An intelligent sarco-endoplasmic reticulum Ca2+ store: release and leak channels have differential access to a
Agustin Guerrero-Hernandez1, Adan Dagnino-Acosta, Alexei Verkhratsky
1Department of Biochemistry, Cinvestav-IPN, México City, DF, Mexico. aguerrero@cinvestav.mx
Abstract:
Simultaneous recording of cytosolic and sarco-endoplasmic reticulum (SR/ER) luminal free calcium concentrations ([Ca(2+)](i) and [Ca(2+)](L), respectively) supports the notion that release channels (RyRs and IP(3)Rs) use a concealed Ca(2+) source, likely to be associated with intra-SR/ER Ca(2+) binding proteins, whereas SR/ER Ca(2+) leak channels can only access free luminal Ca(2+). We hypothesize that Ca(2+) is trapped by oligomers of luminal Ca(2+)-binding proteins and that the opening of release channels induces the rapid liberation of this "concealed" Ca(2+) source associated with intra-ER Ca(2+) buffers. Our hypothesis may also clarify why SERCA pumps potentiate Ca(2+) release and explain quantal characteristics and refractory states of Ca(2+) release process.
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