Ryanodine Receptor Luminal Ca2+ Regulation: Swapping Calsequestrin and Channel Isoforms
Ryanodine Receptor Luminal Ca2+ Regulation: Swapping Calsequestrin and Channel Isoforms
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DOI：
10.1016/j.bpj.2009.07.030
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发表时间：
2009-10-07
影响因子：
3.4
通讯作者：
Fill, Michael
中科院分区：
文献类型：
--
作者：
Qin, Jia;Valle, Giorgia;Fill, Michael
肌浆网(SR)钙释放是由一个多蛋白复合体介导的，该复合体包括Ryanodine受体(RyR)钙通道和肌浆网内钙缓冲蛋白Calequestrin(CSQ)。除了缓冲作用外，CSQ还被认为调节RyR通道功能。在这里，我们探讨了依赖CSQ的钙离子对骨骼(RyR1)和心脏(RyR2)通道的调节。将骨骼(CSQ1)或心脏(CSQ2)钙调素系统地添加到单个RyR1或RyR2通道的管腔侧。四种RyR/CSQ亚型对的开放概率(PO)在生理相关范围(0.05-1 mMCa~(2+))上的管腔钙依赖性被定义。我们发现当两种CSQ亚型中的任何一种存在时，单个RyR2通道的腔内钙敏感性是显著的。相反，在任何一种CSQ亚型存在下，都没有检测到单个RyR1通道对钙的显著敏感性。我们的结论是，依赖CSQ的单个RyR2通道的管腔钙调节缺乏CSQ异构体的特异性，而骨骼肌中依赖CSQ的管腔钙调节可能在调节RyR1通道的活动中起到相对较小的作用(如果有的话)，这表明CSQ1在该组织中的主要作用是作为SR内的钙缓冲。
Sarcoplasmic reticulum (SR) Ca2+ release in striated muscle is mediated by a multiprotein complex that includes the ryanodine receptor (RyR) Ca2+ channel and the intra-SR Ca2+ buffering protein calsequestrin (CSQ). Besides its buffering role, CSQ is thought to regulate RyR channel function. Here, CSQ-dependent luminal Ca2+ regulation of skeletal (RyR1) and cardiac (RyR2) channels is explored. Skeletal (CSQ1) or cardiac (CSQ2) calsequestrin were systematically added to the luminal side of single RyR1 or RyR2 channels. The luminal Ca2+ dependence of open probability (PO) over the physiologically relevant range (0.05-1 mM Ca2+) was defined for each of the four RyR/CSQ isoform pairings. We found that the luminal Ca2+ sensitivity of single RyR2 channels was substantial when either CSQ isoform was present. In contrast, no significant luminal Ca2+ sensitivity of single RyR1 channels was detected in the presence of either CSQ isoform. We conclude that CSQ-dependent luminal Ca2+ regulation of single RyR2 channels lacks CSQ isoform specificity, and that CSQ-dependent luminal Ca2+ regulation in skeletal muscle likely plays a relatively minor (if any) role in regulating the RyR1 channel activity, indicating that the chief role of CSQ1 in this tissue is as an intra-SR Ca2+ buffer.