The majority of contractile calcium in cardiac muscle is released from stores in the
sarcoplasmic reticulum (SR), by a process of calcium-induced calcium release (CICR)
through ryanodine receptors. Because CICR is intrinsically self-reinforcing, the stability of
and graded regulation of cardiac EC coupling appear paradoxical. It is now well established
that this gradation results from the stochastic recruitment of varying numbers of elementary
local release events, which may themselves be regenerative, and which can be directly …