Molecular regulation of cardiac myocyte adaptations to chronic hypoxia

Keith A Webster, Nanette Bishopric

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

The effects of chronic hypoxia on isolated neonatal rat cardiac myocytes were investigated in a model system of myocardial hypoxia. Spontaneously beating myocardiocytes were cultured for up to one week inside an environmental chamber at an oxygen tension of between 4 and 8 mmHg. In order to simulate a chronic reduced flow condition fresh hypoxic culture medium was replenished frequently to eliminate or minimize contributions of extracellular metabolite build-up, pH changes, or energy depletion. Under these conditions contractions became progressively impaired and irregular compared with aerobic cultures and beating frequency decreased to about 50% of control over 3 days. Reduced contractility was paralleled by a progressive decrease in the basal intracellular level of cAMP. Both of these effects could be reversed by introducing isoproterenol. Visualization of calcium fluxes using the fluorescent calcium chelator Indo-1 demonstrated that the slower contractions were associated with a pronounced decrease in the rate of calcium efflux during muscle relaxation. Changes in the expression of cAMP dependent genes was apparent in the hypoxic cells and the chronic administration of cAMP elevating drugs was toxic specifically to cells under hypoxia. We propose that cAMP may regulate some short and long-term adaptations of cardiac myocytes to chronic hypoxia.

Original languageEnglish
Pages (from-to)741-751
Number of pages11
JournalJournal of Molecular and Cellular Cardiology
Volume24
Issue number7
DOIs
StatePublished - Jan 1 1992
Externally publishedYes

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Cardiac Myocytes
Calcium
Cell Hypoxia
Muscle Relaxation
Poisons
Isoproterenol
Culture Media
Oxygen
Pharmaceutical Preparations
Genes
Hypoxia

Keywords

  • cAMP
  • Cardiac myocyte
  • Hypoxia

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

Molecular regulation of cardiac myocyte adaptations to chronic hypoxia. / Webster, Keith A; Bishopric, Nanette.

In: Journal of Molecular and Cellular Cardiology, Vol. 24, No. 7, 01.01.1992, p. 741-751.

Research output: Contribution to journalArticle

Webster, Keith A ; Bishopric, Nanette. / Molecular regulation of cardiac myocyte adaptations to chronic hypoxia. In: Journal of Molecular and Cellular Cardiology. 1992 ; Vol. 24, No. 7. pp. 741-751.
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