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.