Ups and downs of calcium in the heart

Abstract

Contraction and relaxation of the heart result from cyclical changes of intracellular Ca concentration ([Ca2+]i ). The entry of Ca2+ into the cell via the L-type Ca current leads to the release of more from the sarcoplasmic reticulum (SR). Compared to other regulatory mechanisms such as phosphorylation, calcium signalling is very rapid. However, since Ca2+ cannot be destroyed, Ca signalling can only be controlled by pumping across membranes. In
the steady state, on each beat, the amount of Ca 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 content and this provides a mechanism for regulation of SR Ca content. These flux balance considerations also explain why simply potentiating Ca release from the SR has no maintained effect on the amplitude of the Ca transient. A low
diastolic [Ca2+]i is essential for cardiac relaxation but the factors that control diastolic [Ca2+]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 transient and the resulting decrease of Ca efflux results in an increase of diastolic [Ca2+]i to maintain total
efflux.