Local control in cardiac E-C coupling

► The background to the development of local control (LC) theories for cardiac excitation-contraction coupling is described. ► LC theories solve the problem of uncontrolled cell-wide regeneration during calcium-induced calcium release (CICR). ► Evidence for LC of CICR includes cytoplasmic Ca sparks and local sarcoplasmic reticulum (SR) calcium depletions ('blinks'). ► Termination of local CICR remains unclear and key processes contributing to stochastic attrition are discussed. ► Ryanodine receptor gating modulates mean SR Ca levels which may regulate other cellular functions beyond contractility.