Hasin Y, Barry W H
Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
J Mol Cell Cardiol. 1987 Sep;19(9):853-63. doi: 10.1016/s0022-2828(87)80614-4.
In order to examine possible differences in mechanisms of action of nifedipine and verapamil, simultaneous recordings of membrane potential and cell motion were made during exposure of cultured chick embryo ventricular cells to these drugs. Both verapamil and nifedipine produced a rapid negative inotropic effect and excitation-contraction coupling delay presumably related to the ability of both agents to inhibit Ca2+ influx via the slow Ca channel, and thus decrease the [Ca2+]i transient. However, for an equivalent negative inotropic effect, verapamil produced relatively more membrane diastolic depolarization and slowing of repolarization than did nifedipine. Verapamil also produced a more marked decrease in +dV/dtmax. In ion flux studies, it was demonstrated that verapamil produced a significant inhibition of 24Na influx, relative to control, whereas nifedipine did not. Verapamil also produced a slight decrease in 42K efflux, of borderline significance. These findings support previous results which indicate there are differences in the mechanisms of action of these Ca2+-channel blocking drugs.
为了研究硝苯地平和维拉帕米作用机制的可能差异，在培养的鸡胚心室细胞暴露于这些药物期间，同步记录膜电位和细胞运动。维拉帕米和硝苯地平均产生快速的负性肌力作用和兴奋 - 收缩偶联延迟，这可能与两种药物通过慢钙通道抑制Ca2+内流的能力有关，从而降低[Ca2+]i瞬变。然而，对于同等程度的负性肌力作用，维拉帕米比硝苯地平产生相对更多的膜舒张期去极化和复极化减慢。维拉帕米还使 +dV/dtmax 有更明显的降低。在离子通量研究中，结果表明，与对照组相比，维拉帕米对24Na内流有显著抑制作用，而硝苯地平则无此作用。维拉帕米还使42K外流略有减少，具有临界显著性。这些发现支持了先前的结果，即表明这些钙通道阻滞剂的作用机制存在差异。
