Skinned cardiac fibres of diabetic rats: contractile activation and effects of 2,3-butanedione monoxime (BDM) and caffeine.

ABSTRACT

OBJECTIVE: The aim was to examine contractile properties of skinned cardiac fibres from rats with streptozotocin induced diabetes and to compare the effects of two agents, caffeine and 2,3-butanedione monoxime (BDM), on myocardial contractile characteristics of normal and diabetic cardiac fibres. METHODS: Small fibre bundles dissected from papillary muscles of the left ventricle were chemically skinned by exposure to Triton X-100. The tension-pCa (pCa = -log10 [Ca2+]) relationships were determined under isometric conditions. RESULTS: In skinned fibres from diabetic rats maximum Ca2+ activated force was unchanged in comparison with normal rats, but a significant, though small, increase in the Ca2+ sensitivity [pCa for one half maximal activation (pCa50)] of contraction was shown. Caffeine (5-20 mM) increased Ca2+ sensitivity in a dose dependent manner and to the same extent in the two groups of preparations. Up to 10 mM caffeine, maximum force was not affected. On the other hand, BDM (2 and 5 mM) decreased Ca2+ sensitivity in both normal and diabetic fibres, but the rightward shift of the tension-pCa relationship induced by BDM was more pronounced in diabetic than in normal fibres pCa50 was 5.55(SEM 0.02), 5.51(0.01), and 5.46(0.01) in normal fibres, and 5.62(0.01), 5.51(0.02), and 5.45(0.02) in diabetic fibres for 0, 2, and 5 mM BDM, respectively. Maximum tension was similarly decreased by BDM in the two groups of fibres. CONCLUSIONS: (1) No change is induced by diabetes in the site of action of caffeine; (2) some drugs that affect myofilament Ca2+ sensitivity, such as BDM, may act differently in diabetic and control myocardium.