Aim:The enhancement of intracellular Ca~(2+) signaling in response to α_1-adrener-gic receptor (α_1-AR) stimulation is an essential signal transduction event in theregulation of cardiac functions,such as cardiac growth,cardiac contraction,andcardiac adaptation to various situations.The present study was intended todetermine the role(s) of the α_1-AR subtype(s) in mediating this response.Methods:We evaluated the effects of subtype-specific agonists and antagonists of the α_1-AR on the intracellular Ca~(2+) signaling of neonatal rat ventricular myocytes usinga confocal microscope.Results:After being cultured for 48 h,the myocytesexhibited spontaneous local Ca~(2+) release,sparks,and global Ca~(2+) transients.Theactivation of the α_1-AR with phenylephrine,a selective agonist of the α_1-AR,dose-dependently increased the frequency of Ca~(2+) transients with an EC_(50) valueof 2.3 μmol/L.Blocking the α_(1A)-AR subtype with 5-methylurapidil (5-Mu) inhi-bited the stimulatory effect of phenylephrine with an IC_(50) value of 6.7 nmol/L.Incontrast,blockade of the α_(1B)-AR and α_(1D)-AR subtypes with chloroethylclonidineand BMY 7378,respectively,did not affect the phenylephrine effect.Similarly,thelocal Ca~(2+) spark numbers were also increased by the activation of the α_1-AR,andthis effect could be abolished selectively by 5-Mu.More importantly,A61603,anovel selective α_(1A)-AR agonist,mimicked the effects of phenylephrine,but withmore potency (EC_(50) value=6.9 nmol/L) in the potentiation of Ca~(2+) transients,andblockade of the α_(1A)-AR by 5-Mu caused abolishment of its effects.Conclusion:These results indicate that α_1-adrenergic stimulation of intracellular Ca~(2+) activityis mediated selectively by the α_(1A)-AR. Aim: The enhancement of intracellular Ca ~ (2+) signaling in response to α_1-adrener-gic receptor (α_1-AR) stimulation is an essential signal transduction event in thereiment of cardiac functions, such as cardiac growth, cardiac contraction, and cardiac adaptation to various situations. The present study was intended to define the role (s) of the α_1-AR subtype (s) in mediating this response. Methods: We evaluated the effects of subtype-specific agonists and antagonists of the α_1-AR on the intracellular Ca 2+ signaling of neonatal rat ventricular myocytes using confocal microscope. Results: After being cultured for 48 h, the myocytesexhibited spontaneous local Ca 2+ release, sparks, and global Ca 2+ transients. Activation of the α_1-AR with phenylephrine, a selective agonist of the α_1-AR, dose-dependently increased the frequency of Ca 2+ transients with an EC_ (50) value of 2.3 μmol / L. Blocking the α_ (1A) - AR subtype with 5-methylurapidil (5-Mu) inhi-bited the stimulatory effect of Phenylephrine with an IC 50 (50) value of 6.7 nmol / L. Incontrast, blockade of the alpha - (1B) -AR and alpha - (1D) - AR subtypes with chloroethylclonidine and BMY 7378, respectively, did not affect the phenylephrine effect. Ca 2+ spark numbers were also increased increased by the activation of α_1-AR, and effect could be abolished selectively by 5-Mu. Importantly, A61603, anovel selective α_ (1A) -AR agonist, mimicked the effects of Phenylephrine, but with more potency (EC 50 (50) value = 6.9 nmol / L) in the potentiation of Ca 2+ transients, and blockade of the α 1A 1A by 5-Mu caused abolishment of its effects. Confclusion: These results indicate that α_1-adrenergic stimulation of intracellular Ca 2+ activityis mediated selectively by the α_ (1A) -AR.