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—The control of intracellular calcium is central to regulation of contractile force in cardiac muscle. This review illustrates how analysis of the control of calcium requires an integrated approach in which several systems are considered. Thus, the calcium content of the sarcoplasmic reticulum (SR) is a major determinant of the amount of Ca²⁺ released from the SR and the amplitude of the Ca²⁺ transient. The amplitude of the transient, in turn, controls Ca²⁺ fluxes across the sarcolemma and thence SR content. This control of SR content influences the response to maneuvers that modify, for example, the properties of the SR Ca²⁺ release channel or ryanodine receptor. Specifically, modulation of the open probability of the ryanodine receptor produces only transient effects on the Ca²⁺ transient as a result of changes of SR content. These interactions between various Ca²⁺ fluxes are modified by the Ca²⁺ buffering …