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,[1] it is now known that CICR is unlikely to be the 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.

Examples in biology

Excitation-contraction coupling

Excitation-contraction coupling in myocardium relies on sarcolemma depolarization and 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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References
  1. Endo, M (1977). "Calcium release from the sarcoplasmic reticulum". Physiological Reviews. 57 (1): 71–108. doi:10.1152/physrev.1977.57.1.71. PMID 13441.
  2. Fabiato, A. (1983). "Calcium-induced calcium release from the cardiac sarcoplasmic reticulum". American Journal of Physiology. 245 (1): C1-14. doi:10.1152/ajpcell.1983.245.1.C1. PMID 6346892.
  3. Islam, Md.Shahidul; Rorsman, Patrik; Berggren, Per-Olof (1992). "Ca2+-induced Ca2+ release in insulin-secreting cells". FEBS Letters. 296 (3): 287–91. doi:10.1016/0014-5793(92)80306-2. PMID 1537406.
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