Roles of cardiac ryanodine receptor in heart failure and sudden cardiac death.
Calcium (Ca2+) plays an important role as a messenger in the excitation-contraction coupling process of the myocardium. It is stored in the sarcoplasmic reticulum (SR) and released via a calcium release channel called the ryanodine receptor. Cardiac ryanodine receptor (RyR2) controls Ca2+ release, which is essential for cardiac contractility. There are several molecules which bind and regulate the function of RyR2 including calstabin2, calmodulin, protein kinase A (PKA), phosphatase, sorcin and calsequestrin. Alteration of RyR2 and associated molecules can cause functional and/or structural changes of the heart, leading to heart failure and sudden cardiac death. In this review, the alteration of RyR2 and its regulatory proteins, and its roles in heart failure and sudden cardiac death, are discussed. Evidence of a possible novel therapy targeting RyR2 and its associated regulatory proteins, currently proposed by investigators, is also included in this article.
Phrommintikul
Arintaya
A
Department of Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
Chattipakorn
Nipon
N
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002135:Calcium-Binding Proteins / Q000502:physiology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000502:physiology; D002395:Catecholamines / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D016757:Death, Sudden, Cardiac; D006333:Heart Failure / Q000503:physiopathology*; D006801:Humans; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism; D010766:Phosphorylation; D019837:Ryanodine Receptor Calcium Release Channel / Q000502:physiology*; D012508:Sarcolemma / Q000502:physiology; D013564:Sympathetic Nervous System / Q000469:parasitology; D022021:Tacrolimus Binding Proteins / Q000502:physiology
D002135:Calcium-Binding Proteins; D002395:Catecholamines; D019837:Ryanodine Receptor Calcium Release Channel; C503113:SRI protein, human; D017868:Cyclic AMP-Dependent Protein Kinases; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D022021:Tacrolimus Binding Proteins; C403484:tacrolimus binding protein 1B; D002118:Calcium