Ferry D R, Goll A, Glossmann H
EMBO J. 1983;2(10):1729-32. doi: 10.1002/j.1460-2075.1983.tb01649.x.
Radiation inactivation was employed to measure the molecular size of calcium channels in guinea-pig skeletal muscle membranes, labelled by the potent 1,4-dihydropyridine calcium antagonist [3H]nimodipine. The molecular size was decreased when the membranes were preincubated and assayed with d-cis-diltiazem, a calcium channel blocker, which is structurally unrelated to the 1,4-dihydropyridines. d-cis-Diltiazem, which is a positive heterotropic regulator of 1,4-dihydropyridine calcium channel binding in vitro, reduced the molecular size from 178 000 to 111 500. 1-cis-Diltiazem, the diastereoisomer, which is devoid of calcium antagonistic action, did not decrease the molecular size of the 1,4-dihydropyridine binding site. Neither diastereoisomer affected the molecular size of the membrane-bound acetyl-cholinesterase, indicating that a stereospecific interaction with the calcium channel structure is the basis for these observations. It is concluded that this decrease in size is indicative of the oligomeric nature of the calcium channel and that calcium channel blockers, acting via different, but interacting drug receptor sites, induce different conformations of the channel structure, resulting in altered conductivity for ions.
采用辐射失活法测定豚鼠骨骼肌膜中钙通道的分子大小，该膜用强效1,4 - 二氢吡啶类钙拮抗剂[3H]尼莫地平进行标记。当膜用钙通道阻滞剂d - 顺式地尔硫䓬预孵育并进行测定时，分子大小减小，d - 顺式地尔硫䓬与1,4 - 二氢吡啶类在结构上无关。d - 顺式地尔硫䓬在体外是1,4 - 二氢吡啶类钙通道结合的正性异向调节剂，它使分子大小从178000减小到111500。无钙拮抗作用的非对映异构体1 - 顺式地尔硫䓬并未减小1,4 - 二氢吡啶结合位点的分子大小。两种非对映异构体均未影响膜结合乙酰胆碱酯酶的分子大小，表明与钙通道结构的立体特异性相互作用是这些观察结果的基础。得出的结论是，这种大小的减小表明钙通道具有寡聚性质，并且钙通道阻滞剂通过不同但相互作用的药物受体位点起作用，诱导通道结构的不同构象，从而导致离子电导率改变。
