Kojima M, Sperelakis N
Eur J Pharmacol. 1983 Oct 14;94(1-2):9-18. doi: 10.1016/0014-2999(83)90436-3.
Young (3-day-old) embryonic chick hearts have slowly rising action potentials (APs) dependent on slow Na+ channels, and these slow APs are blocked by verapamil, but not by Mn2+ (1 mM). In contrast, old embryonic hearts possess slow Ca2+-Na+ channels which can be blocked by both verapamil and Mn2+. In the present experiments, we compared the effects of a number of Ca antagonistic drugs on the spontaneous APs recorded from intact 3-day-old embryonic chick hearts (ventricles). At 10(-5) M, verapamil, D-600, and nifedipine abolished the spontaneous APs (3 X 10(-6) M produced some depression of Vmax). Electrical stimulation did not elicit APs, and long-duration hyperpolarizing pulses (applied because the maximum diastolic potential was moderately decreased) did not allow APs to be elicited by stimulation. This blockade was not reversed by elevation of [Ca]0 from 0.6 mM (control concentration used to reduce contractions) to 3.6 mM or 5.4 mM. However, lowering of [Na]0 from 137 mM to 68.5 mM facilitated the blockade. Washout of the drugs for 30 min produced nearly complete recovery. In contrast to the effects of verapamil, D-600, and nifedipine, 10(-5) M diltiazem, bepridil, and mesudipine had little or no depressant effect on Vmax; the same was true for 1 mM Mn2+. These results indicate that verapamil, D-600, and nifedipine are blockers of slow Na+ channels (as well as of slow Ca2+-Na+ channels), whereas diltiazem, bepridil and mesudipine do not block slow Na+ channels. Therefore, the Ca antagonistic drugs vary in their ability to block slow Na+ channels.
3日龄的幼龄胚胎鸡心脏具有依赖于慢钠通道的缓慢上升动作电位（APs），这些慢动作电位可被维拉帕米阻断，但不受1 mM Mn2+的影响。相比之下，老龄胚胎心脏具有慢钙-钠通道，可被维拉帕米和Mn2+阻断。在本实验中，我们比较了多种钙拮抗药物对完整的3日龄胚胎鸡心脏（心室）记录的自发动作电位的影响。在10(-5) M时，维拉帕米、D-600和硝苯地平使自发动作电位消失（3×10(-6) M对最大上升速率有一定程度的降低）。电刺激不能诱发动作电位，长时间的超极化脉冲（由于最大舒张电位适度降低而施加）也不能使刺激诱发动作电位。将细胞外钙浓度[Ca]0从0.6 mM（用于减少收缩的对照浓度）提高到3.6 mM或5.4 mM并不能逆转这种阻断作用。然而，将细胞外钠浓度[Na]0从137 mM降低到68.5 mM则促进了这种阻断作用。药物洗脱30分钟后几乎完全恢复。与维拉帕米、D-600和硝苯地平的作用相反，10(-5) M地尔硫卓、苄普地尔和甲硫地平对最大上升速率几乎没有或没有抑制作用；1 mM Mn2+也是如此。这些结果表明，维拉帕米、D-600和硝苯地平是慢钠通道（以及慢钙-钠通道）的阻滞剂，而地尔硫卓、苄普地尔和甲硫地平不阻断慢钠通道。因此，钙拮抗药物在阻断慢钠通道的能力上存在差异。
