Amiodarone inhibits cardiac ATP-sensitive potassium channels

Amiodarone Inhibition of Cardiac K-ATP Channels. Introduction: ATP-sensitiv e K+ channels (K-ATP) are expressed abundantly in cardiovascular tissues. B locking this channel in experimental models of ischemia can reduce arrhythm ias. We investigated the acute effects of amiodarone on the activity of car diac 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 a nd a pipette potential of +40 mV), Amiodarone inhibited K-ATP channel activ ity in a concentratron-dependent manner. After 60 seconds of exposure to am iodarone, the fraction of mean patch current relative to baseline current w as 1.0 +/- ;.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 mu M amiodarone, respectively (I C50 = 2.3 mu M). ATP sensitivity was greater in the presence of amiodarone (EC50 = 13 +/- 0.2 mu M in the presence of 10 mu M amiodarone vs 43 +/- 0.1 mu M in controls, n = 5; P < 0.05), Kinetic analysis showed that open and short closed intervals (bursting activity) were unchanged by 1 mu M amiodar one, whereas interburst closed intervals were prolonged. Amiodarone also in hibited whole cell K-ATP channel current (activated by 100 mu M bimakalim), After a 10-minute application of amiodarone (10 mu M), relative current wa s 0.71 +/- 0.03 vs 0.92 +/- 0.09 in control (P < 0.03), Conclusion: Amiodarone rapidly inhibited K-ATP channel activity by both pro moting channel closure and increasing ATP sensitivity, These actions may co ntribute to the antiarrhythmic properties of amiodarone.