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Amiodarone Inhibits Cardiac ATP‐Sensitive Potassium Channels
Author(s) -
HOLMES DOUGLAS S.,
SUN ZHUOQIAN,
PORTER LISA M.,
BERNSTEIN NEIL E.,
CHINITZ LARRY A.,
ARTMAN MICHAEL,
COETZEE WILLIAM A.
Publication year - 2000
Publication title -
journal of cardiovascular electrophysiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.193
H-Index - 138
eISSN - 1540-8167
pISSN - 1045-3873
DOI - 10.1111/j.1540-8167.2000.tb01762.x
Subject(s) - amiodarone , medicine , potassium channel , potassium , antiarrhythmic agent , patch clamp , electrophysiology , anesthesia , pharmacology , endocrinology , chemistry , atrial fibrillation , heart disease , organic chemistry
Amiodarone Inhibition of Cardiac K ATP Channels. Introdttction: ATP‐sensitive K + channels (K ATP ) are expressed abundantly in cardiovascular tissues. Blocking this channel in experinuntal models of ischemia can reduce arrhythmias. We investigated the acute effects of amiodarone on the activity of cardiac sarcolemmal K ATP channels and their sensitivity to ATP. Methods and Results: Single K ATP channel activity was recorded using inside‐out patches from rat ventricular myocytes (symmetric 140 mM K + solutions and a pipette potential of +40 mV). Amiodarone inhibited K ATP channel activity in a concentration‐dependent manner. Alter 60 seconds of exposure to amiodarone, the fraction of mean patch current relative to baseline current was 1.0 ± 0.05 (n = 4), 0.8 ± 0.07 (n = 4), 0.6 ± 0.07 (n = 5), and 0.2 ± 0.05 (n = 7) with 0, 0.1, 1.0. or 10 μM amiodarone, respectively (IC 50 = 2.3 μM). ATP sensitivity was greater in the presence of amiodarone (EC 50 = 13 ± 0.2 μM in the presence of 10 μM amiodarone vs 43 ± 0.1 μM in contnils, n = 5; P < 0.05). Kinetic analysis showed that open and short closed intervals (bursting activity) were unchanged by 1 μM amiodarone, whereas interburst closed intervals were prolonged. Amiodarone also inhibited whole cell K ATP . channel current (activated by 100 μM bimakalim). After a 10‐minute application of amiodarone (10 μM), relative current was 0.71 ± 0.03 vs 0,92 ± 0.09 in control (P < 0.03). Conclusion: Amiodarone rapidly inhibited K ATP channel activity by both promoting channel closure and increasing ATP sensitivity. These actions may contribute to the antiarrhythmic properties of amiodarone.