Schwartz L M, McCleskey E W, Almers W
Nature. 1985;314(6013):747-51. doi: 10.1038/314747a0.
1,4-Dihydropyridines are a new class of compounds believed to bind specifically and with high affinity to voltage-dependent calcium channels. They may be the first example of a ligand of use in the extraction and purification of the Ca channel. Although Ca channels and dihydropyridine receptors are found in many tissues, the richest and most convenient source is skeletal muscle. Functionally, 1,4-dihydropyridines such as nifedipine and nitrendipine block Ca channels; this effect is believed to form the basis for their clinical importance as Ca antagonists in relaxing vascular smooth muscle. But where currents through Ca channels can be measured directly, the block has required 100-1,000 times higher concentrations of dihydropyridine than necessary for the saturation of dihydropyridine binding sites. This discrepancy has remained unresolved because the study of pharmacological effects on Ca channels has required intact cells, while it has been difficult to investigate binding in other than cell-free preparations. Here we describe a method for measuring dihydropyridine binding to intact skeletal muscle and we compare our results with voltage-clamp measurements of Ca-channel block. We conclude that less than a few per cent of the binding sites in skeletal muscle represent functional Ca channels, contrary to general belief.
1,4 - 二氢吡啶是一类新的化合物，据信它们能特异性且高亲和力地结合电压依赖性钙通道。它们可能是用于钙通道提取和纯化的配体的首个实例。尽管钙通道和二氢吡啶受体存在于许多组织中，但最丰富且最便利的来源是骨骼肌。在功能上，硝苯地平和尼群地平等1,4 - 二氢吡啶可阻断钙通道；这种效应被认为是它们作为钙拮抗剂在舒张血管平滑肌方面具有临床重要性的基础。但是在能够直接测量通过钙通道的电流的情况下，产生阻断所需的二氢吡啶浓度比使二氢吡啶结合位点饱和所需的浓度高100 - 1000倍。这一差异一直未得到解决，因为对钙通道的药理作用研究需要完整细胞，而在无细胞制剂以外的体系中研究结合情况一直很困难。在此我们描述一种测量二氢吡啶与完整骨骼肌结合的方法，并将我们的结果与钙通道阻断的电压钳测量结果进行比较。我们得出结论，与普遍看法相反，骨骼肌中不到百分之几的结合位点代表功能性钙通道。
