The Effect of Amiodarone on K⁺ Channel Current in the Normal and Hypertrophied Rat Heart

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The basis for the unique effectiveness of amiodarone treatment on cardiac arrhythmias is incompletely understood. We investigated and compared the effects of amiodarone on K⁺ channels of hypertrophied ventricular myocytes with normal ventricular myocytes in rats. The pressure overload hypertrophy models of rats were established by partial ligation of ascending aorta for 4 weeks. Ventricular myocytes were exposed to 1, 10 and 50 μmol/l amiodarone, and whole cell patch-clamp technique was used to study the effects of amiodarone on outward currents, such as delayed rectifier outward K⁺ current (I_K), slowly activating delayed rectifier outward K⁺ current (I_Ks), transient outward K⁺ current (I_to) and rectifier K⁺ current (I_K1). Compared with the control group, the current density of I_K, I_K1 and I_to were all decreased in hypertrophied myocytes group. Hyper-concentration of amiodarone (10 and 50 μmol/l) inhibited I_to of the control group (37.5%±5.8% and 54.3%±5.7%) and the hypertrophied myocytes group (9.3%±2.3% and 22.8%±3.0%), but had effect on I_K1 neither the control nor hypertrophied myocytes group. 10 μmol/l amiodarone inhibited I_Ks 23.3%±6.2% in the control group and 50.1%±9.8% in the hypertrophied myocytes group. I_to and I_Ks appeared difference affection of amiodarone's action on both groups. I_Ks in hypertrophy group was higher than that in control, whereas I_to was lower in hypertrophy group. We concluded amiodarone do inhibit I_to and I_K in rat normal and hypertrophied cardiomyocytes. Amiodarone application should be treated difference between hypertrophied heart and normal heart.