A mathematical model of Ca/sup 2+/-release and Ca/sup 2+/ balance during systole in rat ventricular myocytes

摘要

It is well-established that mammalian cardiac excitation-contraction coupling is mediated by Ca/sup 2+/-induced Ca/sup 2+/ release (CICR). We have developed a lumped equivalent component model of the I/sub Ca,L/ trigger Ca/sup 2+/ release process that includes component models of Ca/sup 2+/ diffusion in the local representative dyadic cleft space; Ca/sup 2+/ release from local representative release complex on the junction sarcoplasmic reticulum (jSR); the global fluid compartment describing balance between ensemble Ca/sup 2+/ release and other Ca/sup 2+/ fluxes in/out cleft space, bulk myoplasm and sarcoplasmic reticulum. The model yields graded SR Ca/sup 2+/ release with high Ca/sup 2+/ gain in response to voltage clamp stimuli, providing good fits to measured cytosolic Ca/sup 2+/-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 Ca/sup 2+/ transients associated with the recovery of contraction following a rest in rat ventricular myocytes. The model not only simulates the global Ca/sup 2+/ influx into and efflux from the cell, as directly observed experimentally, it also reveals the Ca/sup 2+/ flux balance related to release-uptake cycle during each systolic CICR period.