Compensatory downregulation of myocardial Ca channel in SR from dogs with heart failure

C. R. Cory, L. J. McCutcheon, M. O'Grady, A. W. Pang, Jonathan Geiger, P. J. O'Brien

Research output: Contribution to journalArticle

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Abstract

In this study we tested the hypothesis that the ryanodine-binding Ca- release channel activity and density of the sarcoplasmic reticulum (SR) terminal cisternae were decreased in congestive heart failure (CHF) that occurs spontaneously in doberman pinschers or experimentally with rapid ventricular pacing of mongrels. We used a novel, sensitive, and easy-to- perform microassay and demonstrated a 50% decrease in activity of the myocardial SR Ca pump and a 75% reduction in SR Ca-release channel activity in CHF. Decreases in Ca channel content were associated with increases in net Ca sequestration. 45 Ca-release experiments from passively loaded SR terminal cisternae and ryanodine-binding studies confirmed a 53-68% downregulation of the Ca-release channel activity. As a consequence of release channel downregulation, there was partial restoration of net Ca sequestration activity in dogs with CHF and complete compensation in dogs with mild cardiac dysfunction. Deterioration of Ca cycling correlated with deterioration of myocardial performance, apparently due to decreased Ca- adenosinetriphosphate (ATPase) pump and not Ca channel content. One-half the reduction in Ca-release activity could be attributed to decreased Ca sequestration and one-half to decreased Ca channel density. Downregulation of Ca channel content decreases the amplitude of the Ca cycle and maximizes the downregulation of Ca pumps that may occur. Although these adaptations may reduce cellular energy expenditure, they are likely to render the myocardium more susceptible to fatigue and failure.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume264
Issue number3 33-3
StatePublished - Apr 20 1993

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Sarcoplasmic Reticulum
Down-Regulation
Heart Failure
Dogs
Ryanodine
Energy Metabolism
Fatigue
Adenosine Triphosphatases
Myocardium

Keywords

  • calcium channel
  • indo-1
  • myocardium
  • ryanodine

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Compensatory downregulation of myocardial Ca channel in SR from dogs with heart failure. / Cory, C. R.; McCutcheon, L. J.; O'Grady, M.; Pang, A. W.; Geiger, Jonathan; O'Brien, P. J.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 264, No. 3 33-3, 20.04.1993.

Research output: Contribution to journalArticle

Cory, C. R. ; McCutcheon, L. J. ; O'Grady, M. ; Pang, A. W. ; Geiger, Jonathan ; O'Brien, P. J. / Compensatory downregulation of myocardial Ca channel in SR from dogs with heart failure. In: American Journal of Physiology - Heart and Circulatory Physiology. 1993 ; Vol. 264, No. 3 33-3.
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