Inhibition of the spontaneous rate of contraction of neonatal cardiac myocytes by protein kinase C isozymes: A putative role for the ε isozyme

John A Johnson, Daria Mochly-Rosen

Research output: Contribution to journalArticle

90 Citations (Scopus)

Abstract

Protein kinase C (PKC) enzymes regulate numerous cardiac functions. In the present study, we determined the effects of the PKC-activating drug 4-β phorbol 12-myristate 13-acetate (4-β PMA) on the rate of contraction and correlated these changes with the distribution and levels of α-, β-, δ-, ε-, and ζ-PKC isozymes by using neonatal rat cardiac myocytes in culture. Treatment with 0.3 to 100 nmol/L 4-β PMA caused negative chronotropic effects on contraction. This effect was maximal at a concentration of 3 nmol/L 4-β PMA and correlated with redistribution of the α- and ε-PKC isozymes from the cytosolic to the particulate cell fraction. After a 1-hour treatment with 100 nmol/L PMA, the α- and β-PKC isozymes and an 80-kD ζ- like PKC isozyme were greatly diminished (downregulated), yet the negative chronotropic effect was sustained. Therefore, our results are most consistent with a role for the ε-PKC isozyme in suppressing the contraction rate of neonatal rat cardiac myocytes. Understanding the role(s) of individual PKC isozymes in the modulation of cardiac functions may ultimately yield more selective targets for therapies of cardiac disorders.

Original languageEnglish (US)
Pages (from-to)654-663
Number of pages10
JournalCirculation Research
Volume76
Issue number4
DOIs
StatePublished - Jan 1 1995
Externally publishedYes

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Cardiac Myocytes
Protein Kinase C
Isoenzymes
Acetates
Down-Regulation
Enzymes
Pharmaceutical Preparations
phorbol-12-myristate

Keywords

  • cardiac myocytes
  • contraction
  • heart
  • phorbol ester
  • protein kinase C isozymes

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Inhibition of the spontaneous rate of contraction of neonatal cardiac myocytes by protein kinase C isozymes : A putative role for the ε isozyme. / Johnson, John A; Mochly-Rosen, Daria.

In: Circulation Research, Vol. 76, No. 4, 01.01.1995, p. 654-663.

Research output: Contribution to journalArticle

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