scholarly journals KCR1, a Membrane Protein That Facilitates Functional Expression of Non-inactivating K+Currents Associates with Rat EAG Voltage-dependent K+Channels

1998 ◽  
Vol 273 (36) ◽  
pp. 23080-23085 ◽  
Author(s):  
Naoto Hoshi ◽  
Hiroto Takahashi ◽  
Mohammad Shahidullah ◽  
Shigeru Yokoyama ◽  
Haruhiro Higashida
Keyword(s):  
Membrane Protein ◽  
Functional Expression ◽  
K Channels ◽  
Voltage Dependent ◽  
K Currents

Structural Correlates of K+ Channel Function

Physiology ◽  
1994 ◽  
Vol 9 (4) ◽  
pp. 169-173 ◽  
Author(s):  
M Taglialatela ◽  
AM Brown
Keyword(s):  
Ion Channel ◽  
Ionic Currents ◽  
The Other ◽  
K Channel ◽  
K Channels ◽  
Functional Studies ◽  
Channel Function ◽  
Voltage Dependent ◽  
K Currents

More complementary DNAs have been cloned for Voltage-dependent K+ channels than any other voltage-dependent ion channel. Purely functional studies anticipated this result because K+ currents are far more diverse than voltage-dependent Na+, Ca2+, or Cl currents, the other types of voltage-dependent ionic currents commonly dealt with.

scholarly journals HERG-like K+ Channels in Microglia

1998 ◽  
Vol 111 (6) ◽  
pp. 781-794 ◽  
Author(s):  
Wei Zhou ◽  
Francisco S. Cayabyab ◽  
Peter S. Pennefather ◽  
Lyanne C. Schlichter ◽  
Thomas E. DeCoursey
Keyword(s):  
Primary Cultures ◽  
Cell Voltage ◽  
Companion Paper ◽  
Inward Rectifier ◽  
K Channels ◽  
Voltage Dependent ◽  
Slope Factor ◽  
A Cell ◽  
Selective Blocker ◽  
K Currents

A voltage-gated K+ conductance resembling that of the human ether-à-go-go-related gene product (HERG) was studied using whole-cell voltage-clamp recording, and found to be the predominant conductance at hyperpolarized potentials in a cell line (MLS-9) derived from primary cultures of rat microglia. Its behavior differed markedly from the classical inward rectifier K+ currents described previously in microglia, but closely resembled HERG currents in cardiac muscle and neuronal tissue. The HERG-like channels opened rapidly on hyperpolarization from 0 mV, and then decayed slowly into an absorbing closed state. The peak K+ conductance–voltage relation was half maximal at −59 mV with a slope factor of 18.6 mV. Availability, assessed by a hyperpolarizing test pulse from different holding potentials, was more steeply voltage dependent, and the midpoint was more positive (−14 vs. −39 mV) when determined by making the holding potential progressively more positive than more negative. The origin of this hysteresis is explored in a companion paper (Pennefather, P.S., W. Zhou, and T.E. DeCoursey. 1998. J. Gen. Physiol. 111:795–805). The pharmacological profile of the current differed from classical inward rectifier but closely resembled HERG. Block by Cs+ or Ba2+ occurred only at millimolar concentrations, La3+ blocked with Ki = ∼40 μM, and the HERG-selective blocker, E-4031, blocked with Ki = 37 nM. Implications of the presence of HERG-like K+ channels for the ontogeny of microglia are discussed.

Aminopyridine inhibition and voltage dependence of K+ currents in smooth muscle cells from cerebral arteries

1994 ◽  
Vol 267 (6) ◽  
pp. C1589-C1597 ◽  
Author(s):  
B. E. Robertson ◽  
M. T. Nelson
Keyword(s):  
Smooth Muscle ◽  
Steady State ◽  
Smooth Muscle Cells ◽  
Voltage Dependence ◽  
Muscle Cells ◽  
Membrane Depolarization ◽  
K Channels ◽  
Voltage Dependent ◽  
Basilar Arteries ◽  
K Currents

Voltage-dependent K+ currents were characterized using the patch-clamp technique in smooth muscle cells isolated from rabbit cerebral (basilar) arteries. This study focused on the voltage dependence and the pharmacology of these K+ currents, since this information will be useful for the investigation of the role of the voltage-dependent K+ channels in arterial function. Currents through Ca(2+)-activated K+ (KCa) channels were minimized by buffering intracellular Ca2+ to low levels and by blockers (tetraethylammonium and iberiotoxin) of these channels. Membrane depolarization increased K+ currents, independent of changes in the driving force for K+ movement. With 140 mM internal and external K+, activation of K+ currents by membrane depolarization was half maximal at about -10 mV and increased as much as e-fold per 11 mV. Inactivation also depended on voltage, with a midpoint at -44 mV. 3,4-Diaminopyridine (3,4-DAP),4-aminopyridine(4-AP),3-amino-pyridine(3-AP), and 2-aminopyridine (2-AP) inhibited voltage-dependent K+ currents. At 0 mV, 3,4-DAP, 4-AP, 3-AP, and 2-AP (5 mM) inhibited the K+ currents by 84, 66, 36, and 8%, respectively. Phencyclidine (100 microM) inhibited the current by 53% at 0 mV. Steady-state whole cell currents through these channels were measured at physiological membrane potentials. At -40 mV, 4-AP (5 mM) reduced the steady-state outward current by 2.5 pA. These results are consistent with the idea that voltage-dependent K+ channels are involved in the regulation of the membrane potential of arterial smooth muscle.

Differential Effects of Lidocaine and Mexiletine on Relaxations to ATP-sensitive K+Channel Openers in Rat Aortas 

1999 ◽  
Vol 90 (4) ◽  
pp. 1165-1170 ◽  
Author(s):  
Hiroyuki Kinoshita ◽  
Toshizo Ishikawa ◽  
Yoshio Hatano
Keyword(s):  
Smooth Muscle ◽  
Antiarrhythmic Drugs ◽  
Isometric Force ◽  
K Channel ◽  
Response Curves ◽  
K Channels ◽  
Voltage Dependent ◽  
K Currents ◽  
Class Ib ◽  
Isolated Rat

Background In cardiac myocytes, lidocaine reduces but mexiletine increases adenosine triphosphate (ATP)-sensitive K+ currents, suggesting that these class Ib antiarrhythmic drugs may differentially modify the activity of ATP-sensitive K+ channels. The effects of lidocaine and mexiletine on arterial relaxations induced by K+ channel openers have not been studied. Therefore, the current study was designed to evaluate whether lidocaine and mexiletine may produce changes in relaxations to the ATP-sensitive K+ channel openers cromakalim and pinacidil in isolated rat thoracic aortas. Methods Rings of rat thoracic aortas without endothelia were suspended for isometric force recording. Concentration-response curves were obtained in a cumulative fashion. During submaximal contractions to phenylephrine (3 x 10(-7) M), relaxations to cromakalim (10(-7) to 3 x 10(-5) M), pinacidil (10(-7) to 3 x 10(-5) M), or diltiazem (10(-7) to 3 x 10(-4) M) were obtained. Lidocaine (10(-5) to 3 x 10(-4) M), mexiletine (10(-5) to 10(-4) M) or glibenclamide (5 x 10(-6) M) was applied 15 min before addition of phenylephrine. Results During contractions to phenylephrine, cromakalim and pinacidil induced concentration-dependent relaxations. A selective ATP-sensitive K+ channel antagonist, glibenclamide (5 x 10(-6) M), abolished these relaxations, whereas it did not alter relaxations to a voltage-dependent Ca2+ channel inhibitor, diltiazem (10(-7) to 3 x 10(-4) M). Lidocaine (more than 10(-5) M) significantly reduced relaxations to cromakalim or pinacidil in a concentration-dependent fashion, whereas lidocaine (3 x 10(-4) M) did not affect relaxations to diltiazem. In contrast, mexiletine (more than 10(-5) M) significantly augmented relaxations to cromakalim or pinacidil. Glibenclamide (5 x 10(-6) M) abolished relaxations to cromakalim or pinacidil in arteries treated with mexiletine (10(-4) M). Conclusions These results suggest that lidocaine impairs but mexiletine augments vasodilation mediated by ATP-sensitive K+ channels in smooth muscle cells.

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.

scholarly journals Transmitter regulation of voltage-dependent K+ channels expressed in Xenopus oocytes

1991 ◽  
Vol 277 (3) ◽  
pp. 899-902 ◽  
Author(s):  
M P Kavanaugh ◽  
M J Christie ◽  
P B Osborne ◽  
A E Busch ◽  
K Z Shen ◽  
...  
Keyword(s):  
Xenopus Oocytes ◽  
K Channels ◽  
Intracellular Injection ◽  
Inner Surface ◽  
Voltage Dependent ◽  
K Current ◽  
S Application ◽  
K Currents

Voltage-dependent K+ channels (RBK1, RBK2 and RGK5) were co-expressed in Xenopus oocytes with 5-hydroxytryptamine (5-HT2) receptors. K+ currents measured 2-4 days later were inhibited by 5-HT (100 nM-10 microM, 20-30 s application) by up to 90%. The effect of 5-HT was mimicked by intracellular injection of Ins(1,4,5)P3. Increasing the Ca2+ concentration at the inner surface of excised membrane patches did not decrease the K+ current.

scholarly journals Voltage-dependent K+ currents and underlying single K+ channels in pheochromocytoma cells.

1988 ◽  
Vol 91 (1) ◽  
pp. 73-106 ◽  
Author(s):  
T Hoshi ◽  
R W Aldrich
Keyword(s):  
Time Course ◽  
Single Channel ◽  
Patch Clamp Recording ◽  
External Application ◽  
Pharmacological Agents ◽  
Whole Cell ◽  
K Channels ◽  
Pc 12 Cells ◽  
Voltage Dependent ◽  
K Currents

Properties of the whole-cell K+ currents and voltage-dependent activation and inactivation properties of single K+ channels in clonal pheochromocytoma (PC-12) cells were studied using the patch-clamp recording technique. Depolarizing pulses elicited slowly inactivating whole-cell K+ currents, which were blocked by external application of tetraethylammonium+, 4-aminopyridine, and quinidine. The amplitudes and time courses of these K+ currents were largely independent of the prepulse voltage. Although pharmacological agents and manipulation of the voltage-clamp pulse protocol failed to reveal any additional separable whole-cell currents in a majority of the cells examined, single-channel recordings showed that, in addition to the large Ca++-dependent K+ channels described previously in many other preparations, PC-12 cells had at least four distinct types of K+ channels activated by depolarization. These four types of K+ channels differed in the open-channel current-voltage relation, time course of activation and inactivation, and voltage dependence of activation and inactivation. These K+ channels were designated the Kw, Kz, Ky, and Kx channels. The typical chord conductances of these channels were 18, 12, 7, and 7 pS in the excised configuration using Na+-free saline solutions. These four types of K+ channels opened in the presence of low concentrations of internal Ca++ (1 nM). Their voltage-dependent gating properties can account for the properties of the whole-cell K+ currents in PC-12 cells.

scholarly journals Activation and Two Modes of Blockade by Strontium of Ca2+-activated K+ Channels in Goldfish Saccular Hair Cells

1998 ◽  
Vol 111 (2) ◽  
pp. 363-379 ◽  
Author(s):  
Izumi Sugihara
Keyword(s):  
Dissociation Constant ◽  
Time Constant ◽  
Hair Cells ◽  
Single Channel ◽  
Hill Coefficient ◽  
K Channels ◽  
Voltage Dependent ◽  
Time Courses ◽  
The Hill ◽  
Inside Out

Effects of internal Sr2+ on the activity of large-conductance Ca2+-activated K+ channels were studied in inside-out membrane patches from goldfish saccular hair cells. Sr2+ was approximately one-fourth as potent as Ca2+ in activating these channels. Although the Hill coefficient for Sr2+ was smaller than that for Ca2+, maximum open-state probability, voltage dependence, steady state gating kinetics, and time courses of activation and deactivation of the channel were very similar under the presence of equipotent concentrations of Ca2+ and Sr2+. This suggests that voltage-dependent activation is partially independent of the ligand. Internal Sr2+ at higher concentrations (>100 μM) produced fast and slow blockade both concentration and voltage dependently. The reduction in single-channel amplitude (fast blockade) could be fitted with a modified Woodhull equation that incorporated the Hill coefficient. The dissociation constant at 0 mV, the Hill coefficient, and zd (a product of the charge of the blocking ion and the fraction of the voltage difference at the binding site from the inside) in this equation were 58–209 mM, 0.69–0.75, 0.45–0.51, respectively (n = 4). Long shut events (slow blockade) produced by Sr2+ lasted ∼10–200 ms and could be fitted with single-exponential curves (time constant, τl−s) in shut-time histograms. Durations of burst events, periods intercalated by long shut events, could also be fitted with single exponentials (time constant, τb). A significant decrease in τb and no large changes in τl−s were observed with increased Sr2+ concentration and voltage. These findings on slow blockade could be approximated by a model in which single Sr2+ ions bind to a blocking site within the channel pore beyond the energy barrier from the inside, as proposed for Ba2+ blockade. The dissociation constant at 0 mV and zd in the Woodhull equation for this model were 36–150 mM and 1–1.8, respectively (n = 3).

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