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

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 x 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.