Delayed afterdepolarization;

There is much evidence showing that some lethal ventricular arrhythmias arise from waves of Ca2þ 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 Ca2þ release channel or ryanodine receptor (RyR). The best-known method of producing Ca2þ waves is by increasing the Ca2þ content of the cell by either increasing Ca2þ influx or decreasing efflux. Once SR Ca2þ content reaches a threshold level a Ca2þ wave is produced. Altering the properties of the RyR affects the threshold level of Ca2þ 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 Ca2þ threshold for wave production. Heart failure has also been suggested to result in Ca2þ waves due to a leak of Ca2þ through the RyR. We review the finding that these changes in RyR function will only result in Ca2þ waves in the steady state if some other mechanism maintains the SR Ca2þ content. The review concludes with a description of potential mechanisms for treating arrhythmias produced by Ca2þ waves