ISSN:
1540-8167
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Amiodarone Inhibition of Cardiac KATP Channels. Introdttction: ATP-sensitive K+ channels (KATP) 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 KATP channels and their sensitivity to ATP.Methods and Results: Single KATP 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 KATP 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 (IC50= 2.3 μM). ATP sensitivity was greater in the presence of amiodarone (EC50= 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 KATP. 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 KATP channel activity by both promoting channel closure and increasing ATP sensitivity. These actions may contribute to the antiarrhythmic properties of amiodarone.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1540-8167.2000.tb01762.x
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