Nishimura M, Huan R M, Habuchi Y, Tsuji Y, Nakanishi T, Watanabe Y
Cardiovascular Institute, Fujita Gakuen Health University School of Medicine, Aichi, Japan.
J Pharmacol Exp Ther. 1988 Feb;244(2):780-8.
The effects of quinidine (0.01-20 micrograms/ml) on spontaneous action potentials and membrane current systems of the rabbit atrioventricular node were studied. At therapeutic concentrations, this drug decreased the action potential amplitude, the maximal diastolic potential, the threshold potential as well as the maximal rate of depolarization and showed a negative chronotropic action. Quinidine, at 5 micrograms/ml, decreased the peak slow inward current by 30.2%, increased its time constant of inactivation by 27.3%, shifted the steady-state inactivation curve toward more negative membrane potentials by 2.8 mV and decreased its fully activated current. Quinidine exerted not only resting but also use-dependent blocking actions on the slow inward current. The depression of the action potential upstroke can thus be explained by the reduction in this current. The outward K+ tail current was decreased by 65.4% and its deactivation time constant was increased by 19.0%. These effects may have contributed to the prolongation of the action potential duration, the reduction in the maximal diastolic potential and the slowing of diastolic depolarization. Quinidine shifted the steady-state activation curve for this K+ current toward hyperpolarization by as much as 7.8 mV. It decreased the hyperpolarization-activated inward current by 16.3% and increased its activation time constant by 10.1%, but this current appeared to play a small role in reducing the rate of diastolic depolarization. These observations indicate that, depending upon dose, quinidine has the potential to decrease all of the time- and voltage-dependent ionic currents in atrioventricular nodal cells.
研究了奎尼丁（0.01 - 20微克/毫升）对兔房室结自发动作电位和膜电流系统的影响。在治疗浓度下，该药物降低动作电位幅度、最大舒张电位、阈电位以及最大去极化速率，并表现出负性变时作用。5微克/毫升的奎尼丁使慢内向电流峰值降低30.2%，使其失活时间常数增加27.3%，将稳态失活曲线向更负的膜电位方向移动2.8毫伏，并降低其完全激活电流。奎尼丁不仅对慢内向电流有静息阻断作用，还具有使用依赖性阻断作用。动作电位上升支的抑制因此可以用该电流的减少来解释。外向K⁺尾电流降低了65.4%，其失活时间常数增加了19.0%。这些效应可能导致动作电位持续时间延长、最大舒张电位降低和舒张期去极化减慢。奎尼丁使该K⁺电流的稳态激活曲线向超极化方向移动多达7.8毫伏。它使超极化激活内向电流降低16.3%，并使其激活时间常数增加10.1%，但该电流在降低舒张期去极化速率方面似乎起的作用较小。这些观察结果表明，根据剂量不同，奎尼丁有可能降低房室结细胞中所有与时间和电压相关的离子电流。
