Wegener J W, Nawrath H
Pharmakologisches Institut der Universität Mainz, Germany.
Eur J Pharmacol. 1995 Dec 4;287(1):89-92. doi: 10.1016/0014-2999(95)00626-1.
The effect of verapamil on L-type Ca2+ current (ICa) was compared at external pH 7.4 and 8.5 in rat ventricular myocytes. Alkalinisation increases the fraction of uncharged molecules of verapamil (pK 8.75) and thereby facilitates membrane permeation of the drug. Verapamil (1 microM) reduced the amplitude of ICa (ICa(peak)) by 36 +/- 4% at pH 7.4 and by 40 +/- 6% at pH 8.5, whereas alkalinisation from pH 7.4 to 8.5, without drug, increased ICa(peak) by 12 +/- 3%. It is suggested that the efficiency of verapamil is not influenced by the amount of protonation or membrane permeation.
在大鼠心室肌细胞中，比较了维拉帕米在细胞外pH值为7.4和8.5时对L型钙电流（ICa）的作用。碱化会增加维拉帕米（pK 8.75）不带电荷分子的比例，从而促进药物的膜渗透。维拉帕米（1微摩尔）在pH值为7.4时使ICa（ICa峰值）的幅度降低36±4%，在pH值为8.5时降低40±6%，而在无药物情况下将pH值从7.4碱化至8.5会使ICa峰值增加12±3%。提示维拉帕米的作用效率不受质子化程度或膜渗透的影响。
