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

AbstractAim: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 Gi-dependent manner.

• Publication year

  2009

• Venue

  Acta Pharmacologica Sinica

• Publication date

  2009-07-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1038/aps.2009.92PMID 19574999PMCID 4006640
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Alpha-1-adrenoceptor subtype selective regulation of connexin 43 expression in rat cardiomyocytes

  2008cited by this paper
• Molecular mechanisms of beta(2)-adrenergic receptor function, response, and regulation.

  2006cited by this paper
• Cardiovascular Effects of -Agonists in Patients With Asthma and COPD*

  2006cited by this paper
• Endurance exercise training attenuates cardiac beta2-adrenoceptor responsiveness and prevents ventricular fibrillation in animals susceptible to sudden death.

  2006cited by this paper
• Induction of beta3-adrenergic receptor functional expression following chronic stimulation with noradrenaline in neonatal rat cardiomyocytes.

  2006cited by this paper
• Induction of β3-Adrenergic Receptor Functional Expression following Chronic Stimulation with Noradrenaline in Neonatal Rat Cardiomyocytes

  2006cited by this paper
• Molecular mechanisms of β2-adrenergic receptor function, response, and regulation

  2006cited by this paper
• Acute electrophysiologic effects of inhaled salbutamol in humans.

  2005cited by this paper
• The role of beta-adrenergic receptor signaling in cardioprotection.

  2005cited by this paper
• The role of β‐Adrenergic Receptor Signaling in Cardioprotection

  2005cited by this paper
• Enhanced Functional Gap Junction Neoformation by Protein Kinase A–Dependent and Epac-Dependent Signals Downstream of cAMP in Cardiac Myocytes

  2005cited by this paper
• 14‐3‐3 Proteins regulate glycogen synthase 3β phosphorylation and inhibit cardiomyocyte hypertrophy

  2005cited by this paper
• Mechanism of regulation of the gap junction protein connexin 43 by protein kinase C-mediated phosphorylation.

  2004cited by this paper
• Cardiovascular effects of beta-agonists in patients with asthma and COPD: a meta-analysis.

  2004cited by this paper
• Gap junctions and the connexin protein family.

  2004cited by this paper
• Electrophysiologic effects of salbutamol, a beta2-selective agonist.

  2004cited by this paper
• Electrical Propagation in Synthetic Ventricular Myocyte Strands From Germline Connexin43 Knockout Mice

  2004cited by this paper
• Electrophysiologic Effects of Salbutamol, a β2‐Selective Agonist

  2004cited by this paper
• Effects of the New Antiarrhythmic Peptide ZP123 on Epicardial Activation and Repolarization Pattern

  2003cited by this paper
• Plasma membrane channels formed by connexins: their regulation and functions.

  2003cited by this paper
• PP2A activation by beta2-adrenergic receptor agonists: novel regulatory mechanism of keratinocyte migration.

  2003cited by this paper
• Inhaled beta-2 adrenergic receptor agonists and primary cardiac arrest.

  2003cited by this paper
• Inhaled beta-2 adrenergic receptor agonists and primary cardiac arrest

  2002cited by this paper
• Pharmacological modulation and differential regulation of the cardiac gap junction proteins connexin 43 and connexin 40

  2002cited by this paper
• The connexin43 gap junction protein is phosphorylated by protein kinase A and protein kinase C: In vivo and in vitro studies

  2002cited by this paper
• Conduction Slowing and Sudden Arrhythmic Death in Mice With Cardiac-Restricted Inactivation of Connexin43

  2001cited by this paper
• The role of myocardial gap junctions in electrical conduction and arrhythmogenesis.

  2001cited by this paper
• Heterogeneous Expression of Gap Junction Channels in the Heart Leads to Conduction Defects and Ventricular Dysfunction

  2001cited by this paper
• Accelerated onset and increased incidence of ventricular arrhythmias induced by ischemia in Cx43-deficient mice.

  2000cited by this paper
• Protein phosphatase activity is increased in a rat model of long-term β-adrenergic stimulation

  2000cited by this paper
• The β2-Adrenergic receptor delivers an antiapoptotic signal to cardiac myocytes through Gi-Dependent coupling to phosphatidylinositol 3'-kinase

  2000cited by this paper
• The beta(2)-adrenergic receptor delivers an antiapoptotic signal to cardiac myocytes through G(i)-dependent coupling to phosphatidylinositol 3'-kinase.

  2000cited by this paper
• Heterogeneous Loss of Connexin43 Protein in Ischemic Dog Hearts

  1999cited by this paper
• Chronic pressure overload cardiac hypertrophy and failure in guinea pigs: III. Intercalated disc remodeling.

  1999cited by this paper
• Blockade by cAMP of native sodium channels of adult rat skeletal muscle fibers.

  1998cited by this paper
• Heart defects in connexin43-deficient mice.

  1998cited by this paper
• Differential Inhibition and Posttranslational Modification of Protein Phosphatase 1 and 2A in MCF7 Cells Treated with Calyculin-A, Okadaic Acid, and Tautomycin*

  1997cited by this paper
• Cardiac malformation in neonatal mice lacking connexin43.

  1995cited by this paper
• Reduced content of connexin43 gap junctions in ventricular myocardium from hypertrophied and ischemic human hearts.

  1993cited by this paper
• Sympathetic stimulation and arrhythmias.

  1991cited by this paper
• Scrape-loading and dye transfer. A rapid and simple technique to study gap junctional intercellular communication.

  1987cited by this paper

• Effects of Renal Denervation on Gap Junction in High-Pacing-Induced Heart Failure Dogs

  2024cites this paper
• Calcineurin-dependent regulation of gap junction conductance and connexin phosphorylation in guinea pig left atrium

  2023cites this paper
• Rat Hepatocytes Mitigate Cadmium Toxicity by Forming Annular Gap Junctions and Degrading Them via Endosome–Lysosome Pathway

  2022cites this paper
• β2-Adrenergic receptor agonist enhances the bystander effect of HSV-TK/GCV gene therapy in glioblastoma multiforme via upregulation of connexin 43 expression

  2022cites this paper
• Modulating mitochondrial dynamics attenuates cardiac ischemia-reperfusion injury in prediabetic rats

  2021cites this paper
• Melatonin improves the maturation and developmental ability of bovine oocytes by up-regulating GJA4 to enhance gap junction intercellular communication.

  2021cites this paper
• β2-Adrenergic Receptor Stimulation Upregulates Cx43 Expression on Glioblastoma Multiforme and Olfactory Ensheathing Cells

  2020cites this paper
• Adrenoceptor Responses in Human Embryonic Stem Cell–Derived Cardiomyocytes: a Special Focus on Electrophysiological Property

  2020cites this paper
• Cardiac extracellular matrix gel for ESC-derived cardiomyocyte maturation

  2020cites this paper
• Cardiac β‐adrenergic receptor activation mediates distinct and cell type‐dependent changes in the expression and distribution of connexin 43

  2020cites this paper
• Regulation of Cardiomyocyte Differentiation, Angiogenesis, and Inflammation by the Delta Opioid Signaling in Human Mesenchymal Stem Cells

  2019cites this paper
• GAP JUNCTIONS: ANOTHER MECHANISM FOR HETEROGENEITY OF REPOLARIZATION ACROSS VENTRICULAR WALL

  2018cites this paper
• Ambient Particulate Matter and Acrolein Co-Exposure Increases Myocardial Dyssynchrony in Mice via TRPA1

  2018cites this paper
• Integration of Gap Junction Coupling in Adenosine Signalling of Endothelial Cells

  2018cites this paper
• Early structural changes of the heart after experimental polytrauma and hemorrhagic shock

  2017cites this paper
• Experimental blunt chest trauma-induced myocardial inflammation and alteration of gap-junction protein connexin 43

  2017cites this paper
• Functional and Transcriptional Characterization of Histone Deacetylase Inhibitor‐Mediated Cardiac Adverse Effects in Human Induced Pluripotent Stem Cell‐Derived Cardiomyocytes

  2016cites this paper
• cAMP-Epac Pathway Stimulation Modulate Connexin-43 and MicroRNA-21 Expression in Glioma Cells

  2015cites this paper
• Pontin, a new mutant p53-binding protein, promotes gain-of-function of mutant p53

  2015cites this paper
• Myocardial electrotonic response to submaximal exercise in dogs with healed myocardial infarctions: evidence for β-adrenoceptor mediated enhanced coupling during exercise testing

  2015cites this paper
• Altered Connexin 43 and Connexin 45 protein expression in the heart as a function of social and environmental stress in the prairie vole

  2015cites this paper
• Gold nanoparticle-mediated (GNOME) laser perforation: a new method for a high-throughput analysis of gap junction intercellular coupling

  2015cites this paper
• Timing is everything in protecting the heart and lungs in a "sympathetic storm": α before β?

  2014cites this paper
• Effects of isoprenaline on endothelial connexins and angiogenesis in a human endothelial cell culture system

  2014cites this paper
• Selective β2 adrenergic agonist increases Cx43 and miR-451 expression via cAMP-Epac.

  2014cites this paper
• Feasibility of allogeneic stem cells for heart regeneration

  2014cites this paper
• A. L. Parker's broadside: laughing "gas" for Littleton.

  2014cites this paper
• New results and controversies about perioperative therapies based on sympathetic blockade or stimulation of various adrenergic receptors will likely help us customize therapies

  2014cites this paper
• VERWENDUNG DES TBX5-PROMOTORS ZUR MAGNET-ANTIKÖRPER BASIERTEN ZELLAUFREINIGUNG (MACS) KARDIALER VORLÄUFERZELLEN AUS EMBRYONALEN STAMMZELLEN

  2013cites this paper
• HYS-32, a novel analogue of combretastatin A-4, enhances connexin43 expression and gap junction intercellular communication in rat astrocytes.

  2013cites this paper
• Mechanisms of Human Atrial Fibrillation Initiation: Clinical and Computational Studies of Repolarization Restitution and Activation Latency

  2012cites this paper
• Aconitine mediates connexin43 and PKC phosphorylation status in cultured ventricular myocytes of neonatal rats

  2011cites this paper
• Characterization of cellular membranes under conditions of ether lipid deficiency

  2011cites this paper
• A high-fat diet increases risk of ventricular arrhythmia in female rats: enhanced

  2010cites this paper
• ILLUSTRATION OF TRANSMEMBRANE RESTING OR DIASTOLIC POTENTIAL IN A CARDIAC CELL AND MEASUREMENT WITH GALVANOMETER

  2010cites this paper
• Cardiac Gap Junction Channels Are Upregulated by Metoprolol: An Unexpected Effect of Beta-Blockers

  2010cites this paper
• A high-fat diet increases risk of ventricular arrhythmia in female rats: enhanced arrhythmic risk in the absence of obesity or hyperlipidemia.

  2010cites this paper
• Gezielte Differenzierung ("Forward Programming") von pluripotenten Stammzellen zu verschiedenen kardiovaskulären Zelltypen

  2010cites this paper