The mechanical contraction of cardiac muscle is triggered by membrane depolarization through a process known as calcium-induced calcium-release (CICR). The structural basis of CICR is exquisite in its detail. At thousands of distinct locations throughout the myocyte, the junctional sarcoplasmic reticulum (JSR) membrane approaches to within -12 nm of the t-tubule membrane to form structures known as dyads. Dyads consist of a handful of L-type calcium (Ca~(2+)) channels (LCCs) in the t-tubule membrane, a larger number of ryanodine-sensitive Ca~(2+)-gated Ca~(2+)-release channels (RyR2s) in the closely apposed JSR membrane, regulatory proteins that modify LCC and RyR2 function, and the fluid volume that separates them. Membrane depolarization leads to openings of LCCs, flux of Ca~(2+) into the dyadic space, Ca~(2+) binding to and opening of RyR2s, and release of Ca~(2+) from the JSR into the dyadic space. This Ca~(2+) then diffuses out of the dyad and binds to the mechanical machinery of the cell. The sum of these Ca~(2+) release events drives contraction of heart muscle.
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