Spontaneous calcium release from the sarcoplasmic reticulum in myocardial cells: mechanisms and consequences

Under certain conditions of Ca²⁺ loading, cardiac myocytes, both isolated and in intact tissue, exhibit spontaneous, oscillatory Ca²⁺ transients due to Ca²⁺ release from the sarcoplasmic reticulum. These transients are not triggered by depolarization of the sarcolemma, though they themselves can generate depolarizing currents which can reach threshold to trigger an action potential. Spontaneous Ca²⁺ release occurs locally in a subcellular region and, once initiated, can propagate through the cell with a velocity of roughly 100 μm/s. Locally, the cytosolic Ca²⁺ concentration during spontaneous release is probably comparable to that during an electrically excited twitch. The mechanisms of initiation and propagation of spontaneous Ca²⁺ release are uncertain, but are probably closely related to the Ca²⁺-induced Ca²⁺ release which plays a role in normal excitation-contraction coupling. Spontaneous and triggered Ca²⁺ release appear to compete for a common pool of releasable sarcoplasmic reticulum Ca²⁺, with the result that spontaneous Ca²⁺ release imposes a beat-rate-dependent limit on the inotropic effect of interventions which increase intracellular Ca²⁺. Mathematical modeling of this effect shows that it can also explain increased diastolic tone, the development of aftercontractions and oscillatory restitution of contractility in states of 'Ca²⁺ overload'. Spontaneous Ca²⁺ release is a cause of arrhythmias, and may well play a role in some cases of systolic and diastolic myocardial dysfunction.