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

Abstract

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 50µmol/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 (IK), slowly activating delayed rectifier outward K + current (IKs), transient outward K + current (Ito )a nd rectifier K + current (IK1). Compared with the control group, the current density of IK ,I K1 and Ito were all decreased in hypertrophied myocytes group. Hyper-concentration of amiodarone (10 and 50µmol/l) inhibited Ito 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 IK1 neither the control nor hypertrophied myocytes group. 10µmol/l amiodarone inhibited IKs 23.3% ± 6.2% in the control group and 50.1% ± 9.8% in the hypertrophied myocytes group. Ito and IKs appeared difference affection of amiodarone’s action on both groups. IKs in hypertrophy group was higher than that in control, whereas Ito was lower in hypertrophy group. We concluded amiodarone do inhibit Ito and IK in rat normal and hypertrophied cardiomyocytes. Amiodarone application should be treated difference between hypertrophied heart and normal heart.