心肌肽素对豚鼠心室肌细胞L型钙通道的影响

目的研究心肌肽素对豚鼠心室肌细胞L型钙通道的影响,探讨心肌肽素在离子通道水平的药理作用机制。方法用急性酶解分离法获得豚鼠心室肌细胞,标准的全细胞膜片钳技术记录L型钙电流(ICa-L)。结果心肌肽素1、5、10、50、100、500 mg.L-1使豚鼠心室肌细胞ICa-L分别增加(5±4)%、(21±5)%、(30±5)%、(55±8)%、(76±11)%、(80±9)%,半最大效应浓度(EC50)为(18±6)mg.L-1。心肌肽素50 mg.L-1使ICa-L激活时间(TTP)从(6.7±0.9)m s缩短为(5.9±0.7)m s(P<0.01);使ICa-L电流密度-电压曲线下移,但激活电压、峰电压和I-V曲线的形状不变;激活曲线向负电压方向变化,半数激活电压从(-4.3±0.4)mV减少至(-8.6±0.4)mV(P<0.05);不影响稳态失活曲线和稳态失活后恢复曲线。结论心肌肽素浓度依赖性增强豚鼠心室肌细胞ICa-L。

Effects of cardiomyopeptidin on L-type calcium channels in ventricular myocytes of guinea pigs

Aim To determine the effect of cardiomyopeptidin on L-type calcium channels in ventricular myocytes of guinea pigs and to explore the mechanism of cardiomyopeptidin on the ionic channel level.Methods Single ventricular myocytes of guinea pigs were obtained with enzymatic dissociation method.The whole-cell patch-clamp recording technique was used to record the change of L-type calcium currents(I_(Ca-L)).Results Cardiomyopeptidin(1,5,10,50,100 and 500 mg·L~(-1)) increased I_(Ca-L) in a dose-dependent manner,the increasing rates were(5±4)%,(21±5)%,(30±5)%,(55±8)%,(76±11)% and(80±9)% respectively.The half maximal effect concentration(EC_(50)) was(18±6) mg·L~(-1).In the presence of cardiomyopeptidin(50 mg·L~(-1)),the time to peak(TTP) of I_(CaL) was decreased from(6.7±0.9) ms to(5.9±0.7) ms(P<0.01).The current density-voltage curve of I_(Ca-L) was moved down in the presence of cardiomyopeptidin 50 mg·L~(-1),but the active potential,the peak potential,and the shape of the curve had no changes.The activation curve of I_(Ca-L) was moved to more negativepotential in the presence ofcardiomyopeptidin (50 mg·L~(-1)),with a half active potential(V_(0.5)) of(-4.3±0.4) mV compared with that of(-8.6±0.4) mV in the control(P<0.05).The steady inactivation curve of I_(Ca-L) and the steady inactivation recovery curve of I_(Ca-L) were not affected by cardiomyopeptidin(50 mg·L~(-1)).Conclusion Cardiomyopeptidin increases I_(Ca-L) of guinea pig ventricular myocytes in a concentration-dependent manner.