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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。
Objective: To observe the effects of different concentrations of sulpiride on action potentials of Purkinje fibers in rabbits and the effect of sulpiride on sodium channel current in guinea pig ventricular myocytes. Methods: Standard microelectrode technique was used to observe the amplitude of depolarization amplitude (APA), the maximum depolarization rate (APA), and the maximum depolarization rate (APA) in different concentrations (1- 100μmol / (Vmax), effective refractory period (ERP) and 90% action potential duration (APD90). Single guinea pig ventricular myocytes were isolated by enzymatic method and the effect of sulpiride on sodium channel current (INa) was recorded using whole-cell patch clamp technique. RESULTS: Different concentrations of sulpiride had no significant effect on APA and APD90 in the action potentials of Purkinje fibers in ischemic rabbit, but decreased in Vmax. Sulpiride (3 ~ 300μmol / L) inhibited INa concentration-dependently (IC50 = 10.79μmol / L, test voltage -35 mV). 10μmol / L sulpiride reduced the maximum conductance gmax of INa, and decreased the values of half activation and inactivation by 1.91 mV (P <0.01) and 5.22 mV (P <0.01) respectively; the recovery time constant increased but the maximal activation current Can be basically restored to the medication before. CONCLUSIONS: Sulpiride mildly reverses the shortening of action potential of heart Purkinje fibers caused by ischemic perfusion and regulates sodium currents in a concentration-dependent manner. Sulpiride acts on the inactivation of sodium channels.