FUNCTION OF A TRUNCATED DIHYDROPYRIDINE RECEPTOR AS BOTH VOLTAGE SENSOR AND CALCIUM-CHANNEL

FUNCTION OF A TRUNCATED DIHYDROPYRIDINE RECEPTOR AS BOTH VOLTAGE SENSOR AND CALCIUM-CHANNEL
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DOI:
10.1038/360169a0
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发表时间:
1992-11-12
期刊:
影响因子:
64.8
通讯作者:
TANABE, T
TANABE, T
中科院分区:
综合性期刊1区
文献类型:
--
作者:
BEAM, KG;ADAMS, BA;TANABE, T

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骨骼肌二氢吡啶(DHP)受体具有双重功能,作为兴奋-收缩偶联的电压传感器和L型钙通道1 -3。生化分析表明,骨骼肌中存在两种形式的DHP受体多肽,一种是作为次要物质存在的全长翻译产物,另一种是具有截短羧基末端的更丰富形式4 -6。基于这些和其他观察结果7,有人提出8,在骨骼肌中,只有全长DHP受体可以作为钙通道,而截短的形式只能作为兴奋-收缩耦合的电压传感器。为了解决这个问题,我们现在已经构建了一个互补的DNA(pC6 DELTA 1)编码的蛋白质对应于截短的DHP受体在骨骼肌。pC6 DELTA 1在发育不良的肌管中的表达完全恢复了兴奋-收缩偶联和钙电流,这与单一类别的DHP受体执行两种功能的想法一致。
THE skeletal muscle dihydropyridine (DHP) receptor serves dual functions, as a voltage sensor for excitation-contraction coupling and as an L-type calcium channel1-3. Biochemical analysis indicates the presence of two forms of the DHP receptor polypeptide in skeletal muscle, a full-length translation product present as a minor species and a much more abundant form that has a truncated carboxy-terminus4-6. On the basis of these and other observations7, it has been proposed8 that, in skeletal muscle, only the full-length DHP receptor can function as a calcium channel and that the truncated form can only function as a voltage sensor for excitation-contraction coupling. To resolve this issue, we have now constructed a complementary DNA (pC6DELTA1) encoding a protein corresponding to the truncated DHP receptor in skeletal muscle. Expression of pC6DELTA1 in dysgenic myotubes fully restores both excitation-contraction coupling and calcium current, consistent with the idea that a single class of DHP receptors performs both functions.