scholarly journals Chronic Ca2+influx through voltage-dependent Ca2+channels enhance delayed rectifier K+currents via activating Src family tyrosine kinase in rat hippocampal neurons

2017 ◽  
Vol 21 (2) ◽  
pp. 259 ◽  
Author(s):  
Yoon-Sil Yang ◽  
Sang-Chan Jeon ◽  
Dong-Kwan Kim ◽  
Su-Yong Eun ◽  
Sung-Cherl Jung
Keyword(s):  
Tyrosine Kinase ◽  
Hippocampal Neurons ◽  
Delayed Rectifier ◽  
Voltage Dependent ◽  
Ca2 Channels ◽  
K Currents

Differential Oxidative Modulation of Voltage-Dependent K+ Currents in Rat Hippocampal Neurons

2002 ◽  
Vol 87 (6) ◽  
pp. 2990-2995 ◽  
Author(s):  
Wolfgang Müller ◽  
Katrin Bittner
Keyword(s):  
Hydrogen Peroxide ◽  
Hippocampal Neurons ◽  
Immune Defense ◽  
Delayed Rectifier ◽  
Delayed Rectifier Current ◽  
Cell Recording ◽  
Voltage Dependent ◽  
Steady State Inactivation ◽  
K Currents ◽  
Stimulation Of

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.

scholarly journals Gonadotropin-Releasing Hormone Inhibits Ether-à-Go-Go-Related Gene K+ Currents in Mouse Gonadotropes

Endocrinology ◽  
2010 ◽  
Vol 151 (3) ◽  
pp. 1079-1088 ◽  
Author(s):  
Wiebke Hirdes ◽  
Crenguta Dinu ◽  
Christiane K. Bauer ◽  
Ulrich Boehm ◽  
Jürgen R. Schwarz
Keyword(s):  
Resting Potential ◽  
Related Gene ◽  
Activation Curve ◽  
Signal Cascade ◽  
Primary Mouse ◽  
Voltage Dependent ◽  
K Current ◽  
Unknown Signal ◽  
Ca2 Channels ◽  
K Currents

Secretion of LH from gonadotropes is initiated by a GnRH-induced increase in intracellular Ca2+ concentration ([Ca2+]i). This increase in [Ca2+]i is the result of Ca2+ release from intracellular stores and Ca2+ influx through voltage-dependent Ca2+ channels. Here we describe an ether-à-go-go-related gene (erg) K+ current in primary mouse gonadotropes and its possible function in the control of Ca2+ influx. To detect gonadotropes, we used a knock-in mouse strain, in which GnRH receptor-expressing cells are fluorescently labeled. Erg K+ currents were recorded in 80–90% of gonadotropes. Blockage of erg currents by E-4031 depolarized the resting potential by 5–8 mV and led to an increase in [Ca2+]i, which was abolished by nifedipine. GnRH inhibited erg currents by a reduction of the maximal erg current and in some cells additionally by a shift of the activation curve to more positive potentials. In conclusion, the erg current contributes to the maintenance of the resting potential in gonadotropes, thereby securing a low [Ca2+]i by restricting Ca2+ influx. In addition, the erg channels are modulated by GnRH by an as-yet unknown signal cascade.

Somatostatin increases voltage-dependent potassium currents in rat somatotrophs

1990 ◽  
Vol 259 (6) ◽  
pp. C854-C861 ◽  
Author(s):  
C. Chen ◽  
J. Zhang ◽  
J. D. Vincent ◽  
J. M. Israel
Keyword(s):  
Growth Hormone ◽  
Cell Voltage ◽  
Inhibitory Effect ◽  
Delayed Rectifier ◽  
Hormone Release ◽  
Growth Hormone Release ◽  
Voltage Dependent ◽  
Inward Currents ◽  
K Current ◽  
K Currents

To study the modulatory effects of somatostatin on membrane K+ currents, whole cell voltage-clamp recordings were performed on identified rat somatotrophs in primary culture. In the presence of Co2+ (2 mM) and tetrodotoxin (1 microM) in the bath solution to block Ca2+ and Na+ inward currents, two types of voltage-activated K+ currents were identified on the basis of their kinetics and pharmacology. First, a delayed rectifier K+ current (IK) had a threshold of -20 mV, did not decay during voltage steps lasting 300 ms, and was markedly attenuated by extracellular application of tetraethylammonium (TEA, 10 mM). Second, a transient outward K+ current (IA) was activated at -40 mV (from a holding potential of -80 mV) and persisted despite the presence of TEA. This IA was blocked by 4-aminopyridine (2 mM). Somatostatin (10 nM) increased IK by 75% and IA by 45% without obvious effects on steady-state voltage dependency of activation or inactivation, and these effects were reversible. This increase in K+ currents may contribute in part to the inhibitory effect of somatostatin on growth hormone release.

Membrane currents in a calcitonin-secreting human C cell line

1992 ◽  
Vol 263 (5) ◽  
pp. C986-C994 ◽  
Author(s):  
B. A. Biagi ◽  
B. Mlinar ◽  
J. J. Enyeart
Keyword(s):  
Cell Line ◽  
Time Constant ◽  
Membrane Currents ◽  
Human Thyroid ◽  
Delayed Rectifier ◽  
Patch Clamp Technique ◽  
Voltage Gated ◽  
Voltage Dependent ◽  
Tt Cells ◽  
K Currents

The whole cell version of the patch-clamp technique was used to identify and characterize voltage-gated Ca2+, Na+, and K+ currents in the calcitonin-secreting human thyroid TT cell line. Ca2+ current consisted of a single low-voltage-activated rapidly inactivating component. The current was one-half maximally activated at a potential of -27 mV, while steady-state voltage-dependent inactivation was one-half complete at -51 mV. The Ca2+ current inactivated with a voltage-dependent time constant that reached a minimum of 16 ms at potentials positive to -15 mV. Deactivation kinetics could also be fit with a single voltage-dependent time constant of approximately 2 ms at -80 mV. Replacing Ca2+ with Ba2+ reduced the maximum current by 18 +/- 5% (n = 6). The dihydropyridine Ca2+ agonist (-)BAY K 8644 did not affect the Ca2+ current, but 50 microM Ni2+ reduced it by 81 +/- 0.8% (n = 5). TT cells also possessed tetrodotoxin-sensitive voltage-gated Na+ channels and tetraethylammonium-sensitive delayed rectifier type K+ currents. These results indicate that TT cells possess membrane currents necessary for the generation of action potentials. T-type Ca2+ channels are the sole pathway for voltage-dependent Ca2+ entry into these cells and may couple electrical activity to calcitonin secretion.

Potassium currents in the inner segment of single retinal cone photoreceptors

1990 ◽  
Vol 64 (6) ◽  
pp. 1929-1940 ◽  
Author(s):  
A. V. Maricq ◽  
J. I. Korenbrot
Keyword(s):  
Voltage Dependence ◽  
Delayed Rectifier ◽  
Half Maximum ◽  
Cone Photoreceptors ◽  
Delayed Rectifier Current ◽  
Maximum Activation ◽  
Voltage Dependent ◽  
Kinetics Of ◽  
K Currents ◽  
Steepness Factor

1. The K+ currents of cone inner segments isolated from the retina of a lizard were studied with the use of tight-seal electrodes in the whole cell configuration. To conduct these studies other identified currents in the cell were blocked. Co2+ blocked a voltage-dependent Ca2+ current and a Ca2(+)-dependent Cl- current, and Cs+ blocked an inward-rectifying current partially carried by K+. 2. The cells sustained a voltage-dependent K+ current that was blocked by tetraethylammonium (TEA)+ and had characteristics typical of the delayed rectifier. However, we found no evidence for the existence of “A”-type K+ currents or Ca2(+)-dependent K+ currents. 3. The delayed-rectifier current was nearly ideally selective for K+. Increasing external K+ concentration 10-fold shifted the reversal potential by 55 mV. 4. Analysis of the voltage dependence of the activation of the delayed-rectifier current revealed the existence of two distinct subclasses of this current. We referred to them as IdrL and IdrH for low and high threshold of voltage activation. 5. IdrL activated at voltages above -70 mV. Its dependence on voltage was described by Boltzmann's function with average half-maximum activation at -51 mV and steepness factor k = 7.5 mV. IdrH activated at voltages above -50 mV. Its dependence on voltage was described by Boltzmann's function with average half-maximum activation at -4.6 mV and steepness factor k = 17.1 mV. 6. Of nine cells analyzed in detail, one demonstrated IdrH alone, whereas the remaining had a variable mixture of the two current subtypes. At maximum activation the current through IdrL ranged between 0.3 and 0.5 of the total delayed-rectifier current. 7. The kinetics of activation of the total delayed-rectifier current were described by the sum of two exponentials the amplitudes and time constants of which were voltage dependent. However, the kinetics of the current subtypes were not resolved individually. The current inactivated slowly with a single-exponential time course that was voltage dependent. 8. The voltage dependence of the delayed-rectifier current indicates the current is active in a cone photoreceptor in the dark. The current is 20-30 pA in amplitude at the dark-membrane potential and outwardly directed. 9. IdrL may generate a rapid relaxation of photovoltages activated by dim lights--those that hyperpolarize the membrane by only a few millivolts. The delayed-rectifier currents help shape the action potentials that can be generated in isolated cone photoreceptors

Choline chloride activates time-dependent and time-independent K+ currents in dog atrial myocytes

1994 ◽  
Vol 266 (1) ◽  
pp. C42-C51 ◽  
Author(s):  
B. Fermini ◽  
S. Nattel
Keyword(s):  
Choline Chloride ◽  
Outward Current ◽  
Time Dependent ◽  
Equilibrium Potential ◽  
Delayed Rectifier ◽  
Atrial Myocytes ◽  
Patch Clamp Technique ◽  
Voltage Dependent ◽  
K Current ◽  
K Currents

Using the whole cell configuration of the patch-clamp technique, we studied the effect of isotonic replacement of bath sodium chloride (NaCl) by choline chloride (ChCl) in dog atrial myocytes. Our results show that ChCl triggered 1) activation of a time-independent background current, characterized by a shift of the holding current in the outward direction at potentials positive to the K+ equilibrium potential (EK), and 2) activation of a time- and voltage-dependent outward current, following depolarizing voltage steps positive to EK. Because the choline-induced current obtained by depolarizing steps exhibited properties similar to the delayed rectifier K+ current (IK), we named it IKCh. The amplitude of IKCh was determined by extracellular ChCl concentration, and this current was generally undetectable in the absence of ChCl. IKCh was not activated by acetylcholine (0.001-1.0 mM) or carbachol (10 microM) and could not be recorded in the absence of ChCl or when external NaCl was replaced by sucrose or tetramethylammonium chloride. IKCh was inhibited by atropine (0.01-1.0 microM) but not by the M1 antagonist pirenzepine (up to 10 microM). This current was carried mainly by K+ and was inhibited by CsCl (120 mM, in the pipette) or barium (1 mM, in the bath). We conclude that in dog atrial myocytes, ChCl activates a background conductance comparable to ACh-dependent K+ current, together with a time-dependent K+ current showing properties similar to IK.

Voltage-activated potassium currents of rabbit osteoclasts: effects of extracellular calcium

1994 ◽  
Vol 267 (4) ◽  
pp. C1103-C1111 ◽  
Author(s):  
L. G. Hammerland ◽  
A. S. Parihar ◽  
E. F. Nemeth ◽  
M. C. Sanguinetti
Keyword(s):  
Negative Charge ◽  
Voltage Dependence ◽  
Physiological Function ◽  
Inward Rectifier ◽  
Delayed Rectifier ◽  
Voltage Dependent ◽  
K Current ◽  
Kinetics Of ◽  
K Currents ◽  
Simple Surface

The effects of increased extracellular Ca2+ concentration ([Ca2+]e) were examined on a delayed-rectifier K+ current (IK) and an inward-rectifier K+ current (IK1) in rabbit osteoclasts. Elevation of [Ca2+]e from 1.8 to 18 mM shifted the half point for IK activation by +11.5 mV and the voltage dependence of inactivation by +9.7 mV and slowed the rate of IK activation and deactivation. These effects of elevated [Ca2+]e on IK are consistent with screening of cell surface negative charge. However, elevation of [Ca2+]e increased the voltage-dependent kinetics of IK inactivation at all potentials tested, inconsistent with that predicted by simple surface charge theory. This finding suggests an additional, regulatory role for [Ca2+]e in the gating of IK channels. Some osteoclasts had an IK1, which was decreased when [Ca2+]e was raised from 1.8 to 18 mM. The physiological function of both types of K+ currents remains to be determined, and it is not clear whether these currents are involved with the coupling of cytosolic [Ca2+] to [Ca2+]e.

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

1988 ◽  
Vol 91 (2) ◽  
pp. 255-274 ◽  
Author(s):  
C Marchetti ◽  
R T Premont ◽  
A M Brown
Keyword(s):  
Single Channel ◽  
Reversal Potential ◽  
Outward Current ◽  
Single Type ◽  
K Channel ◽  
Delayed Rectifier ◽  
Patch Clamp Technique ◽  
Voltage Dependent ◽  
Single Channel Currents ◽  
K Currents

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.

Glibenclamide depresses the slowly inactivating outward current (ID) in hippocampal neurons

1992 ◽  
Vol 70 (2) ◽  
pp. 306-307 ◽  
Author(s):  
Valérie Crépel ◽  
Kresimir Krnjević ◽  
Yehezkel Ben-Ari
Keyword(s):  
Adenosine Triphosphate ◽  
Hippocampal Neurons ◽  
Wistar Rats ◽  
Hippocampal Slices ◽  
Outward Current ◽  
K Channels ◽  
Voltage Dependent ◽  
Ca3 Neurons ◽  
K Currents

Sulphonylurea drugs, such as glibenclamide and tolbutamide, are widely used as selective blockers of adenosine triphosphate-sensitive K channels. In experiments on hippocampal slices (from Wistar rats) glibenclamide (and possibly gliquidone and tolbutamide) significantly reduced the highly voltage-dependent, 4-aminopyridine-sensitive D-type outward current of CA3 neurons. Judging by these observations, the sulphonylureas may not be as selective as generally believed.Key words: glibenclamide, gliquidone, tolbutamide, K currents, rat hippocampal slices.

Differential modulation of voltage-dependent K+ currents in colonic smooth muscle by oxidants

2004 ◽  
Vol 286 (3) ◽  
pp. C671-C682 ◽  
Author(s):  
Madhu Prasad ◽  
Raj K. Goyal
Keyword(s):  
Smooth Muscle ◽  
Delayed Rectifier ◽  
Channel Blockers ◽  
Methionine Oxidation ◽  
Differential Modulation ◽  
Nitrobenzoic Acid ◽  
Voltage Dependent ◽  
Chloramine T ◽  
Methionine Residues ◽  
K Currents

The effect of oxidants on voltage-dependent K+ currents was examined in mouse colonic smooth muscle cells. Exposure to either chloramine-T (Ch-T), an agent known to oxidize both cysteine and methionine residues, or the colon-specific oxidant monochloramine (NH2Cl) completely suppressed the transient outward K+ current ( Ito) while simultaneously enhancing the sustained delayed rectifier K+ current ( Idr). In contrast, the cysteine-specific oxidants hydrogen peroxide (H2O2) and 5,5′-dithiobis(2-nitrobenzoic acid) (DTNB) exhibited partial and slow suppression of Ito by inducing a shift in channel availability of -18 mV without affecting Idr. After enhancement by NH2Cl or Ch-T, Idr was sensitive to 10 mM tetraethylammonium but not to other K+ channel blockers, suggesting that it represented activation of the resting Idr and not a separate K+ conductance. Extracellular dithiothreitol (DTT) partially reversed the effect of H2O2 and DTNB on Ito but not the actions of NH2Cl and Ch-T on either Idr or Ito. Dialysis of myocytes with GSH (5 mM) or DTT (5 mM) prevented suppression of Ito by H2O2 and DTNB but did not alter the effects of NH2Cl or Ch-T on either Idr or Ito. Ch-T and NH2Cl completely blocked Ito generated by murine Kv4.1, 4.2, and 4.3 in Xenopus oocytes, an effect not reversible by intracellular DTT. In contrast, intracellular DTT reversed the effect of H2O2 and DTNB on the cloned channels. These results suggest that Ito is suppressed via modification of both methionine and cysteine residues, whereas enhancement of Idr likely results from methionine oxidation alone.

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