Ryanodine Receptor Luminal Ca2+ Regulation: Swapping Calsequestrin and Channel Isoforms
AUTOR(ES)
Qin, Jia
FONTE
The Biophysical Society
RESUMO
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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2756356Documentos Relacionados
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