title: Calcium-induced calcium release
text: # Calcium-induced calcium release
  
  Calcium-induced calcium release (CICR) describes a biological process whereby calcium is able to activate calcium release from intracellular $Ca^{2+}$ 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 the primary mechanism for activating SR calcium release. Instead, CICR is thought to be crucial for excitation-contraction coupling in cardiac muscle. It is now obvious that CICR is a widely occurring cellular signaling process present even in many non-muscle cells, such as in the insulin-secreting pancreatic beta cells, epithelium, 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 $Ca^{2+}$ entry to trigger $Ca^{2+}$ release from the sarcoplasmic reticulum. When an action potential depolarizes the cell membrane, voltage-gated $Ca^{2+}$ channels (e.g., L-type calcium channels) are activated. CICR occurs when the resulting $Ca^{2+}$ influx activates ryanodine receptors on the SR membrane, which causes more $Ca^{2+}$ to be released into the cytosol. In cardiac muscle, the result of CICR is observed as a spatio-temporally restricted $Ca^{2+}$ spark. The result of CICR across the cell causes the significant increase in cytosolic $Ca^{2+}$ that is important in activating muscle contraction.
  
  