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Changes in crossbridge mechanical properties in diabetic rat cardiomyopathy

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Abstract

Diabetes mellitus is associated with an increased risk of heart failure, resulting from a specific cardiomyopathy independent of coronary atherosclerosis. It is not yet established whether altered myocardial function is related to changes in molecular mechanics of myosin. Accordingly, we investigated the total number, single force and kinetics of myosin crossbridges (CB) in a rat model of streptozotocin–induced diabetic cardiomyopathy. Experiments were conducted on left ventricular papillary muscles from male diabetic (D) Wistar (n = 16) and age–matched control (C) rats (n = 15). Mechanical indices including the maximum unloaded shortening velocity Vmax and the maximum total isometric tension normalized per cross–sectional area TFmax were determined. Using A. F. Huxley’s equations, we calculated the total cycling CB number per mm2 Ψ, the elementary force per single CB Π, the maximum values of the rate constant for CB attachment f1 and detachment g1 and g2, and the turnover rate of myosin ATPase per site kcat. The D rats exhibited a 25% decrease in TFmax and a 34% decrease in Vmax as compared to C. This contractile dysfunction was associated with a significant reduction in Ψ (9.0 ± 1.6 in D versus 11.4 ± 1.9 109mm–2 in C, P < 0.001) without significant change in Π (6.1 ± 0.8 in D versus 6.3 ± 0.9 pN in C, NS). In the 2 groups, TFmax correlated positively with Ψ (r = 0.76, P < 0.001 and r = 0.64, P < 0.01, in D and C respectively) but no relationship was found between TFmax and Π. As compared to C, D showed lower values of f1, g1 and g2, and a slower turnover rate of myosin ATPase. Thus, present data suggested that the cardiac contractile impairment observed in streptozotocin–induced diabetic rat cardiomyopathy was mainly related to a decrease in active CB total number and CB kinetics alterations without significant change in CB single force.

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Authors and Affiliations

  1. Service de Cardiologie, Hôpital Ambroise Paré, 9 avenue Charles de Gaulle, 92104, Boulogne Cedex, France

    Th. Joseph & O. Dubourg

  2. Institut National de la Santé et de la Recherche Médicale U572 Hôpital Lariboisiére, 75010, Paris, France

    Th. Joseph, C. Coirault & Y. Lecarpentier

  3. Service d’Explorations Fonctionnelles, Cardio-Respiratoires Hôpital Bicêtre, 92475, Kremlin Bicêtre, France

    Y. Lecarpentier

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  1. Th. Joseph
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  2. C. Coirault
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  4. Y. Lecarpentier
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Correspondence to Th. Joseph.

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Joseph, T., Coirault, C., Dubourg, O. et al. Changes in crossbridge mechanical properties in diabetic rat cardiomyopathy. Basic Res Cardiol 100, 231–239 (2005). https://doi.org/10.1007/s00395-005-0512-5

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  • DOI: https://doi.org/10.1007/s00395-005-0512-5

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