Effects of chloride ion substitutes and chloride channel blockers on the transient outward current in rat ventricular myocytes

The modulation of the transient outward K+ current (Ito) by divalent cations was studied in enzymatically isolated rat ventricular myocytes with the whole cell patch-clamp technique. At holding potentials negative to -70 mV, 1 mM Cd2+ suppressed Ito, whereas, at potentials positive to -50 mV, the current was augmented. These effects were caused by shifts in the voltage dependence of both activation and inactivation of Ito toward more positive potentials. Cd2+ also slowed the activation kinetics of Ito by shifting the voltage dependence of its rate of activation, but the rate of inactivation was unaffected. Other divalent cations produced similar shifts but at markedly different concentrations. Thus, in the millimolar range, a rightward shift of approximately 20 mV was produced by 3 Co2+, 5 Ni2+, and 10 Ca2+, whereas 10 microM concentrations of Cu2+ and Zn2+ produced equivalent shifts. Similar effects were seen in hippocampal neurons with micromolar concentrations of Zn2+. Thus divalent cations have marked and specific effects on the kinetics and voltage dependence of Ito and may serve as a regulatory mechanism in its activation, particularly in cells with resting potentials positive to -60 mV.

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A surprising effect of the sulfonylurea tolbutamide in rat ventricular myocytes: Inhibition of the transient outward current Lefevre I.A., Coulombe A. & Coraboeuf E. Laboratoire de Physiologie Compar�e, Universit� Paris XI, Orsay, France

Journal of Molecular and Cellular Cardiology ◽

10.1016/0022-2828(91)90336-k ◽

1991 ◽

Vol 23 ◽

pp. S38

Keyword(s):

Ventricular Myocytes ◽

Outward Current ◽

Transient Outward Current ◽

Rat Ventricular Myocytes ◽

Surprising Effect

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Transient outward current in human and rat ventricular myocytes

Cardiovascular Research ◽

10.1093/cvr/27.9.1662 ◽

1993 ◽

Vol 27 (9) ◽

pp. 1662-1669 ◽

Cited By ~ 88

Author(s):

E. Wettwer ◽

G. Amos ◽

J. Gath ◽

H.-R. Zerkowski ◽

J.-C. Reidemeister ◽

...

Keyword(s):

Ventricular Myocytes ◽

Outward Current ◽

Transient Outward Current ◽

Rat Ventricular Myocytes

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Tedisamil inactivates transient outward K+ current in rat ventricular myocytes

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1989.257.5.h1746 ◽

1989 ◽

Vol 257 (5) ◽

pp. H1746-H1749 ◽

Cited By ~ 4

Author(s):

I. D. Dukes ◽

M. Morad

Keyword(s):

Ventricular Myocytes ◽

Sodium Current ◽

Outward Current ◽

Cell Voltage ◽

Transient Outward Current ◽

Dependent Manner ◽

Rat Ventricular Myocytes ◽

K Current ◽

New Type ◽

Inwardly Rectifying

The action of tedisamil, a new bradycardiac agent with antiarrhythmic properties, was investigated in single rat ventricular myocytes using the whole cell voltage-clamp technique. Under current clamp conditions, 1-20 microM tedisamil caused marked prolongations of the action potential. Over the same concentration range, in voltage-clamped myocytes, tedisamil suppressed the transient outward current (ito) and enhanced its inactivation in a dose-dependent manner. The half-maximal dose for the effect of tedisamil on ito was approximately 6 microM. Tedisamil had no significant effects on the inwardly rectifying potassium current and calcium current but did suppress the sodium current at concentrations greater than 20 microM. Our findings suggest that tedisamil represents a new type of antiarrhythmic agent that primarily suppresses the transient outward K+ current.

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