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

作　　者：Yi XIA Kai-zheng GONG Ming XU You-yi ZHANG Ji-hong GUO Yao SONG Ping ZHANG 

机构地区：[1]Electrophysiology Laboratory, Department of Cardiology, Peking University People's Hospital, Beijing 100044, China [2]Institute of Vascular Medicine, Peking University Third Hospital, Beijing 1001910191, China4 [3]Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, China

出　　处：《Acta Pharmacologica Sinica》2009年第7期928-934,共7页中国药理学报（英文版）

基　　金：Acknowledgements This work was supported by the National Key Basic Research Program （NKBRP） of People＇s Republic of China （No 2006CB503806, 2007CB512008）, the National Natural Science Foundation of China （No 30471916, 30821001） and Beijing Municipal Natural Science Foundation （No 7052045）.

摘　　要：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.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.

关 键 词：CONNEXIN43 gap junction β-adrenergic receptor cardiac myocyte 

分 类 号：Q555.7[生物学—生物化学] Q577