Abstract
Contraction and relaxation of the heart result from cyclical changes of intracellular Ca(2+) concentration ([Ca(2+) ](i) ). The entry of Ca(2+) into the cell via the L-type Ca(2+) current leads to the release of more from the sarcoplasmic reticulum (SR). Compared to other regulatory mechanisms such as phosphorylation, Ca(2+) signalling is very rapid. However, since Ca(2+) cannot be destroyed, Ca(2+) signalling can only be controlled by pumping across membranes. In the steady state, on each beat, the amount of Ca(2+) released from the SR must equal that taken back and influx and efflux across the sarcolemma must be equal. Any imbalance in these fluxes will result in a change of SR Ca(2+) content and this provides a mechanism for regulation of SR Ca(2+) content. These flux balance considerations also explain why simply potentiating Ca(2+) release from the SR has no maintained effect on the amplitude of the Ca(2+) transient. A low diastolic [Ca(2+) ](i) is essential for cardiac relaxation, but the factors that control diastolic [Ca(2+) ](i) are poorly understood. Recent work suggests that flux balance is also important here. In particular, decreasing SR function decreases the amplitude of the systolic Ca(2+) transient and the resulting decrease of Ca(2+) efflux results in an increase of diastolic [Ca(2+) ](i) to maintain total efflux.