Sato R, Koumi S, Singer D H, Hisatome I, Jia H, Eager S, Wasserstrom J A
Reingold ECG Center, Department of Medicine, Northwestern University Medical School, Chicago, Illinois.
J Pharmacol Exp Ther. 1994 Jun;269(3):1213-9.
We examined the effects of amiodarone (5-20 microM) on both whole-cell inward rectifier potassium current (IK1) and single IK1 channel activity in isolated guinea pig ventricular myocytes using patch-clamp techniques. In whole-cell voltage-clamp experiments (n = 8), amiodarone (10-20 microM) caused only a small reduction of outward current at -50 mV (12 +/- 6%, no significant difference, N.S.). However, inward current was significantly reduced at -120 mV (21 +/- 7%; P < .05). When CdCl2 (100 microM) and tetrodotoxin (10 microM) were used to block inward Ca++ and Na+ current, respectively, amiodarone significantly reduced IK1 in both the inward (14 +/- 5% at -120 mV; P < .02) and outward (12 +/- 5% at -50 mV; P < .05; n = 11) directions. However, block required high drug concentrations (10-20 microM) and was slow in onset. In contrast, amiodarone did not affect membrane current when IK1 had been previously blocked by Ba++ (5 mM). In inside-out patch-clamp experiments, amiodarone (5 microM) reduced single IK1 channel open probability by increasing interburst interval (from 0.6 +/- 0.03 to 3.1 +/- 0.9 sec; n = 5; P < .05) with no significant difference in the duration of mean open and closed times or the number of shut events within a burst. The net result was that there was only a small change in both burst duration and single-channel kinetics within a burst. Complete channel block occurred after the increase in interburst interval (n = 6 of six cells).(ABSTRACT TRUNCATED AT 250 WORDS)
我们采用膜片钳技术，研究了胺碘酮（5 - 20微摩尔）对分离的豚鼠心室肌细胞全细胞膜内向整流钾电流（IK1）及单个IK1通道活性的影响。在全细胞膜电压钳实验中（n = 8），胺碘酮（10 - 20微摩尔）在-50毫伏时仅使外向电流稍有降低（12±6%，无显著差异，NS）。然而，在-120毫伏时内向电流显著降低（21±7%；P <.05）。当分别用氯化镉（100微摩尔）和河豚毒素（10微摩尔）阻断内向钙电流和钠电流时，胺碘酮在内向（-120毫伏时为14±5%；P <.02）和外向（-50毫伏时为12±5%；P <.05；n = 11）方向均显著降低IK1。然而，这种阻断需要高药物浓度（10 - 20微摩尔）且起效缓慢。相比之下，当IK1先前已被钡离子（5毫摩尔）阻断时，胺碘酮不影响膜电流。在膜内面向外膜片钳实验中，胺碘酮（5微摩尔）通过增加爆发间期（从0.6±0.03秒增至3.1±0.9秒；n = 5；P <.05）降低单个IK1通道开放概率，而平均开放和关闭时间的持续时间或一次爆发内关闭事件的数量无显著差异。最终结果是，一次爆发内的爆发持续时间和单通道动力学仅有微小变化。爆发间期增加后发生完全通道阻断（六个细胞中有六个细胞，n = 6）。（摘要截短于250字）
