T he heart, beating constantly over the course of the human lifetime, operates continuously through the process of excitation-contraction coupling. Initiated by a depolarizing influx of Na, a small Ca 2ϩ flux across the sarcolemma causes a large release of Ca 2ϩ from the sarcoplasmic reticulum (SR). Release of this Ca 2ϩ takes place via the ryanodine receptor (RyR), a Ca 2ϩ channel within the SR membrane which is gated by cytoplasmic Ca 2ϩ ([Ca 2ϩ ] i ). 1 This gating takes place to a small but

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... significant extent even at the relatively low [Ca 2ϩ ] i found during diastole within the myocyte (SR Ca 2ϩ leak). Among the striking features of this SR Ca 2ϩ release is its steep nonlinear dependence on the total concentration of Ca 2ϩ found in the lumen of the SR ([Ca 2ϩ ] SRT ). The degree of release at diastolic [Ca 2ϩ ] i is very low when the [Ca 2ϩ ] SRT is approximately 50% of the level usually found in an isolated cardiac myocyte. 2 However, it increases dramatically as [Ca 2ϩ ] SRT increases toward its normal level.