β-Adrenergic regulation of a myocardial actin gene via a cyclic AMP- independent pathway

N. H. Bishopric, B. Sato, K. A. Webster

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

The skeletal α-actin gene encodes a major component of the embryonic cardiac sarcomere that is strongly and selectively re-induced during β-adrenoceptor-mediated hypertrophy in neonatal rat cardiac myocytes. We present evidence that β-adrenergic induction of this gene is mediated, not by cAMP, but by a calcium-dependent pathway involving ryanodine-sensitive calcium stores. Nifedipine-induced blockade of the plasma membrane L-type calcium entry channel prevented induction of skeletal α-actin mRNA by isoproterenol. Activation of calcium entry by the dihydropyridine agonist Bay K8644 independently induced skeletal α-actin mRNA, as did cholera toxin-mediated activation of Gs. Induction of skeletal α-actin mRNA by compounds that directly elevate cAMP was weak relative to their effects on other cAMP-dependent phenomena and required calcium entry. In addition, selective inhibition of protein kinase A with KT5720 did not block β-adrenergic induction of skeletal α-actin. Calcium ionophore A23187 did not induce skeletal actin, but prevented its induction by isoproterenol. Ryanodine had bimodal effects: 10-10 M ryanodine induced skeletal α-actin mRNA, whereas 10-6 M ryanodine prevented skeletal actin induction by β-adrenergic stimuli. We postulate that β-adrenergic stimulation of skeletal α-actin mRNA requires G-protein-coupled calcium channel activation and compartmentalized calcium release in a manner independent of the cAMP/protein kinase A signal pathway.

Original languageEnglish (US)
Pages (from-to)20932-20936
Number of pages5
JournalJournal of Biological Chemistry
Volume267
Issue number29
StatePublished - Oct 30 1992

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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