EFFECTS OF AMIODARONE AND DESETHYLAMIODARONE ON THE INWARD RECTIFYINGPOTASSIUM CURRENT (I-K1) IN RABBIT VENTRICULAR MYOCYTES

We examined the effects of amiodarone (AMI) and desethylamiodarone (DA M) on whole-cell inward rectifying potassium current (I-K1) in freshly isolated adult rabbit ventricular myocytes by using the whole-cell vo ltage-clamp technique, as an index of their effects on resting membran e resistance (R-m). Under control conditions, the current showed a str ong inward rectification with a maximal inward current measured at -13 0 mV of -26.4 +/- 1.3 pA/pF and a maximal outward current measured at -50 mV of 3.5 +/- 0.3 pA/pF The current also exhibit a time-dependent activation, with a time constant of activation (tau(a)) that increased with depolarization. The maximal slope conductance normalized to cell capacitance was 0.509 +/- 0.019 nS/pF After exposure to both DAM (50 mu M; n = 8) and AMI (50 mu M; n = 7). rapid decrease in inward I-K1 w as observed. Block was restricted almost exclusively to the inward com ponent. DAM caused a significant reduction of the maximal inward curre nt (-20.0 +/- 2.0 pA/pF; p < 0.05), whereas AMI induced an even greate r reduction of the same component (-14.1 +/- 1.2 pA/pF; p < 0.05 with respect to control and to DAM). The outward component of IE;I was not changed by either AMI or DAM (4.0 +/- 0.3 pA/pF and 3.4 +/- 0.4 pA/pF respectively). AMI and DAM also decreased the maximal slope conductanc e significantly (0.297 +/- 0.019 nS/pF and 0.421 +/- 0.038 nS/pF, resp ectively). In addition, AMI but not Dam significantly increased the ta u(a). However, the voltage dependence of the acceleration of tau(a), r emained unchanged after both AMI and DAM exposure. These results allow us to conclude that AMI may induce a greater increase in the resting R-m than its main metabolite. This effect may counterbalance, at least in part, the conduction slowing due to its sodium channel-blocking pr operties.