Calcium-induced calcium release

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Calcium-induced calcium release (CICR) is a process whereby calcium can trigger release of further calcium from the muscle sarcoplasmic reticulum. Originally proposed for skeletal muscle in the 1970s, subsequent research has revealed that it is even more pronounced in the cardiac muscle. 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.

The muscle cell membrane (sarcolemma) contains many ion receptors. One of which is the voltage-gated ion channel DHPR (Dihydropyridine receptor) which allows the entry of calcium ions into the cytosol. The sarcoplasmic reticulum (myocyte version of the endoplasmic reticulum) stores calcium ions. On the sarcoplasmic reticulum there is a receptor called the ryanodine receptor, which is sensitive to cytosolic calcium ions. The ryanodine receptor(RYR) is a calcium release channel which releases the sarcoplasmic reticulum's(SR) calcium stores. The increase in intracellular Ca²⁺ ions induces the RYR to release even more Ca²⁺ from the SR.

The purpose of this mechanism is to release a very small, yet significant, proportion of calcium into the muscle's cytosol. The calcium ions eventually bind to an accessory protein found on the actin filament, which stimulates muscle contraction.

Ca²⁺ ions are a key component to muscle contraction.

CICR in Excitation-Contraction (EC) Coupling

The mechanism that couples excitation - an action potential in the plasma membrane of the muscle cell - and contraction of heart muscle is an increase in the cell's cytosolic calcium concentration. This calcium combines with the regulator protein, troponin, initiating cross-bridge formation between actin and myosin.