Regulation of gap-junction protein connexin 43 by β-adrenergic receptor stimulation in rat cardio- myocytes

β-adrenergic receptor （β-AR） agonists are among the most potent factors regulating cardiac electrophysiological properties. Connexin 43 （Cx43）, the predominant gap-junction protein in the heart, has an indispensable role in modulating cardiac electric activities by affecting gap-junction function. The present study investigates the effects of short-term stimulation of β-AR subtypes on Cx43 expression and gap junction intercellular communication （GJIC） function. Methods： The level of Cx43 expression in neonatal rat cardiomyocytes （NRCM） was detected by a Western blotting assay. The GJIC function was evaluated by scrape loading/dye transfer assay. Results： Stimulation of β-AR by the agonist isoproterenol for 5 min induces the up-regulation of nonphosphorylated Cx43 protein level, but not total Cx43. Selective β2-AR inhibitor ICI 118551, but not β1-AR inhibitor CGP20712, could fully abolish the effect. Moreover, pretreatment with both protein kinase A inhibitor H89 and Gi protein inhibitor pertussis toxin also inhibited the isoproterenol-induced increase of nonphosphorylated Cx43 expression. Isoproterenol-induced up-regulation of nonphosphorylated Cx43 is accompanied with enhanced GJIC function. Conclusion： Taken together, β2-AR stimulation increases the expression of nonphosphorylated Cx43, thereby enhancing the gating function of gap junctions in cardiac myocytes in both a protein kinase A-and G1-dependent manner.