A cellular mechanism for impaired posthypoxic relaxation in isolated cardiac myocytes: Altered myofilament relaxation kinetics at reoxygenation

H. S. Silverman, M. Ninomiya, P. S. Blank, O. Hano, H. Miyata, H. A. Spurgeon, E. G. Lakatta, M. D. Stern

Research output: Contribution to journalArticlepeer-review

Abstract

Single, isolated rat ventricular myocytes were made hypoxic for 10 minutes and then reoxygenated. During hypoxia, there was a marked abbreviation of the mechanical twitch, without a decrease in its amplitude. Immediately after reoxygenation, both the time to peak shortening and the duration of relaxation were markedly prolonged, and they remained prolonged for 10-50 minutes. The alterations in contraction and relaxation were not associated with any change in the time course of either the transmembrane action potential or the cytosolic calcium transient, as recorded with the fluorescent probe indo 1. Intracellular pH, measured with a fluorescent probe (carboxyseminaphthorhodofluor), showed an acid shift during hypoxia and an alkaline rebound immediately after reoxygenation. The time courses of intracellular pH and contraction duration were not parallel during hypoxia or reoxygenation, and simulation of the alkaline pH shift by lowering PCO2 or superfusing NH4Cl (in the absence of exposure to hypoxia) did not quantitatively reproduce the prolongation of relaxation seen after reoxygenation. The prolongation of contraction after reoxygenation could be overridden by the β-adrenergic agonist isoproterenol or the nonenzymatic phosphatase butanedione monoxime. We conclude that delayed relaxation after reoxygenation exists at the single cell level and is due to an alteration of the properties of the myofilaments. Intracellular pH is not the primary mediator of this alteration. We speculate that alteration of intracellular inorganic phosphate or covalent modification of the myofilaments might be involved.

Original languageEnglish (US)
Pages (from-to)196-208
Number of pages13
JournalCirculation research
Volume69
Issue number1
DOIs
StatePublished - 1991

Keywords

  • Calcium
  • Hypoxia
  • Myocytes
  • Myofilaments
  • Relaxation

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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