/-2.3 % (n=14, P<0.01), at concentrations of 0.01 micromol/l, 0.1 micromol/l and 1 micromol/l, respectively, at +60 mV. When the cells were preincubated with 0.1 micromol/l LY83583, a guanylate cyclase inhibitor, the 1 ?micromol/l CNP-induced inhibition of I(K (V)) was significantly impaired but when the cells were preincubated with 0.1 micromol/l zaprinast, a cGMP-sensitive phosphodiesterase inhibitor, the 0.01 micromol/l CNP-induced inhibition of I(K (V)) was significantly potentiated. 8-Br-cGMP, a membrane permeable cGMP analogue mimicked inhibitory effect of CNP on I(K (V)). CNP-induced inhibition of I(K (V)) was completely blocked by KT5823, an inhibitor of cGMP-dependent protein kinase (PKG). The results suggest that CNP inhibits the delayed rectifier potassium currents via cGMP-PKG signal pathway in the gastric antral circular myocytes of the guinea-pig.


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