舒必利致心律失常的电生理研究

Electrophysiological study on arrhythmia induced by sulpiride

目的:观察不同浓度舒必利对缺血兔心浦肯野纤维动作电位的影响及舒必利对豚鼠心室肌细胞钠通道电流的作用。方法:采用标准微电极技术,观察不同浓度(1～100μmol/L)舒必利对模拟缺血液灌流的离体兔心浦肯野纤维动作电位0期去极化幅值(APA)、最大除极速率(Vmax)、有效不应期(ERP)及90%动作电位时程(APD90)的影响。应用酶解法分离豚鼠单个心室肌细胞,应用全细胞膜片钳技术记录舒必利对钠通道电流(INa)的影响。结果:不同浓度的舒必利对缺血兔浦肯野纤维动作电位的APA和APD90无明显影响,对Vmax有降低趋势。舒必利(3～300μmol/L)浓度依赖性地抑制INa(IC50=10.79μmol/L,测试电压-35 mV)。10μmol/L舒必利降低了INa的最大电导gmax,使半激活、失活电压负值分别减小了1.91 mV(P<0.01)和5.22 mV(P<0.01);恢复时间常数增加,但最大激活电流可以基本恢复至给药前。结论:舒必利可轻度逆转缺血液灌流造成的心浦肯野纤维动作电位缩短,并浓度依赖性地抑制钠电流,舒必利作用于钠通道的失活态。

AIM： To observe the effects of different concentrations of sulpiride （1, 3, 10, 30, 100 μmol/L） on action potentials of rabbit cardiac purkinje fibers under ischemic conditions, and the effects of sulpiride on fast sodium current （Ina） of ventricular myocytes in guinea pigs. METHODS： By standard microelectrode technique, the effects of different concentrations （1 - 100 μmol/L） sulpiride on action potential parameters （APA）, the depolarization velocity （ Vmax ）, effective refractory period （ERP）and 90% action potential duration （APD50 ） of rabbit cardiac purkinje fibers were observed, in which tissues were peffused by simulated ischemic fluid. Single ventricular myocytes in guinea pigs were isolated with enzymatic dissociation method and the effects of sulpiride on INa of ventricular myocytes were recorded using whole-cell patch clamp technique. RESULTS ： The effects of different concentrations of sulpiride on the ischemic cardiac purkinje fibers APA, APDgo had no statistical differ-ence, but the Vmax was decreased. Sulpiride （3 - 300 μmol/L） inhibited INa in a concentration dependent manner （IC50 = 10.79 μmol/L, the test potential was -35 mV）. Sulpiride （10 μmol/L） reduced the maximum conductance （ gmax ） of INa, and the activation and inactivation voltage of INa were decreased by 1.91 mV, 5.22 mV（ P 〈 0.01）, respectively, the coincidnece time constant was increased, while the maximum activated current of INa recovered to that before administration. CONCLUSION： Sulpiride could lightly reverse the shortening of action potential in cardiac purkinje fibers induced by ischemia reperfusion. Sulpiride also inhibits INa in a concentration dependent manner. Sulpiride probably affects the inactivated-state of sodium channels.