O7-5 Muscle carnitine deficiency in pathogenesis of myopathy and cardiomyopathy of Duchenne muscular dystrophy (DMD)

Abstract

Objective: To determine tissue Carnitine (Cn) levels in the C57BL/10ScSn-Dmdmdx male mouse, murine model of DMD. Background:Muscle and cardiacmetabolism and function are dependent on the oxidation of fatty acids and glucose for ATP production, for which Cn serves as an essential cofactor. Skeletal muscle contains >90% of total body Cn stores and uptake across the muscle plasma membrane occurs against a 50 to 70 fold concentration gradient, mediated by the plasmalemmal Cn transporter, OCTN2. Muscle Cn deficiency and reduced long-chain fatty acid oxidation (FAO) have been reported in DMD muscle. We speculate that dystrophin deficiency in DMD, which causes disruption of the plasma membrane, likely disrupts OCTN2, leading to significant secondary tissue Cn depletion. Methods:We determined tissue Cn concentrations according to Cederblad and Lindstedt (1972) in the skeletal muscle (gluteus/quadriceps), diaphragm and ventricles of mdx mice (n = 10) compared to normal male controls: C57BL/6 (n=6), C3H (n=12) and C57BL/10 (n=10) mice. Results: Comparison of the mean Cn concentrations (± standard error mean) in mmol/g dry weight of muscle of the controls vs mdx mice is shown in the table.