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Effects of carvedilol on RyR2-mediated spontaneous calcium oscillation
Authors:XIAO Jian-min  FU Hui
Institution:1.Department of Cardiovascular Medicine, Dongguan Taiping People’s Hospital, Dongguan 523905, China;2.Department of Pharmacology, Guangdong Medical College, Dongguan 523808, China.
Abstract:AIM:To investigate the effects of carvedilol and other β-blockers on ryanodine receptor 2(RyR2)-mediated spontaneous calcium oscillation.
METHODS:HEK293 cells, which steadily and inducibly expressed RyR2, were generated using the Flp-In T-REx Core Kit. Single rat ventricular myocyte was isolated by the method of collagenase. The extracellular Ca2+ concentration was increased step by step to induce calcium oscillation. Single cell calcium imaging was used to test the effects of carvedilol and other β-blockers on RyR2-mediated spontaneous cal-cium oscillation in cardiac cells and HEK293 cells. RESULTS:Carvedilol at concentration of 30 μmol/L obviously suppressed the spontaneous cal-cium oscillation in cardiac cells and HEK293 cells expressing RyR2. The inhibitory rate was (6530±230)% and (6908±530)%, respectively. Metoprolol and other β-blockers had no effects on spontaneous calcium oscillation in cardiac cells and HEK293 cells. CONCLUSION:Carvedilol is the only β-blocker that suppresses RyR2-mediated spontaneous calcium oscillation. This may be one of the mechanisms that carvedilol is better than other β-blockers in reducing the mortality of heart failure.
Keywords:Carvedilol  Cardiomyocytes  HEK293 cells  Spontaneous calcium oscillation  
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