Regulation of gap-junction protein connexin 43 by [beta]-adrenergic receptor stimulation in rat cardiomyocytes

• Published in: Acta pharmacologica Sinica Vol. 30; no. 7; p. 928
• Main Authors: Xia, Yi, Gong, Kai-zheng, Xu, Ming, Zhang, You-yi, Guo, Ji-hong, Song, Yao, Zhang, Ping
• Format: Journal Article
• Language: English
• Published: Shanghai Nature Publishing Group 01.07.2009
• ISSN: 1671-4083; 1745-7254
• DOI: 10.1038/aps.2009.92

beta-adrenergic receptor (beta-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 beta-AR subtypes on Cx43 expression and gap junction intercellular communication (GJIC) function. 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. Stimulation of beta-AR by the agonist isoproterenol for 5 min induces the up-regulation of nonphosphorylated Cx43 protein level, but not total Cx43. Selective beta(2)-AR inhibitor ICI 118551, but not beta(1)-AR inhibitor CGP20712, could fully abolish the effect. Moreover, pretreatment with both protein kinase A inhibitor H89 and G(i) 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. Taken together, beta(2)-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 G(i)-dependent manner.Acta Pharmacologica Sinica (2009) 30: 928-934; doi: 10.1038/aps.2009.92.