Rapid calcium release from cardiac sarcoplasmic reticulum vesicles is dependent on Ca2+ and is modulated by Mg2+, adenine nucleotide, and calmodulin.
Rapid calcium release from cardiac sarcoplasmic reticulum vesicles is dependent on Ca2+ and is modulated by Mg2+, adenine nucleotide, and calmodulin.
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DOI：
10.1016/s0021-9258(18)61469-3
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发表时间：
1987-03
期刊：
影响因子：
--
通讯作者：
G. Meissner;Julia;Henderson
中科院分区：
文献类型：
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作者：
G. Meissner;Julia;Henderson
已发现犬心肌肌浆网囊泡的亚群含有“Ca 2+释放通道”，其以足够快的速率介导囊泡内Ca 2+储存的释放，以促进心肌中的兴奋-收缩偶联。通过Millipore过滤和使用快速淬灭装置，使用两种Ca 2+通道抑制剂Mg 2+和钌红，测定被动和主动负载囊泡的45 Ca 2+释放行为。在pH7.0和5-20 μ M外Ca ~（2+）时，心囊泡在20 ms内释放一半的~（45）Ca ~（2+）。钙调素降低钙离子诱导的钙离子释放速率3-6倍的反应，似乎并不涉及钙调素依赖性蛋白激酶。在不同的实验条件下，ATP或不可水解的ATP类似物，腺苷5 '-（β，γ-亚甲基）三磷酸（AMP-PCP）和咖啡因刺激45 Ca 2+释放2-500倍。最大释放速率（t1/2 = 10 ms），观察到在培养基中含有10 μ M的Ca 2+和5 mM AMP-PCP或10 mM咖啡因。在8 mM Mg 2+和5 mM AMP-PCP存在下，需要增加的外部Ca 2+浓度（大于或等于1 mM）以优化45 Ca 2+流出速率。这些结果表明，心肌肌浆网含有一个配体门控的Ca ~（2+）通道，该通道被Ca ~（2+）、腺嘌呤核苷酸和咖啡因激活，并被Mg ~（2+）、H ~+和钙调蛋白抑制。
A subpopulation of canine cardiac sarcoplasmic reticulum vesicles has been found to contain a “Ca2+ release channel” which mediates the release of intravesicular Ca2+ stores with rates sufficiently rapid to contribute to excitation-contraction coupling in cardiac muscle. 45Ca2+ release behavior of passively and actively loaded vesicles was determined by Millipore filtration and with the use of a rapid quench apparatus using the two Ca2+ channel inhibitors, Mg2+ and ruthenium red. At pH 7.0 and 5-20 microM external Ca2+, cardiac vesicles released half of their 45Ca2+ stores within 20 ms. Ca2+-induced Ca2+ release was inhibited by raising and lowering external Ca2+ concentration, by the addition of Mg2+, and by decreasing the pH. Calmodulin reduced the Ca2+-induced Ca2+ release rate 3-6-fold in a reaction that did not appear to involve a calmodulin-dependent protein kinase. Under various experimental conditions, ATP or the nonhydrolyzable ATP analog, adenosine 5'-(beta, gamma-methylene)triphosphate (AMP-PCP), and caffeine stimulated 45Ca2+ release 2-500-fold. Maximal release rates (t1/2 = 10 ms) were observed in media containing 10 microM Ca2+ and 5 mM AMP-PCP or 10 mM caffeine. An increased external Ca2+ concentration (greater than or equal to 1 mM) was required to optimize the 45Ca2+ efflux rate in the presence of 8 mM Mg2+ and 5 mM AMP-PCP. These results suggest that cardiac sarcoplasmic reticulum contains a ligand-gated Ca2+ channel which is activated by Ca2+, adenine nucleotide, and caffeine, and inhibited by Mg2+, H+, and calmodulin.