Insulin increases near-membrane but not global Ca2+ in isolated skeletal muscle

被引:56
作者
Bruton, JD
Katz, A
Westerblad, H [1 ]
机构
[1] Karolinska Inst, Dept Physiol & Pharmacol, S-17177 Stockholm, Sweden
[2] Karolinska Inst, Dept Surg Sci, S-17177 Stockholm, Sweden
关键词
D O I
10.1073/pnas.96.6.3281
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
It has long been debated whether changes in Ca2+ are involved in insulin-stimulated glucose uptake in skeletal muscle. We have now investigated the effect of insulin on the global free myoplasmic Ca2+ concentration and the near-membrane free Ca2+ concentration ([Ca2+](mem)) in intact, single skeletal muscle fibers from mice by using fluorescent Ca2+ indicators. Insulin has no effect on the global free myoplasmic Ca2+ concentration. However, insulin increases [Ca2+](mem) by approximate to 70% and the half-maximal increase in [Ca2+](mem) occurs at an insulin concentration of 110 microunits per mi. The increase in [Ca2+](mem) by insulin persists when sarcoplasmic reticulum Ca2+ release is inhibited but is lost by perfusing the fiber with a low Ca2+ medium or by addition of L-type Ca2+ channel inhibitors. Thus, insulin appears to stimulate Ca2+ entry into muscle cells via L-type Ca2+ channels, Wortmannin, which inhibits insulin-mediated activation of glucose transport in isolated skeletal muscle, also inhibits the insulin-mediated increase in [Ca2+](mem). These data demonstrate a new facet of insulin signaling and indicate that insulin-mediated increases in [Ca2+](mem) in skeletal muscle may underlie important actions of the hormone.
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页码:3281 / 3286
页数:6
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