title: The sarcoplasmic reticulum and arrhythmogenic calcium release.
abstract: There is much evidence showing that some lethal ventricular arrhythmias arise from waves of Ca(2+) 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 Ca(2+) release channel or ryanodine receptor (RyR). The best-known method of producing Ca(2+) waves is by increasing the Ca(2+) content of the cell by either increasing Ca(2+) influx or decreasing efflux. Once SR Ca(2+) content reaches a threshold level a Ca(2+) wave is produced. Altering the properties of the RyR affects the threshold level of Ca(2+) 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 Ca(2+) threshold for wave production. Heart failure has also been suggested to result in Ca(2+) waves due to a leak of Ca(2+) through the RyR. We review the finding that these changes in RyR function will only result in Ca(2+) waves in the steady state if some other mechanism maintains the SR Ca(2+) content. The review concludes with a description of potential mechanisms for treating arrhythmias produced by Ca(2+) waves.
authors.affiliation: Unit of Cardiac Physiology, University of Manchester, Core Technology Facility, 46 Grafton St, Manchester M13 9NT, UK.
authors.forename: Luigi A
authors.initials: LA
authors.lastname: Venetucci
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Trafford
authors.forename: Stephen C
authors.initials: SC
authors.lastname: O'Neill
authors.forename: David A
authors.initials: DA
authors.lastname: Eisner
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D006801:Humans; D009154:Mutation; D010766:Phosphorylation; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics / Q000502:physiology; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000502:physiology
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D002118:Calcium