Objective:Calcium-sensing receptors(CaSRs)are G-protein coupled receptors which maintain systemic calcium homeostasis and participate in hormone secretion,activation of ion channels,cell apoptosis,proliferation,and differentiation.Previous studies have shown that CaSRs induce apoptosis in isolated adult rat heart and in normal neonatal rat cardiomyocytes by G-protein-PLC-IP 3 signaling transduction.However,little knowledge is presently available concerning the role of CaSRs in the apoptosis induced by ischemia and reperfusion in neonatal cardiomyocytes.Methods:Primary neonatal rat ventricular cardiomyocytes were incubated in ischemiamimetic solution for 2 h,and then re-incubated in normal culture medium for 24 h to establish a model of simu- lated ischemia/reperfusion(I/R).Cardiomyocyte apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL).The expression of CaSRs mRNA was detected by real-time reverse transcription polymerase chain reaction(RT-PCR).In addition,the expressions of caspase-3 and Bcl-2 were analyzed by western blot.Results:The simulated I/R enhanced the expression of CaSRs and cardiomyocyte apopto- sis.GdCl 3 ,a specific activator of CaSRs,further increased the expression of CaSRs and cardiomyocyte apoptosis, along with up-regulation of caspase-3 and down-regulation of Bcl-2.Conclusion:CaSRs are associated with I/R injury and apoptosis in neonatal rat ventricular cardiomyocytes via suppressing Bcl-2 and promoting caspase-3 expression. Objective: Calcium-sensing receptors (CaSRs) are G-protein coupled receptors which maintain system of calcium homeostasis and participate in hormone secretion, activation of ion channels, cell apoptosis, proliferation, and differentiation. Previous studies have shown that CaSRs induce apoptosis in isolated adult Heart and in normal neonatal rat cardiomyocytes by G-protein-PLC-IP 3 signaling transduction. However, little knowledge is presently available concerning the role of CaSRs in the apoptosis induced by ischemia and reperfusion in neonatal cardiomyocytes. Methods: Primary neonatal rat ventricular cardiomyocytes were incubated in ischemiamimetic solution for 2 h, and then re-incubated in normal culture medium for 24 h to establish a model of simu-lated ischemia / reperfusion (I / R). Cardiomyocyte apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). The expression of CaSRs mRNA was detected by real-time reverse transcription polymerase chain react Results: The simulated I / R enhanced the expression of CaSRs and cardiomyocyte apopto- sis. GdCl 3, a specific activator (RT-PCR) .In addition to the expressions of caspase-3 and Bcl- of CaSRs, further increased the expression of CaSRs and cardiomyocyte apoptosis along with up-regulation of caspase-3 and down-regulation of Bcl-2.Conclusion: CaSRs are associated with I / R injury and apoptosis in neonatal rat ventricular cardiomyocytes by suppressing Bcl-2 and promoting caspase-3 expression.