Effects of chronic diabetes mellitus on the electrical and contractile activities, 45Ca2+ transport, fatty acid profiles and ultrastructure of isolated rat ventricular myocytes.

The effects of chronic experimental diabetes on electrophysiological properties, contractile behavior, 45Ca2+ transport, fatty acid profiles and ultrastructural characteristics were studied in enzymatically dissociated ventricular myocytes. Diabetes was induced in rats by streptozotocin administration and animals were killed 8-10 weeks later. Myocytes from diabetic rats exhibited electrical behavior similar to that of myocytes from control rats, but their contractile properties were altered. Their sensitivity of the twitch contractions to various positive and negative inotropic agents (isoproterenol, norepinephrine, phenylephrine, acetylcholine, ouabain and veratridine) was greatly diminished. However, a part of the contractile response (the tonic, sustained contractions) were increased in the diabetic myocytes, indicating that the changes are not caused by a decreased sensitivity of myofilaments. Furthermore, the diabetic myocytes exhibited also significant decrease in total Ca2+ content. The fatty acid profile in the diabetic group was changed mainly in that there were slightly elevated levels of docosahexaenoic acid and diminished levels of palmitic acid. The ultrastructure of the diabetic myocytes was affected only slightly. These investigations offer for the first time a comprehensive picture of changes related to diabetic cardiomyopathy as they occur at the level of cardiomyocytes.