The sarcoplasmic reticulum and arrhythmogenic calcium release

There is much evidence showing that some lethal ventricular arrhythmias arise from waves of Ca2+ release from the sarcoplasmic reticulum (SR) that propagate along cardiac cells. The purpose of this review is to discuss the mechanism of production of these waves and how they depend on the properties of the SR Ca2+ release channel or ryanodine receptor (RyR). The best-known method of producing Ca2+ waves is by increasing the Ca2+ content of the cell by either increasing Ca2+ influx or decreasing efflux. Once SR Ca2+ content reaches a threshold level a Ca2+ wave is produced. Altering the properties of the RyR affects the threshold level of Ca2+ required to produce a wave. Patients with a mutation in the RyR suffer from catecholaminergic polymorphic ventricular tachycardia, and this may be due to a decrease in the SR Ca2+ threshold for wave production. Heart failure has also been suggested to result in Ca2+ waves due to a leak of Ca2+ through the RyR. We review the finding that these changes in RyR function will only result in Ca2+ waves in the steady state if some other mechanism maintains the SR Ca2+ content. The review concludes with a description of potential mechanisms for treating arrhythmias produced by Ca2+ waves.