title: Stimulatory action of protein kinase C(epsilon) isoform on the slow component of delayed rectifier K+ current in guinea-pig atrial myocytes.
abstract: OBJECTIVE
  Protein kinase C (PKC) comprises at least twelve isoforms and has an isoform-specific action on cardiac electrical activity. The slow component of delayed rectifier K(+) current (I (Ks)) is one of the major repolarizing currents in the hearts of many species and is also potentiated by PKC activation. Little is known, however, about PKC isoform(s) functionally involved in the potentiation of I (Ks) in native cardiac myocytes.
  
  
  METHODS
  I (Ks) was recorded from guinea-pig atrial myocytes, using the whole-cell configuration of patch-clamp method.
  
  
  RESULTS
  Bath application of phenylephrine enhanced I (Ks) concentration-dependently with EC(50) of 5.4 microM and the maximal response (97.1+/-11.9% increase, n=16) was obtained at 30 microM. Prazosin (1 microM) almost totally abolished the potentiation of I (Ks) by phenylephrine, supporting the involvement of alpha(1)-adrenoceptors. The stimulatory action of phenylephrine was significantly, if not entirely, inhibited by the general PKC inhibitor bisindolylmaleimide I but was little affected by Gö-6976, Gö-6983 and rottlerin. Furthermore, this stimulatory effect was significantly reduced by dialyzing atrial myocytes with PKCepsilon-selective inhibitory peptide epsilonV1-2 but was not significantly affected by conventional PKC isoform-selective inhibitory peptide betaC2-4. Phorbol 12-myristate 13-acetate (PMA) at 100 nM substantially increased I (Ks) by 64.2+/-1.3% (n=6), which was also significantly attenuated by an internal dialysis with epsilonV1-2 but not with betaC2-4.
  
  
  CONCLUSIONS
  The present study provides experimental evidence to suggest that, in native guinea-pig cardiac myocytes, activation of PKC contributes to alpha(1)-adrenoceptor-mediated potentiation of I (Ks) and that epsilon is the isoform predominantly involved in this PKC action.
authors.affiliation: Department of Physiology, Shiga University of Medical Science, Otsu, Shiga, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Toda
authors.forename: W-G
authors.initials: WG
authors.lastname: Ding
authors.forename: Y
authors.initials: Y
authors.lastname: Yasuda
authors.forename: F
authors.initials: F
authors.lastname: Toyoda
authors.forename: M
authors.initials: M
authors.lastname: Ito
authors.forename: H
authors.initials: H
authors.lastname: Matsuura
authors.forename: M
authors.initials: M
authors.lastname: Horie
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D051668:Delayed Rectifier Potassium Channels / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D006168:Guinea Pigs; D006325:Heart Atria / Q000166:cytology / Q000378:metabolism; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism; D008301:Maleimides / Q000494:pharmacology; D008564:Membrane Potentials; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051744:Protein Kinase C-epsilon / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D051668:Delayed Rectifier Potassium Channels; D007211:Indoles; D007527:Isoenzymes; D008301:Maleimides; D010446:Peptide Fragments; D047428:Protein Kinase Inhibitors; D018340:Receptors, Adrenergic, alpha-1; C448318:epsilonV1-2 peptide; D010656:Phenylephrine; D051744:Protein Kinase C-epsilon; C070515:bisindolylmaleimide I; D013755:Tetradecanoylphorbol Acetate; D011224:Prazosin