The class III anti-arrhythmic agent, amiodarone, inhibits voltage-dependent K<SUP>+</SUP> channels in rabbit coronary arterial smooth muscle cells

초록

We examined the inhibitory effect of amiodarone, a class III anti-arrhythmic agent, on voltage-dependent K+ (Kv) currents in freshly isolated rabbit coronary arterial smooth muscle cells, using a whole-cell patch clamp technique. Amiodarone inhibited Kv currents in a concentration-dependent manner, with a half-maximal inhibitory concentration (IC50) value of 3.9 +/- 1.44 mu M and a Hill coefficient of 0.45 +/- 0.14. Amiodarone did not have a significant effect on the steady-state activation of Kv channels, but shifted the inactivation current toward a more negative potential. Application of consecutive pulses progressively augmented the amiodarone-induced Kv channel inhibition. Another class III anti-arrhythmic agent, dofetilide, did not inhibit the Kv current or change the inhibitory effect of amiodarone on Kv channels. Therefore, these results strongly suggest that amiodarone inhibits Kv currents in a concentration- and state-dependent manner.

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