Ups and downs of calcium in the heart

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. (Figure presented.).