Roles of the voltage-gated K + channel subunits, Kv 1.5 and Kv 1.4, in the developmental changes of K + currents in cultured neonatal rat ventricular cells

1997 ◽  
Vol 434 (2) ◽  
pp. 206-208 ◽  
Author(s):  
W. Guo ◽  
K. Kamiya ◽  
J. Toyama
Keyword(s):  
Developmental Changes ◽  
Neonatal Rat ◽  
K Channel ◽  
Voltage Gated ◽  
Ventricular Cells ◽  
K Currents

scholarly journals MiR-223-3p as a Novel MicroRNA Regulator of Expression of Voltage-Gated K+ Channel Kv4.2 in Acute Myocardial Infarction

2016 ◽  
Vol 39 (1) ◽  
pp. 102-114 ◽  
Author(s):  
Xue Liu ◽  
Ying Zhang ◽  
Weijie Du ◽  
Haihai Liang ◽  
Hua He ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Protein Level ◽  
Neonatal Rat ◽  
Luciferase Assay ◽  
K Channel ◽  
Voltage Gated ◽  
Ventricular Cells ◽  
Repressive Effect ◽  
Ischemic Arrhythmias

Background/Aims: Acute myocardial infarction (AMI) is a devastating cardiovascular disease with a high rate of morbidity and mortality, partly due to enhanced arrhythmogenicity. MicroRNAs (miRNAs) have been shown to participate in the regulation of cardiac ion channels and the associated arrhythmias. The purpose of this study was to test our hypothesis that miR-223-3p contributes to the electrical disorders in AMI via modulating KCND2, the gene encoding voltage-gated channel Kv4.2 that carries transient outward K+ current Ito. Methods: AMI model was established in male Sprague-Dawley (SD) rats by left anterior descending artery (LAD) ligation. Evans blue and TTC staining was used to measure infarct area. Ito was recorded in isolated ventricular cardiomyocytes or cultured neonatal rat ventricular cells (NRVCs) by whole-cell patch-clamp techniques. Western blot analysis was employed to detect the protein level of Kv4.2 and real-time RT-PCR to determine the transcript level of miR-223-3p. Luciferase assay was used to examine the interaction between miR-223-3p and KCND2 in cultured NRVCs. Results: Expression of miR-223-3p was remarkably upregulated in AMI relative to sham control rats. On the contrary, the protein level of Kv4.2 and Ito density were significantly decreased in AMI. Consistently, transfection of miR-223-3p mimic markedly reduced Kv4.2 protein level and Ito current in cultured NRVCs. Co-transfection of AMO-223-3p (an antisense inhibitor of miR-223-3p) reversed the repressive effect of miR-223-3p. Luciferase assay showed that miR-223-3p, but not the negative control, substantially suppressed the luciferase activity, confirming the direct binding of miR-223-3p to the seed site within the KCND2 sequence. Finally, direct intramuscular injection of AMO-223-3p into the ischemic myocardium to knockdown endogenous miR-223-3p decreased the propensity of ischemic arrhythmias. Conclusions: Upregulation of miR-223-3p in AMI repressed the expression of KCND2/Kv4.2 resulting in reduction of Ito density that can cause APD prolongation and promote arrhythmias in AMI, and therefore knockdown of endogenous miR-223-3p might be considered a new approach for antiarrhythmic therapy of ischemic arrhythmias.

Potassium channel block does not affect metabolic responses of brown fat cells

1992 ◽  
Vol 262 (3) ◽  
pp. C678-C681 ◽  
Author(s):  
P. A. Pappone ◽  
M. T. Lucero
Keyword(s):  
Potassium Channels ◽  
Metabolic Response ◽  
Brown Fat ◽  
Neonatal Rat ◽  
K Channel ◽  
Fat Cells ◽  
Adrenergic Stimulation ◽  
K Channels ◽  
Voltage Gated ◽  
Calcium Activated Potassium Channels

Hormonally stimulated brown fat cells are capable of extremely high metabolic rates, making them an excellent system in which to examine the role of plasma membrane ion channels in cell metabolism. We have previously shown that brown fat cell membranes have both voltage-gated and calcium-activated potassium channels (Voltage-gated potassium channels in brown fat cells. J. Gen. Physiol. 93: 451-472, 1989; Membrane responses to norepinephrine in cultured brown fat cells. J. Gen. Physiol. 95: 523-544, 1990). Currents through both the voltage-activated potassium channels, IK,V, and the calcium-activated potassium channels, IK,Ca, can be blocked by the membrane-impermeant K channel blocker tetraethylammonium (TEA). We used microcalorimetric measurements from isolated neonatal rat brown fat cells to assess the role these potassium conductances play in the metabolic response of brown fat cells to adrenergic stimulation. Concentrations of TEA as high as 50 mM, sufficient to block approximately 95% of IK,V and 100% of IK,Ca, had no effect on norepinephrine-stimulated heat production. These results show that neither voltage-gated nor calcium-activated K channels are necessary for a maximal thermogenic response in brown fat cells and suggest that K channels are not involved in maintaining cellular homeostasis during periods of high metabolic activity.

Differential Effects of Etomidate, Propofol, and Midazolam on Calcium and Potassium Channel Currents in Canine Myocardial Cells

1996 ◽  
Vol 85 (5) ◽  
pp. 1092-1099 ◽  
Author(s):  
Nediljka Buljubasic ◽  
Jure Marijic ◽  
Viktor Berczi ◽  
Darko F. Supan ◽  
John P. Kampine ◽  
...  
Keyword(s):  
Cell Voltage ◽  
K Channel ◽  
Inotropic Effects ◽  
Intravenous Anesthetics ◽  
Ventricular Cells ◽  
Dependent Inactivation ◽  
Dependent Inhibition ◽  
Channel Currents ◽  
Final Effect ◽  
K Currents

Background Intravenous anesthetics etomidate, propofol, and midazolam produce negative inotropic effects of various degrees. The mechanism underlying these differences is largely unknown. Methods The effects of intravenous anesthetics on L-type Ca2+, transient outward and inward-rectifier K+ channel currents (ICa, IKto, and IK1) were compared in canine ventricular cells using the whole-cell voltage-clamp technique. ICa and IK were elicited by progressively depolarizing cells from -40 to +40 mV, and from -90 to +60 mV, respectively. The peak amplitude and time-dependent inactivation rate of ICa and IK were measured before, during, and after the administration of equimolar concentrations (5, 30, or 60 microM) of etomidate, propofol, or midazolam. Results Exposure to etomidate, propofol, and midazolam produced a concentration-dependent inhibition of ICa. Midazolam was the most potent intravenous anesthetic; at 60 microM, etomidate, propofol, and midazolam decreased peak ICa by 16 +/- 4% (mean +/- SEM), 33 +/- 5%, and 47 +/- 5%, respectively. Etomidate, propofol, and midazolam given in a 60-microM concentration decreased IKto by 8 +/- 3%, 9 +/- 2%, and 23 +/- 3%, respectively. IK1 was decreased by 60 microM etomidate and midazolam by 20 +/- 6% and 14% +/- 5%, respectively. Propofol had no effect on IK1. Conclusions At equimolar concentrations, intravenous anesthetics decreased the peak ICa, IKto, and IK1 with various degrees of potency. Effects of anesthetics on ICa were significantly greater compared with their effects on K+ currents. These findings suggest that the negative inotropic actions of etomidate, propofol, and midazolam are related, at least in part, to decreased ICa. Some effects, such as IK inhibition, may partially antagonize effects of decreased ICa. Indeed, the final effect of these intravenous anesthetics on myocardium will be the sum of these and other sarcolemmal and intracellular effects.

Voltage-gated K+-channel activity in ovine pulmonary vasculature is developmentally regulated

2000 ◽  
Vol 278 (6) ◽  
pp. L1297-L1304 ◽  
Author(s):  
David N. Cornfield ◽  
Connie B. Saqueton ◽  
Valerie A. Porter ◽  
Jean Herron ◽  
Ernesto Resnik ◽  
...  
Keyword(s):  
Acute Hypoxia ◽  
Pulmonary Arteries ◽  
Developmental Changes ◽  
Pulmonary Vasculature ◽  
K Channel ◽  
Mrna Levels ◽  
Channel Activity ◽  
Developmentally Regulated ◽  
Voltage Gated ◽  
Channel Expression

To examine mechanisms underlying developmental changes in pulmonary vascular tone, we tested the hypotheses that 1) maturation-related changes in the ability of the pulmonary vasculature to respond to hypoxia are intrinsic to the pulmonary artery (PA) smooth muscle cells (SMCs); 2) voltage-gated K+(Kv)-channel activity increases with maturation; and 3) O2-sensitive Kv2.1 channel expression and message increase with maturation. To confirm that maturational differences are intrinsic to PASMCs, we used fluorescence microscopy to study the effect of acute hypoxia on cytosolic Ca2+concentration ([Ca2+]i) in SMCs isolated from adult and fetal PAs. Although PASMCs from both fetal and adult circulations were able to sense an acute decrease in O2 tension, acute hypoxia induced a more rapid and greater change in [Ca2+]i in magnitude in PASMCs from adult compared with fetal PAs. To determine developmental changes in Kv-channel activity, the effects of the K+-channel antagonist 4-aminopyridine (4-AP) were studied on fetal and adult PASMC [Ca2+]i. 4-AP (1 mM) caused PASMC [Ca2+]i to increase by 94 ± 22% in the fetus and 303 ± 46% in the adult. Kv-channel expression and mRNA levels in distal pulmonary arteries from fetal, neonatal, and adult sheep were determined through the use of immunoblotting and semiquantitative RT-PCR. Both Kv2.1-channel protein and mRNA expression in distal pulmonary vasculature increased with maturation. We conclude that there are maturation-dependent changes in PASMC O2 sensing that may render the adult PASMCs more responsive to acute hypoxia.

scholarly journals The Interaction of Na+ and K+ in Voltage-gated Potassium Channels

1998 ◽  
Vol 111 (2) ◽  
pp. 195-206 ◽  
Author(s):  
Laszlo Kiss ◽  
David Immke ◽  
Joseph LoTurco ◽  
Stephen J. Korn
Keyword(s):  
Binding Site ◽  
K Channel ◽  
Ionic Selectivity ◽  
K Channels ◽  
Voltage Gated ◽  
High Affinity ◽  
Deactivation Kinetics ◽  
Na Currents ◽  
Apparent Ic50 ◽  
K Currents

Voltage-gated potassium (K+) channels are multi-ion pores. Recent studies suggest that, similar to calcium channels, competition between ionic species for intrapore binding sites may contribute to ionic selectivity in at least some K+ channels. Molecular studies suggest that a putative constricted region of the pore, which is presumably the site of selectivity, may be as short as one ionic diameter in length. Taken together, these results suggest that selectivity may occur at just a single binding site in the pore. We are studying a chimeric K+ channel that is highly selective for K+ over Na+ in physiological solutions, but conducts Na+ in the absence of K+. Na+ and K+ currents both display slow (C-type) inactivation, but had markedly different inactivation and deactivation kinetics; Na+ currents inactivated more rapidly and deactivated more slowly than K+ currents. Currents carried by 160 mM Na+ were inhibited by external K+ with an apparent IC50 <30 μM. K+ also altered both inactivation and deactivation kinetics of Na+ currents at these low concentrations. In the complementary experiment, currents carried by 3 mM K+ were inhibited by external Na+, with an apparent IC50 of ∼100 mM. In contrast to the effects of low [K+] on Na+ current kinetics, Na+ did not affect K+ current kinetics, even at concentrations that inhibited K+ currents by 40–50%. These data suggest that Na+ block of K+ currents did not involve displacement of K+ from the high affinity site involved in gating kinetics. We present a model that describes the permeation pathway as a single high affinity, cation-selective binding site, flanked by low affinity, nonselective sites. This model quantitatively predicts the anomalous mole fraction behavior observed in two different K+ channels, differential K+ and Na+ conductance, and the concentration dependence of K+ block of Na+ currents and Na+ block of K+ currents. Based on our results, we hypothesize that the permeation pathway contains a single high affinity binding site, where selectivity and ionic modulation of gating occur.

Postnatal development of voltage-gated K currents on rat sympathetic neurons

1992 ◽  
Vol 67 (5) ◽  
pp. 1291-1300 ◽  
Author(s):  
S. McFarlane ◽  
E. Cooper
Keyword(s):  
Sympathetic Neurons ◽  
Cell Types ◽  
Neonatal Rat ◽  
Developmental Expression ◽  
Voltage Gated ◽  
Cervical Ganglion ◽  
K Current ◽  
Low Levels ◽  
K Currents

1. We have investigated the developmental expression of three voltage-gated K currents on neonatal rat superior cervical ganglion (SCG) neurons in vivo and in culture: a rapidly inactivating current (IAf), a slowly inactivating current (IAs), and a noninactivating current (IK). 2. On postnatal day 1 neurons (P1), mean peak IAs is 67 +/- 4 (SE) pA/pF, peak IAf is 27 +/- 3 pA/pF, and IK is 14 +/- 3 pA/pF. Over the next wk, there is a switch in the expression of these currents: IAs drops by 40%, whereas IAf increases by greater than 100%; there is no change in IK. On P14 neurons, IAs is 38 +/- 2 pA/pF, IAf is 64 +/- 5 pA/pF, and IK is 12 +/- 1 pA/pF. 3. The change in expression of K currents on SCG neurons over the first 2 postnatal wk is unaffected by preganglionic innervation or by innervation of the targets. 4. To learn more about the factors that affect K current expression on these neurons, we grew SCG neurons in culture without other cell types for various times, and we measured the expression of IAf, IAs, and IK. In culture, the currents remained at their P1 levels for the first 4-7 days. Thereafter, both IAs and IAf decreased to low levels over a period of 2-3 wk. These results suggest that an epigenetic factor(s) is necessary for the expression of IAf and IAf in vivo and that this factor is missing in culture. 5. When IAs and IAf decreased on neurons in culture, we observed a compensatory increase in IK. After 4 wk in culture, IK is fourfold greater than on neurons in vivo. This result suggests that these neurons have intrinsic mechanisms that coordinate the expression of different voltage-gated K currents.

Structural Influence of Hanatoxin Binding on the Carboxyl Terminus of S3 Segment in Voltage-Gated K + -Channel Kv2.1

2002 ◽  
Vol 8 (2) ◽  
pp. 79-85 ◽  
Author(s):  
P. T. Huang ◽  
T. Y. Chen ◽  
L. J. Tseng ◽  
K. L. Lou ◽  
H. H. Liou ◽  
...  
Keyword(s):  
Carboxyl Terminus ◽  
K Channel ◽  
Voltage Gated ◽  
S3 Segment ◽  
Structural Influence
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