A capacitative calcium current in cultured skeletal muscle cells is mediated by the calcium-specific leak channel and inhibited by dihydropyridine compounds

被引:81
作者
Hopf, FW [1 ]
Reddy, P [1 ]
Hong, J [1 ]
Steinhard, RA [1 ]
机构
[1] UNIV CALIF BERKELEY,DEPT MOL & CELL BIOL,BERKELEY,CA 94720
关键词
D O I
10.1074/jbc.271.37.22358
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Calcium stores from cultured skeletal muscle cells were depleted using cyclopiazonic acid (CPA), a reversible inhibitor of Ca2+-ATPases at the sarcoplasmic reticulum. Store depletion led to activation of the calcium-specific leak channel, as assayed using single-channel patch clamp analysis and rates of manganese influx and quenching of fura-2 fluorescence. Two novel dihydropyridine compounds inhibited this single-channel leak channel activity, the resting and depletion-induced manganese influx, and refilling of the CPA-depleted intracellular calcium store. These compounds represent the first antagonists for a calcium leak channel and for a channel that mediates a capacitative current. The development of the skeletal muscle capacitative current was inhibited by genistein, a tyrosine kinase inhibitor, but was not affected by okadaic acid, a phosphatase inhibitor, or econazole. Thus, the capacitative current in cultured skeletal muscle cells was mediated by the calcium leak channel and was inhibited by pharmacological antagonists and may provide a model system for uncovering the complete set of signals leading from store depletion to channel activation.
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页码:22358 / 22367
页数:10
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