© 1993 by European Society of Cardiology
Copyright © 1993, European Society of Cardiology
Skinned cardiac fibres of diabetic rats: contractile activation and effects of 2,3-butanedione monoxime (BDM) and caffeine
Laboratoire de Physiologie Cellulaire, URA CNRS 1121, Bât 443, Université Paris-XI, 91405 Orsay Cédex, France: N Khandoudi, A C Guo, M Chesnais, D Feuvray.
Correspondence to Dr Feuvray.
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.
Cardiovascular Research 1993;27:447-452
KEYWORDS streptozotocin diabetes; skinned cardiac fibres; calcium sensitivity; 2,3-butanedione monoxime; caffeine
We wish to thank Dr Renée Ventura-Clapier for her helpful comments on an earlier version of the manuscript and Françoise James for her technical assistance. This work was supported by grants from the Institut National de la Santé et de la Recherche Médicale (INSERM) (CRE-910407) and from the Association Française contre les Myopathies.
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