An intelligent sarco-endoplasmic reticulum Ca2+ store: Release and leak channels have differential access to a concealed Ca2+ pool

Simultaneous recording of cytosolic and sarco-endoplasmic reticulum (SR/ER) luminal free calcium concentrations ([Ca2+]i and [Ca2+]L, respectively) supports the notion that release channels (RyRs and IP3Rs) use a concealed Ca2+ source, likely to be associated with intra-SR/ER Ca2+ binding proteins, whereas SR/ER Ca2+ leak channels can only access free luminal Ca2+. We hypothesize that Ca2+ is trapped by oligomers of luminal Ca2+-binding proteins and that the opening of release channels induces the rapid liberation of this “concealed” Ca2+ source associated with intra-ER Ca2+ buffers. Our hypothesis may also clarify why SERCA pumps potentiate Ca2+ release and explain quantal characteristics and refractory states of Ca2+ release process.