Varadi G, Lory P, Schultz D, Varadi M, Schwartz A
Department of Pharmacology and Cell Biophysics, University of Cincinnati, Ohio 45267-0575.
Nature. 1991 Jul 11;352(6331):159-62. doi: 10.1038/352159a0.
The L-type voltage-dependent calcium channel is an important link in excitation-contraction coupling of muscle cells (reviewed in refs 2 and 3). The channel has two functional characteristics: calcium permeation and receptor sites for calcium antagonists. In skeletal muscle the channel is a complex of five subunits, alpha 1, alpha 2, beta, gamma and delta. Complementary DNAs to these subunits have been cloned and their amino-acid sequences deduced. The skeletal muscle alpha 1 subunit cDNA expressed in L cells manifests as specific calcium-ion permeation, as well as sensitivity to the three classes of organic calcium-channel blockers. We report here that coexpression of the alpha 1 subunit with other subunits results in significant changes in dihydropyridine binding and gating properties. The available number of drug receptor sites increases 10-fold with an alpha 1 beta combination, whereas the affinity of the dihydropyridine binding site remains unchanged. Also, the presence of the beta subunit accelerates activation and inactivation kinetics of the calcium-channel current.
L型电压依赖性钙通道是肌肉细胞兴奋-收缩偶联中的一个重要环节（参考文献2和3中有综述）。该通道具有两个功能特性：钙通透性和钙拮抗剂受体位点。在骨骼肌中，该通道是由α1、α2、β、γ和δ五个亚基组成的复合体。已克隆出这些亚基的互补DNA，并推导了它们的氨基酸序列。在L细胞中表达的骨骼肌α1亚基cDNA表现出特定的钙离子通透性，以及对三类有机钙通道阻滞剂的敏感性。我们在此报告，α1亚基与其他亚基的共表达会导致二氢吡啶结合和门控特性发生显著变化。α1β组合使药物受体位点的可用数量增加10倍，而二氢吡啶结合位点的亲和力保持不变。此外，β亚基的存在加速了钙通道电流的激活和失活动力学。
