Heart Rhythm
Volume 6, Issue 11 , Pages 1632-1638 , November 2009

Phosphorylation of connexin43 on serine 306 regulates electrical coupling

  • Kristina Procida, MD

      Affiliations

    • Danish National Research Foundation Centre for Cardiac Arrhythmia at Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
    • ,
  • Lone Jørgensen, MS

      Affiliations

    • Danish National Research Foundation Centre for Cardiac Arrhythmia at Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
    • ,
  • Nicole Schmitt, PhD

      Affiliations

    • Danish National Research Foundation Centre for Cardiac Arrhythmia at Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
    • ,
  • Mario Delmar, MD, PhD, FHRS

      Affiliations

    • Center for Arrhythmia Research, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan
    • ,
  • Steven M. Taffet, PhD

      Affiliations

    • Department of Microbiology and Immunology, SUNY Upstate Medical University, Syracuse, New York
    • ,
  • Niels-Henrik Holstein-Rathlou, MD, PhD

      Affiliations

    • Danish National Research Foundation Centre for Cardiac Arrhythmia at Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
    • ,
  • Morten Schak Nielsen, PhD

      Affiliations

    • Danish National Research Foundation Centre for Cardiac Arrhythmia at Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
    • Corresponding Author InformationAddress reprint requests and correspondence: Dr. Morten Schak Nielsen, The Danish National Research Foundation Centre for Cardiac Arrhythmia at Department of Biomedical Sciences, University of Copenhagen, Blegdamsvej 3, Building 10.5, DK-2200 Copenhagen, Denmark
    • ,
  • Thomas Hartig Braunstein, PhD

      Affiliations

    • Danish National Research Foundation Centre for Cardiac Arrhythmia at Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark

Received 12 February 2009 ,Accepted 24 July 2009.

References 

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  3. Gutstein DE, Morley GE, Tamaddon H, et al. Conduction slowing and sudden arrhythmic death in mice with cardiac-restricted inactivation of connexin43. Circ Res. 2001;88:333–339
  4. Kleber AG, Riegger CB, Janse MJ. Electrical uncoupling and increase of extracellular resistance after induction of ischemia in isolated, arterially perfused rabbit papillary muscle. Circ Res. 1987;61:271–279
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  9. Massey KD, Minnich BN, Burt JM. Arachidonic acid and lipoxygenase metabolites uncouple neonatal rat cardiac myocyte pairs. Am J Physiol. 1992;263:C494–C501
  10. Hofgaard JP, Banach K, Mollerup S, et al. Phosphatidylinositol-bisphosphate regulates intercellular coupling in cardiac myocytes. Pflugers Arch. 2008;457:303–313
  11. Axelsen LN, Stahlhut M, Mohammed S, et al. Identification of ischemia-regulated phosphorylation sites in connexin43: A possible target for the antiarrhythmic peptide analogue rotigaptide (ZP123). J Mol Cell Cardiol. 2006;40:790–798
  12. Lampe PD, Cooper CD, King TJ, et al. Analysis of connexin43 phosphorylated at S325, S328 and S330 in normoxic and ischemic heart. J Cell Sci. 2006;119:3435–3442
  13. Solan JL, Marquez-Rosado L, Sorgen PL, Thornton PJ, Gafken PR, Lampe PD. Phosphorylation at S365 is a gatekeeper event that changes the structure of Cx43 and prevents down-regulation by PKC. J Cell Biol. 2007;179:1301–1309
  14. Xing D, Kjølbye AL, Nielsen MS, et al. ZP123 increases gap junctional conductance and prevents reentrant ventricular tachycardia during myocardial ischemia in open chest dogs. J Cardiovasc Electrophysiol. 2003;14:510–520
  15. Musil LS, Goodenough DA. Biochemical analysis of connexin43 intracellular transport, phosphorylation, and assembly into gap junctional plaques. J Cell Biol. 1991;115:1357–1374
  16. Van Slyke JK, Musil LS. Analysis of connexin intracellular transport and assembly. Methods. 2000;20:156–164
  17. Kwak BR, van Veen TA, Analbers LJS, et al. TPA increases conductance but decreases permeability in neonatal rat cardiomyocyte gap junction channels. Exp Cell Res. 1995;220:456–463
  18. Lampe PD, TenBroek EM, Burt JM, et al. Phosphorylation of connexin43 on serine368 by protein kinase C regulates gap junctional communication. J Cell Biol. 2000;149:1503–1512
  19. Solan JL, Fry MD, TenBroek EM, Lampe PD. Connexin43 phosphorylation at S368 is acute during S and G2/M and in response to protein kinase C activation. J Cell Sci. 2003;116:2203–2211
  20. Laird DW, Puranam KL, Revel JP. Turnover and phosphorylation dynamics of connexin43 gap junction protein in cultured cardiac myocytes. Biochem J. 1991;273:67–72

 The last two authors contributed equally to this study.

 This work was supported by The Danish National Research Foundation; The John and Birthe Meyer Foundation; The Danish Health Sciences Research Councils; The Velux Foundation; The Danish Heart Association; The Novo Nordisk Foundation; and The A.P. Møller Foundation. M.D. was supported by NIH grants GM057691-12, HL039707, and HL087226.

PII: S1547-5271(09)00824-8

doi: 10.1016/j.hrthm.2009.07.043

Heart Rhythm
Volume 6, Issue 11 , Pages 1632-1638 , November 2009

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