A mathematical model of Ca2+-release and Ca2+ balance during systole in rat ventricular myocytes

It is well-established that mammalian cardiac excitation-contraction coupling is mediated by Ca²⁺-induced Ca²⁺ release (CICR). We have developed a lumped equivalent component model of the I_Ca,L trigger Ca²⁺ release process that includes component models of Ca²⁺ diffusion in the local representative dyadic cleft space; Ca²⁺ release from local representative release complex on the junction sarcoplasmic reticulum (jSR); the global fluid compartment describing balance between ensemble Ca²⁺ release and other Ca²⁺ fluxes in/out cleft space, bulk myoplasm and sarcoplasmic reticulum. The model yields graded SR Ca²⁺ release with high Ca²⁺ gain in response to voltage clamp stimuli, providing good fits to measured cytosolic Ca²⁺-transient data. More importantly, a testing protocol consisting of long repetitive voltage clamp excitations is applied to the model, which consequently shows changes of systolic Ca²⁺ transients associated with the recovery of contraction following a rest in rat ventricular myocytes. The model not only simulates the global Ca²⁺ influx into and efflux from the cell, as directly observed experimentally, it also reveals the Ca²⁺ flux balance related to release-uptake cycle during each systolic CICR period.