Acta Pharmacologica Sinica (2009) 30: 928-934; doi: 10.1038/aps.2009.92

Aim: 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 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. 

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 G_i-dependent manner. 

Keywords: connexin43; gap junction; β-adrenergic receptor; cardiac myocyte