Altered myocardial response to ouabain in diabetic rats: Mechanics and electrophysiology

Frederick S. Fein, Ronald S. Aronson, Charles W. Nordin, Betty Miller-Green, Edmund H. Sonnenblick

Research output: Contribution to journalArticle

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Abstract

Diabetes induced by streptozotocin in rats is associated with changes in the mechanical function of isolated ventricular papillary muscle. Relaxation is slowed and shortening velocity is depressed. The effects of ouabain (10-7 to 2 × 10-4 m) and changes in extracellular calcium ([Ca2+]0 = 0.6 to 12 mm) on the mechanical and electrical properties of normal and diabetic papillary muscles were studied. High doses of ouabain caused a rise in resting tension and a fall in developed tension in both diabetic and control muscles. However, these changes were strikingly greater in diabetic muscles which developed partial contractures at 10-4 m. The altered response to ouabain was observed in chronically (5 to 7 weeks or 3 months) but not acutely (less than 1 week) diabetic animals. Similarly, the response to ouabain was restored to normal after chronic (5 weeks) therapy with insulin but not after acute (4 days) therapy. In both normal and diabetic muscles, the mechanical effects of increasing [Ca2+]0 from 2.4 to 12.0 mm were qualitatively similar to those seen with ouabain at 10-5 to 10-4 m. Electrophysiologic studies showed that under control conditions action potentials of diabetic muscles were significantly longer than those of normal muscles. Treatment with progressively higher concentrations of ouabain (10-7 to 10-4 m) and [Ca2+]0 (2.4 to 12.0 mm) caused shortening of both normal and diabetic action potentials, but the effects of these interventions were much greater in the diabetics. These results suggest that the response of diabetic muscles to ouabain is markedly different from normal and that this altered response may be due to impaired regulation of intracellular Ca2+ levels in diabetic myocardium.

Original languageEnglish (US)
Pages (from-to)769-784
Number of pages16
JournalJournal of Molecular and Cellular Cardiology
Volume15
Issue number11
DOIs
StatePublished - 1983

Fingerprint

Electrophysiology
Ouabain
Mechanics
Muscles
Papillary Muscles
Action Potentials
Experimental Diabetes Mellitus
Ventricular Function
Contracture
Myocardium
Insulin
Calcium
Therapeutics

Keywords

  • Action potential duration
  • Calcium overload
  • Diabetes
  • Digitalis
  • Electrophysiology
  • Mechanics
  • Ouabain

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

Altered myocardial response to ouabain in diabetic rats : Mechanics and electrophysiology. / Fein, Frederick S.; Aronson, Ronald S.; Nordin, Charles W.; Miller-Green, Betty; Sonnenblick, Edmund H.

In: Journal of Molecular and Cellular Cardiology, Vol. 15, No. 11, 1983, p. 769-784.

Research output: Contribution to journalArticle

Fein, Frederick S. ; Aronson, Ronald S. ; Nordin, Charles W. ; Miller-Green, Betty ; Sonnenblick, Edmund H. / Altered myocardial response to ouabain in diabetic rats : Mechanics and electrophysiology. In: Journal of Molecular and Cellular Cardiology. 1983 ; Vol. 15, No. 11. pp. 769-784.
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N2 - Diabetes induced by streptozotocin in rats is associated with changes in the mechanical function of isolated ventricular papillary muscle. Relaxation is slowed and shortening velocity is depressed. The effects of ouabain (10-7 to 2 × 10-4 m) and changes in extracellular calcium ([Ca2+]0 = 0.6 to 12 mm) on the mechanical and electrical properties of normal and diabetic papillary muscles were studied. High doses of ouabain caused a rise in resting tension and a fall in developed tension in both diabetic and control muscles. However, these changes were strikingly greater in diabetic muscles which developed partial contractures at 10-4 m. The altered response to ouabain was observed in chronically (5 to 7 weeks or 3 months) but not acutely (less than 1 week) diabetic animals. Similarly, the response to ouabain was restored to normal after chronic (5 weeks) therapy with insulin but not after acute (4 days) therapy. In both normal and diabetic muscles, the mechanical effects of increasing [Ca2+]0 from 2.4 to 12.0 mm were qualitatively similar to those seen with ouabain at 10-5 to 10-4 m. Electrophysiologic studies showed that under control conditions action potentials of diabetic muscles were significantly longer than those of normal muscles. Treatment with progressively higher concentrations of ouabain (10-7 to 10-4 m) and [Ca2+]0 (2.4 to 12.0 mm) caused shortening of both normal and diabetic action potentials, but the effects of these interventions were much greater in the diabetics. These results suggest that the response of diabetic muscles to ouabain is markedly different from normal and that this altered response may be due to impaired regulation of intracellular Ca2+ levels in diabetic myocardium.

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