抗心律失常药物作用的新靶点

New targets of antiarrhythmic drugs

目的 寻找抗心律失常药物作用的新靶点。方法 应用全细胞膜片钳技术记录乌头碱对大鼠心肌细胞动作电位时程的作用 ,分别给予奎尼丁、维拉帕米处理比较二者对动作电位时程的影响。结果 ①应用 1μmol·L- 1乌头碱使大鼠单个心肌细胞动作电位复极 5 0 %时程 (APD50 )从给药前 (5 7.2 5± 13.85 )ms增加到 (70 .5 1± 12 .4 4 )ms(n =8,P <0 .0 1) ,动作电位复极 90 %时程 (APD90 )从给药前 (86 .2 5± 2 4 .92 )ms增加到 (114 .12± 6 .81)ms(n =8,P <0 .0 5 )。② 10 μmol·L- 1 奎尼丁使乌头碱处理的大鼠心肌细胞APD50 进一步延长至 (111.6 3± 37.2 4 )ms(n =4 ,P <0 .0 5 ) ,使APD90 延长至 (2 0 1.75± 6 9.75 )ms(n =4 ,P <0 .0 1)。③ 10 μmol·L- 1 维拉帕米使乌头碱诱发的动作电位延长有所恢复 ,APD50 缩短至 (5 1.6 3± 15 .11)ms(n =4 ,P <0 .0 1) ,APD90 缩短至 (91.2 5± 11.0 6 )ms(n =4 ,P <0 .0 5 )。结论 使动作电位时程延长将诱发心律失常 ,使动作电位时程恢复近正常是抗心律失常药物作用的新靶点。

Objective To search the new targets of antiarrhythmic drug. Methods Effects of quinidine and verapamil on the alteration of action potential duration induced by aconitine were studied by use of the whole cell patch clamp techniques in rat ventricular myocytes.Results Aconitine potently prolonged the 50% repolarization of action potential duration(APD 50 ) from (57.25±13.85)ms to (70.51±12.44)ms( n =8, P < 0.01 ),prolonged the 90% repolarization of action potential duration (APD 90 ) from (86.25±24.92)ms to (114.12±6.81)ms( n =8, P <0.05). Quinidine 10μmol·L -1 aggravated the prolongation of APD 50 and APD 90 induced by aconitine to (111.63±37.24)ms( n =4, P <0.05) and (201.75±69.75)ms( n =4, P <0.01) respectively. Verapamil 10μmol·L -1 shortened the prolongation of APD 50 and APD 90 induced by aconitine to (51.63±15.11)ms( n =4, P <0.01) and (91.25±11.06)ms( n =4, P <0.05)respectively and recovered to the normal condition. Conclusion Prolongation of the action potential duration (APD) will induce arrhythmias and recover of APD is the target of antiarrhythmic drug.