Calcium-induced calcium release

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, 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 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 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.

Excitation-contraction coupling in myocardium relies on sarcolemma depolarization & subsequent Ca²⁺ entry to trigger Ca²⁺ release from the sarcoplasmic reticulum. When an action potential depolarizes the cell membrane, voltage-gated Ca²⁺ channels (e.g., L-type calcium channels) are activated. CICR occurs when the resulting Ca²⁺ influx activates ryanodine receptors on the SR membrane, which causes more Ca²⁺ to be released into the cytosol. In cardiac muscle, the result of CICR is observed as a spatio-temporally restricted Ca²⁺ spark. The result of CICR across the cell causes the significant increase in cytosolic Ca²⁺ that is important in activating muscle contraction.

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