Myosin heavy chain gene expression in neonatal rat heart cells: Effects of [Ca2+]i and contractile activity

Q. I. Ming, José L. Puglisi, Kenneth L. Byron, Kaie Ojamaa, Irwin Klein, Donald M Bers, Allen M. Samarel

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

To determine if mechanical signals or alterations in intracellular Ca2+ concentration ([Ca2+]i) affect myosin heavy chain (MHC) gene expression in spontaneously beating, neonatal rat ventricular myocytes, contractile activity was inhibited with verapamil, KCl, or 2,3-butanedione monoxime (BDM), and their acute and chronic effects on myocyte shortening, [Ca2+]i, and MHC gene expression were examined. Despite their differing effects on [Ca2+]i; verapamil, KC1, and BDM all inhibited contractile activity and markedly downregulated ß-MHC mRNA levels to 24 5, 21 7, and 6 2% of contracting cells, respectively. In contrast, these inhibitors of contraction upregulated a-MHC mRNA levels to 163 19, 156 7, and 198 20% of contracting cells, respectively. Transient transfection with a rat ß-MHC promoter-luciferase expression plasmid demonstrated that all inhibitors of contraction significantly decreased ß-MHC promoter activity. Paradoxically, contractile arrest also inhibited α-MHC promoter activity, suggesting that increased α-MHC mRNA levels resulted from posttranscriptional mechanisms. Actinomycin D rnRNA stability assays indicated that α-MHC mRNA half-life was prolonged in noncontracting cells (33 h) compared with contracting myocytes (14 h). Contraction-dependent alterations in MHC gene expression were not dependent on release of angiotensin or other growth factors into the culture medium. Thus intrinsic mechanical signals rather than alterations in [Ca2+]j regulate α-MHC and ß-MHC gene expression by both transcriptional and posttranscriptional mechanisms.

Original languageEnglish (US)
JournalAmerican Journal of Physiology
Volume273
Issue number2 PART 1
StatePublished - 1997
Externally publishedYes

Keywords

  • Angiotensin II
  • Calcium
  • Indo 1
  • Intracellular calcium concentration
  • Signal transduction
  • Transcription
  • Verapamil

ASJC Scopus subject areas

  • Physiology (medical)

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    Ming, Q. I., Puglisi, J. L., Byron, K. L., Ojamaa, K., Klein, I., Bers, D. M., & Samarel, A. M. (1997). Myosin heavy chain gene expression in neonatal rat heart cells: Effects of [Ca2+]i and contractile activity. American Journal of Physiology, 273(2 PART 1).