Cardiac excitation-contraction coupling (ECC) is, in essence, a communication process between sarcolemmal voltage-dependent L-type calcium channels (LCCs) and ryanodine receptors (RyRs) of sarcoplasmic reticulum (SR) by the mechanism of calcium-induced calcium release (CICR). Recent advances displayed more information about the microscopic signaling between LCCs and RyRs. In calcium release couplons, the calcium influx through the opening of LCCs by membrane depolarization forms calcium sparklets locally which then act on the adjacent SR RyRs. Stochastic activation of RyRs discharges calcium sparks from different calcium couplons, which summate into global calcium transients. Therefore, ignition of calcium sparks by calcium sparklets constitutes the elementary events in ECC. This review focuses on the intermolecular signaling between LCCs and RyRs, to describe the microscopic view of CICR and ECC.

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