Contractile activity modulates atrial natriuretic factor gene expression in neonatal rat ventricular myocytes

Diane M. Eble, Brian M. Cadre, Ming Qi, Donald M Bers, Allen M. Samarel

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

[Ca2+](i) transients, and the activation of Ca2+-sensitive kinases have been considered potential signaling mechanisms regulating ANF gene expression in cultured neonatal rat ventricular myocytes (NRVM). However, it is unclear whether [Ca2+](i) is directly involved, or is indirectly involved by generating additional mechanical signals via contractile activity. Primary cultures of spontaneously contracting NRVM (CON), and NRVM treated for 48 h with verapamil (V, 10 μM), KCl (50 mM), or 2,3-butanedione monoxime (BDM, 7.5 mM) were used to delineate the affects of contractile activity v [Ca2+](i). Verapamil, a calcium channel blocker, inhibits contraction and decreases [Ca2+](i). High [K+](o) causes membrane depolarization, loss of contraction, and elevates [Ca2+](i); whereas BDM strongly inhibits contractile activity but only modestly reduces [Ca2+](i) transients. ANF production, as assessed by radioimmunoassay, was significantly reduced upon contractile arrest independently of [Ca2+](i) levels. Northern blotting analysis demonstrated that contractile arrest also reduced ANF mRNA levels. Transient transfection of a 3003 bp ANF promoter-luciferase expression plasmid in CON, V, KCl, and BDM-treated NRVM demonstrated marked down-regulation of ANF promoter activity in all of the contractile arrested myocytes. These results indicate that the activation of Ca2+-sensitive processes alone are insufficient to maintain high levels of ANF gene expression and peptide production in NRVM.

Original languageEnglish (US)
Pages (from-to)55-60
Number of pages6
JournalJournal of Molecular and Cellular Cardiology
Volume30
Issue number1
DOIs
StatePublished - Jan 1998
Externally publishedYes

Keywords

  • Calcium
  • Cardiomyocytes
  • Contraction

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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