Zühlke R D, Bouron A, Soldatov N M, Reuter H
Department of Pharmacology, University of Bern, Switzerland.
FEBS Lett. 1998 May 8;427(2):220-4. doi: 10.1016/s0014-5793(98)00425-6.
L-type Ca2+ channels are important targets for drugs, such as dihydropyridines (DHPs), in the treatment of cardiovascular diseases. Channel expression is regulated by alternative splicing. It has been suggested that in the cardiovascular system tissue-specific expression of different L-type Ca2+ channel splice variants may underlie the observed differences in sensitivities to channel block by DHPs. We investigated the sensitivity of Ca2+ channel splice variants derived from the human alpha1C gene to the DHP isradipine. Among seven alpha1C channels we observed up to 10-fold differences in IC50 values for isradipine, as well as changes in the voltage dependence of DHP action.
L型钙通道是治疗心血管疾病药物（如二氢吡啶类药物）的重要靶点。通道表达受可变剪接调控。有人提出，在心血管系统中，不同L型钙通道剪接变体的组织特异性表达可能是观察到的对二氢吡啶类药物通道阻滞敏感性差异的基础。我们研究了源自人类α1C基因的钙通道剪接变体对二氢吡啶类药物伊拉地平的敏感性。在7种α1C通道中，我们观察到伊拉地平的半数抑制浓度（IC50）值存在高达10倍的差异，以及二氢吡啶类药物作用电压依赖性的变化。
