Myosin heavy chain gene expression in neonatal rat heart cells

Effects of [Ca2+](i) and contractile activity

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

Research output: Contribution to journalArticle

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, KCl, and BDM all inhibited contractile activity and markedly downregulated β-MHC mRNA levels to 24 ± 5, 21 ± 7, and 6 ± 2% of contracting cells, respectively. In contrast, these inhibitors of contraction upregulated α-MHC mRNA levels to 163 ± 19, 156 ± 7, and 198 ± 20% of contracting cells, respectively. Transient transfection with a rat β-MHC promoter-luciferase expression plasmid demonstrated that all inhibitors of contraction significantly decreased β-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 mRNA 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 II or other growth factors into the culture medium. Thus intrinsic mechanical signals rather than alterations in [Ca2+](i) regulate α-MHC and β-MHC gene expression by both transcriptional and posttranscriptional mechanisms.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume273
Issue number2 42-2
StatePublished - 1997
Externally publishedYes

Fingerprint

Myosin Heavy Chains
Gene expression
Rats
Gene Expression
Messenger RNA
Muscle Cells
Verapamil
RNA Stability
Dactinomycin
Luciferases
Angiotensin II
Transfection
Half-Life
Culture Media
Assays
Intercellular Signaling Peptides and Proteins
Plasmids
Down-Regulation

Keywords

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

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Myosin heavy chain gene expression in neonatal rat heart cells : Effects of [Ca2+](i) and contractile activity. / Qi, Ming; Puglisi, José L.; Byron, Kenneth L.; Ojamaa, Kaie; Klein, Irwin; Bers, Donald M; Samarel, Allen M.

In: American Journal of Physiology - Cell Physiology, Vol. 273, No. 2 42-2, 1997.

Research output: Contribution to journalArticle

Qi, Ming ; Puglisi, José L. ; Byron, Kenneth L. ; Ojamaa, Kaie ; Klein, Irwin ; Bers, Donald M ; Samarel, Allen M. / Myosin heavy chain gene expression in neonatal rat heart cells : Effects of [Ca2+](i) and contractile activity. In: American Journal of Physiology - Cell Physiology. 1997 ; Vol. 273, No. 2 42-2.
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