Calcium-induced calcium release (CICR) describes a biological process whereby
calcium is able to activate calcium release from intracellular Ca2+ stores (e.g.,
endoplasmic reticulum or
sarcoplasmic reticulum). Although CICR was first proposed for
skeletal muscle in the 1970s,
[1] it is now known that CICR is unlikely to be its primary mechanism for activating
SR calcium release. Instead, CICR is thought to be crucial for
excitation-contraction coupling in
cardiac muscle[2] and it is now obvious that CICR is a widely occurring cellular signaling process present even in many non-muscle cells, e.g. in the insulin-secreting pancreatic beta cells
[3] and many other cells. Since CICR is a positive-feedback system, it has been of great interest to elucidate the mechanism(s) responsible for its termination.