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Title:OPEN-STATE UNBLOCK CHARACTERIZES ACUTE INHIBITION OF IKS POTASSIUM CURRENT BY AMIODARONE IN GUINEA-PIG VENTRICULAR MYOCYTES
DOI No:10.1142/9789812702234_0074
Source:ADVANCES IN ELECTROCARDIOLOGY 2004 (pp 278-281)
Author(s):DIMITAR ZANKOV
Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Otsu, Shiga, 520-2192, Japan

WEI-GUANG DING
Department of Physiology, Shiga University of Medical Science, Otsu, Shiga, 520-2192, Japan

HIROSHI MATSUURA
Department of Physiology, Shiga University of Medical Science, Otsu, Shiga, 520-2192, Japan

MINORU HORIE
Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Otsu, Shiga, 520-2192, Japan

Abstract:Acute action of amiodarone on the slowly delayed rectifier K current (IKs) was investigated in guinea-pig ventricular myocytes by means of whole-cell patch-clamp method. Amiodarone activity was also examined on maximally potentiated IKs by β-adrenoceptor activation. Amiodarone blocked IKs in a concentration-dependent manner and exerted a more potent action when IKs was activated by shorter pulse durations. An envelope of tails test demonstrated that the degree of amiodarone inhibition on IKs was gradually attenuated during membrane depolarization, thus supporting the presence of open channel unblock. Amiodarone also blocked maximally stimulated IKs by 1 μM isoprenaline to an extent similar to control when IKs was activated by depolarizing pulses = 2000 ms. It is concluded that amiodarone acutely blocks IKs with characteristics related to open channel unblock. Phosphorylation of channel proteins by protein kinase A appears to affect minimally IKs inhibition.
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