Ryanodine receptor channelopathies.

Abstract

Ryanodine receptors (RyR) are the Ca2+ release channels of sarcoplasmic reticulum that provide the majority of the [Ca2+] necessary to induce contraction of cardiac and skeletal muscle cells. In their cellular environment, RyRs are exquisitely regulated by a variety of cytosolic factors and accessory proteins so that their output signal (Ca2+) induces cell contraction without igniting signaling pathways that eventually lead to contractile dysfunction or pathological cellular remodeling. Here we review how dysfunction of RyRs, most commonly expressed as enhanced Ca2+ release at rest (skeletal muscle) or during diastole (cardiac muscle), appears to be the fundamental mechanism underlying several genetic or acquired syndromes. In skeletal muscle, malignant hyperthermia and central core disease result from point mutations in RYR1, the skeletal isoform of RyRs. In cardiac muscle, RYR2 mutations lead to catecholaminergic polymorphic ventricular tachycardia and other cardiac arrhythmias. Lastly, an altered phosphorylation of the RyR2 protein may be involved in some forms of congestive heart failure.

• Authors: Nancy A Benkusky, Emily F Farrell, Héctor H Valdivia
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 322 Issue 4 Pg. 1280-5 (Oct 01 2004) ISSN: 0006-291X [Print] United States
• PMID: 15336975 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S., Review)
• Copyright: Copyright 2004 Elsevier Inc.

Chemical References

• Ryanodine Receptor Calcium Release Channel
• Calcium

Topics

• Calcium (metabolism)
• Heart Diseases (genetics, metabolism)
• Heart Failure
• Humans
• Malignant Hyperthermia (genetics, metabolism)
• Muscle, Skeletal (metabolism)
• Muscular Diseases (genetics, metabolism)
• Mutation
• Myocardium (metabolism)
• Myopathy, Central Core (genetics, metabolism)
• Ryanodine Receptor Calcium Release Channel (genetics, metabolism)
• Tachycardia, Ventricular