苄基四氢帕马丁对豚鼠心房单细胞延迟外向钾电流的电压依赖性抑制作用

Voltage-dependent inhibition of the delayed outward potassium current by benzyltetrahydropalmatine in isolated atrial single cell of guinea pig heart

本文采用膜片钳封接技术，在豚鼠心房单细胞研究了苄基四氢帕马丁对动作电位和跨膜离子流的作用。结果发现，该药可显著地延长心房细胞的动作电位时程，并具有频率一浓度依赖性，但是，对动作电位时程复极到２０％时的值影响不明显，而且亦呈频率一浓度依赖性特异地抑制延迟外向钾电流和外向尾电流。去极化至－２０ｍＶ到＋６０ｍＶ间，这种抑制作用较强。不过药物对保持电流无明显影响。提示，该药抗心律失常和延长动作电位作用的主要机制是抑制延迟外向钾电流和尾电流。

In this paper, we studied the effect ofbenzyltetrahydropalmatine (BTHP) on membrane cur-rents using the isolated single guinea pig atrial cell. Thetight-seal cell clamp technique was used. In the cur-rent clamp condition, BTHP prolonged significantly90% of the atnal cell's action potential duration(APD90) at 0.1, 1 and 3.3 Hz stimulated frequency.However, the drug does not markedly influence onAPD20. The agent prolonged APD with frequency-and concentration-dependence. This is very beneficialfor patient suffered from myocardial ischemia. De-layed outward K+ current (IK) and outward tail cur-rent were specifically inhibited by BTHP in a frequen-cy-and concentration-dependent fashion. BTHP in-hibited IK more strongly when the membrane poten-tial becomes more positive from-20 mV to +60 mV.In the study, the drug had not affect on the holdingcurrent. The results strongly suggest that the principalmechanism of BTHP in antiarrhythmic action andprolonging APD is to inhibit voltage-dependent K+current.