Ups and downs of calcium in the heart

Contraction and relaxation of the heart result from cyclical changes of intracellular Ca2+ concentration ([Ca2+]i). The entry of Ca2+ into the cell via the L‐type Ca2+ current leads to the release of more from the sarcoplasmic reticulum (SR). Compared to other regulatory mechanisms such as phosphorylation, Ca2+ signalling is very rapid. However, since Ca2+ cannot be destroyed, Ca2+ signalling can only be controlled by pumping across membranes. In the steady state, on each beat, the amount of Ca2+ 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 Ca2+ content and this provides a mechanism for regulation of SR Ca2+ content. These flux balance considerations also explain why simply potentiating Ca2+ release from the SR has no maintained effect on the amplitude of the Ca2+ 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 Ca2+ transient and the resulting decrease of Ca2+ efflux results in an increase of diastolic [Ca2+]i to maintain total efflux. Flow diagram showing Ca2+ flux balance illustrating the response to a situation in which Ca2+ influx exceeds efflux. With normal SR function this will increase SR Ca2+ content and increase systolic [Ca2+]i. If SR function is impaired there will be an increase of diastolic [Ca2+]i. In both cases this will result in an increase of Ca2+ efflux such that efflux equals influx.