Salata J J, Jalife J
J Pharmacol Exp Ther. 1982 Jan;220(1):157-66.
Dantrolene sodium at concentrations between 8.8 and 35.1 microM produced rather selective changes in the electrophysiological properties of isolated dog Purkinje fibers. The action potential duration at 90% repolarization and effective refractory period of normally polarized fibers were increased in a dose- and frequency-dependent fashion. The plateau phase of the action potential was significantly depressed and this effect coincided with a marked decrease in the strength of contraction. Dantrolene sodium had no significant effect on resting membrane potential, upstroke velocity of phase O, conduction velocity or pacemaker activity of Purkinje fibers. Dantrolene diminished or abolished "slow response" action potentials produced by superfusion with 18 mM K+ Tyrode's solution containing 10(-7) M isoproterenol. Drug effects took 10 to 15 min to become apparent, reached a steady-state after 45 to 60 min and were not reversible even after 2 hr of washout with drug-free Tyrode's solution. In contrast, increasing the [Ca++]0 produced nearly a complete reversal of the dantrolene-induced changes. These results suggest that dantrolene produces its effects by interfering with the slow inward current. Thus, dantrolene may be similar in action to other slow channel blocking agents, such as verapamil, and may be useful as an antiarrhythmic agent.
浓度在8.8至35.1微摩尔之间的丹曲林钠对离体犬浦肯野纤维的电生理特性产生了相当选择性的变化。正常极化纤维在90%复极化时的动作电位持续时间和有效不应期以剂量和频率依赖的方式增加。动作电位的平台期明显降低，这种效应与收缩强度的显著降低同时出现。丹曲林钠对浦肯野纤维的静息膜电位、O期除极速度、传导速度或起搏活动没有显著影响。丹曲林减少或消除了用含10(-7)M异丙肾上腺素的18mM K+ 台氏液灌流产生的“慢反应”动作电位。药物作用在10至15分钟后开始显现，45至60分钟后达到稳态，即使在用无药台氏液冲洗2小时后也不可逆。相反，增加[Ca++]0几乎完全逆转了丹曲林诱导的变化。这些结果表明，丹曲林通过干扰慢内向电流产生其作用。因此，丹曲林的作用可能与其他慢通道阻滞剂如维拉帕米相似，并且可能作为一种抗心律失常药物有用。
