Sarcoplasmic reticulum calcium leak and cardiac arrhythmias Export

@article{citeulike:2906465, abstract = {Abstract Ventricular arrhythmias deteriorating into sudden cardiac death are a major cause of mortality worldwide. The recent linkage of a genetic form of cardiac arrhythmia to mutations in the gene encoding RyR2 (ryanodine receptor 2) has uncovered an important role of this SR (sarcoplasmic reticulum) calcium release channel in triggering arrhythmias. Mutant RyR2 channels give rise to spontaneous release of calcium (Ca2+) from the SR during diastole, which enhances the probability of ventricular arrhythmias. Several molecular mechanisms have been proposed to explain the gain-of-function phenotype observed in mutant RyR2 channels. Despite considerable differences between the models discussed in the present review, each predicts spontaneous diastolic Ca2+ leak from the SR due to incomplete closure of the RyR2 channel. Enhanced SR Ca2+ leak is also observed in common structural diseases of the heart, such as heart failure. In heart failure, defective channel regulation in the absence of inherited mutations may also increase SR Ca2+ leak and initiate cardiac arrhythmias. Therefore inhibition of diastolic Ca2+ leak through SR Ca2+ release channels has emerged as a new and promising therapeutic target for cardiac arrhythmias.}, author = {Chelu, M. G. and Wehrens, H. T.}, citeulike-article-id = {2906465}, citeulike-linkout-0 = {http://www.biochemsoctrans.org/bst/035/bst0350952.htm}, journal = {Biochemical Society Transactions}, keywords = {calcium, camkii, cardiac-arrhythmia, ecc, heart-failure, review, ryr-mutations, ryr-regulation, sarcoplasmic-reticulum, sr-leak, sr-load, ventricular-tachycardia}, number = {5}, pages = {952--956}, posted-at = {2008-06-19 04:10:25}, priority = {0}, title = {Sarcoplasmic reticulum calcium leak and cardiac arrhythmias}, url = {http://www.biochemsoctrans.org/bst/035/bst0350952.htm}, volume = {35}, year = {2007} }

TY - JOUR ID - citeulike:2906465 L3 - citeulike-article-id:2906465 N2 - Abstract Ventricular arrhythmias deteriorating into sudden cardiac death are a major cause of mortality worldwide. The recent linkage of a genetic form of cardiac arrhythmia to mutations in the gene encoding RyR2 (ryanodine receptor 2) has uncovered an important role of this SR (sarcoplasmic reticulum) calcium release channel in triggering arrhythmias. Mutant RyR2 channels give rise to spontaneous release of calcium (Ca2+) from the SR during diastole, which enhances the probability of ventricular arrhythmias. Several molecular mechanisms have been proposed to explain the gain-of-function phenotype observed in mutant RyR2 channels. Despite considerable differences between the models discussed in the present review, each predicts spontaneous diastolic Ca2+ leak from the SR due to incomplete closure of the RyR2 channel. Enhanced SR Ca2+ leak is also observed in common structural diseases of the heart, such as heart failure. In heart failure, defective channel regulation in the absence of inherited mutations may also increase SR Ca2+ leak and initiate cardiac arrhythmias. Therefore inhibition of diastolic Ca2+ leak through SR Ca2+ release channels has emerged as a new and promising therapeutic target for cardiac arrhythmias. IS - 5 JF - Biochemical Society Transactions EP - 956 TI - Sarcoplasmic reticulum calcium leak and cardiac arrhythmias VL - 35 SP - 952 KW - calcium KW - camkii KW - cardiac-arrhythmia KW - ecc KW - heart-failure KW - review KW - ryr-mutations KW - ryr-regulation KW - sarcoplasmic-reticulum KW - sr-leak KW - sr-load KW - ventricular-tachycardia AU - Chelu, MG AU - Wehrens, HT PY - 2007/// UR - http://www.biochemsoctrans.org/bst/035/bst0350952.htm ER -