Protein kinase C-α and -ε modulate connexin-43 phosphorylation in human heart

Nancy Bowling, Xiao Di Huang, George E. Sandusky, Rebecca L. Fouts, Karen Mintze, Michail Esterman, Paul D. Allen, Rosemarie Maddi, Eileen McCall, Chris J. Vlahos

Research output: Contribution to journalArticlepeer-review

65 Scopus citations


We have previously demonstrated that protein kinase C (PKC)-α expression is significantly elevated in failing human left ventricle, with immunostaining showing increased PKC-α localization at the intercalated disks of cardiomyocytes. In the present study we sought to determine, in the failing heart, if PKC-α interacted with connexin-43 (Cx-43) both spatially and functionally, and to compare the association of PKC-α/Cx-43 with that of PKC-ε, a PKC isozyme that does not significantly increase in failing hearts. The possibility of a PKC-α or PKC-ε/Cx-43 association in non-failing hearts was also investigated. Co-immunoprecipitation of PKC-α or PKC-ε and Cx-43 in non-failing and failing left ventricle was achieved using antibodies to PKC-α or Cx-43. Confocal microscopy confirmed that PKC-α distribution within the cardiomyocyte included co-localization with connexin-43 in both falling and non-failing myocardium. In a similar manner, confocal imaging of PKC-ε showed cardiomyocyte distribution in both cytosol and membrane, and colocalization of PKC-ε with Cx-43. Recombinant PKC-α or -ε increased PKC activity significantly above endogenous levels in the co-immunoprecipitated Cx-43 complexes (P<0.05). However, phosphorylation of purified human Cx-43 (isolated from failing human left ventricle) by recombinant PKC-α or PKC-ε resulted in only PKC-ε mediated Cx-43 phosphorylation. Thus, in the human heart PKC-α, PKC-ε, and Cx-43 appear to form a closely associated complex. Whereas only PKC-ε directly phosphorylates Cx-43, both PKC isoforms result in increased phosphorylation within the Cx-43 co-immunoprecipitated complex.

Original languageEnglish (US)
Pages (from-to)789-798
Number of pages10
JournalJournal of Molecular and Cellular Cardiology
Issue number4
StatePublished - 2001
Externally publishedYes


  • Cardiomyopathy
  • Gap junctions
  • Phosphoprotein
  • Protein kinase
  • Signal transduction

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine


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