Calcium and cardiomyopathies.
Regulation of Calcium (Ca) cycling by the sarcoplasmic reticulum (SR) underlies the control of cardiac contraction during excitation-contraction (E-C) coupling. Moreover, alterations in E-C coupling occurring in cardiac hypertrophy and heart failure are characterized by abnormal Ca-cycling through the SR network. A large body of evidence points to the central role of: a) SERCA and its regulator phospholamban (PLN) in the modulation of cardiac relaxation; b) calsequestrin in the regulation of SR Ca-load; and c) the ryanodine receptor (RyR) Ca-channel in the control of SR Ca-release. The levels or activity of these key Ca-handling proteins are altered in cardiomyopathies, and these changes have been linked to the deteriorated cardiac function and remodeling. Furthermore, genetic variants in these SR Ca-cycling proteins have been identified, which may predispose to heart failure or fatal arrhythmias. This chapter concentrates on the pivotal role of SR Ca-cycling proteins in health and disease with specific emphasis on their recently reported genetic modifiers.
Kranias
E G
EG
Department of Pharmacology & Cell Biophysics, College of Medicine,University of Cincinnati, OH 45267-0575, USA. Litsa.kranias@uc.edu
Bers
D M
DM
D002118:Calcium / Q000502:physiology*; D020013:Calcium Signaling; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000502:physiology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000502:physiology; D002155:Calsequestrin / Q000235:genetics; D009202:Cardiomyopathies / Q000235:genetics / Q000503:physiopathology*; D006333:Heart Failure / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D009154:Mutation; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D019837:Ryanodine Receptor Calcium Release Channel / Q000502:physiology; D012519:Sarcoplasmic Reticulum / Q000502:physiology; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics / Q000502:physiology; D000099211:Phospholamban
D002118:Calcium; D002135:Calcium-Binding Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002155:Calsequestrin; D011943:Receptors, Adrenergic, beta; D019837:Ryanodine Receptor Calcium Release Channel; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000099211:Phospholamban