Amiodarone blocks the inward rectifier potassium channel in isolated guinea pig ventricular cells
We examined the effects of amiodarone (5-20 microM) on both whole-cell inward rectifier potassium current (IK1) and single IK1 channel activity in isolated guinea pig ventricular myocytes using patch-clamp techniques. In whole-cell voltage-clamp experiments (n = 8), amiodarone (10-20 microM) caused...
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Published in | The Journal of pharmacology and experimental therapeutics Vol. 269; no. 3; pp. 1213 - 1219 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Bethesda, MD
American Society for Pharmacology and Experimental Therapeutics
01.06.1994
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Subjects | |
Online Access | Get full text |
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Summary: | We examined the effects of amiodarone (5-20 microM) on both whole-cell inward rectifier potassium current (IK1) and single
IK1 channel activity in isolated guinea pig ventricular myocytes using patch-clamp techniques. In whole-cell voltage-clamp
experiments (n = 8), amiodarone (10-20 microM) caused only a small reduction of outward current at -50 mV (12 +/- 6%, no significant
difference, N.S.). However, inward current was significantly reduced at -120 mV (21 +/- 7%; P < .05). When CdCl2 (100 microM)
and tetrodotoxin (10 microM) were used to block inward Ca++ and Na+ current, respectively, amiodarone significantly reduced
IK1 in both the inward (14 +/- 5% at -120 mV; P < .02) and outward (12 +/- 5% at -50 mV; P < .05; n = 11) directions. However,
block required high drug concentrations (10-20 microM) and was slow in onset. In contrast, amiodarone did not affect membrane
current when IK1 had been previously blocked by Ba++ (5 mM). In inside-out patch-clamp experiments, amiodarone (5 microM)
reduced single IK1 channel open probability by increasing interburst interval (from 0.6 +/- 0.03 to 3.1 +/- 0.9 sec; n = 5;
P < .05) with no significant difference in the duration of mean open and closed times or the number of shut events within
a burst. The net result was that there was only a small change in both burst duration and single-channel kinetics within a
burst. Complete channel block occurred after the increase in interburst interval (n = 6 of six cells). |
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ISSN: | 0022-3565 1521-0103 |