Epsilon protein kinase C lengthens the quiescent period between spontaneous contractions in rat ventricular cardiac myocytes and trabecula

Mourad Ogbi, Christopher J. Wingard, Safia Ogbi, John A Johnson

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

We have observed a lengthening of the duration between spontaneous cardiac contractions under conditions that preferentially activate the epsilon protein kinase C (εPKC) isozyme. Therefore, we investigated whether this response could be selectively mediated by εPKC in neonatal cardiac myocytes (NCMs) and adult rat ventricular trabeculae. Contraction of NCMs was monitored using light scattering techniques and trabecular force generation was monitored in tissue baths using a force transducer. The involvement of the εPKC isozyme was confirmed using an εPKC-selective translocation inhibitor and Western blot translocation assays. In NCMs 3 nM 4-β phorbol 12-myristate-13-acetate (PMA) treatment preferentially activates (translocates) εPKC. In this study 3 nM 4-β PMA induced a 2-fold increase in contractile amplitude and a ∼14-fold increase in the quiescent period between contractions in NCMs. Extracellular adenosine 5′-triphosphate (ATP) also enhanced contractile amplitude by 1.7-fold and the quiescent period duration by 8-fold. The enhancement of quiescent period duration was attenuated by an εPKC-selective translocation inhibitor. To investigate these relationships in intact myocardium, we studied spontaneously beating adult rat ventricular trabecula. In these fibers contractile amplitude was only modestly enhanced; however, the quiescent period was lengthened by 4.5-fold following a 15-min exposure to 3 nM 4-β PMA. 4-β PMA treatment also promoted arrhythmogenesis and increased the association of εPKC with the particulate fraction in these fibers. Our results suggest that εPKC may influence a specific phase of ventricular myocyte spontaneous beating. A better understanding of εPKC modulation of spontaneous cardiac contraction may improve our understanding of the molecular events contributing to ventricular automaticity.

Original languageEnglish (US)
Pages (from-to)251-261
Number of pages11
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume370
Issue number4
DOIs
StatePublished - Oct 1 2004

Keywords

  • Arrhythmia
  • Cardiac myocytes
  • P purinergic
  • Spontaneous contraction
  • Trabecula
  • Translocation inhibitors
  • εPKC

ASJC Scopus subject areas

  • Pharmacology

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