APPS November 2002 Meeting Abstract 1109


Damian G. Anderson, Andrew D. Williams, Michael F. Carey, Alan Hayes, Exercise Metabolism Unit, Centre for Rehabilitation, Exercise and Sport Science, Victoria University, Vic.

Unlike histological and contractile changes, disturbances in the metabolism of dystrophic muscle have not been fully elucidated. Numerous studies have suggested limitations to oxidative metabolism, yet no studies have directly investigated the output of the mitochondria, ATP production. Therefore, we investigated the mitochondrial ATP production (MAPR) of dystrophin-deficient dystrophic (mdx) muscles. Normal (n=6) and mdx (n=8) mice were deeply anaesthetised with sodium pentobarbitone (60 mg/kg body weight i.p.) and the gastrocnemius muscles removed and separated into red (oxidative) and white (glycolytic) portions. The left gastrocnemius was used to measure MAPR immediately, while the right was snap frozen for later determination of ATP concentrations. Animals were then killed by overdose of anaesthetic. To measure MAPR, suspensions of intact mitochondria were added to cuvettes containing 40ÁM purified ADP, ATP monitoring reagent (FL-AAM; Sigma) and a variety of substrates representing carbohydrate, fat and protein metabolism. There were no differences in the MAPR of red gastrocnemius muscles from normal and dystrophic mice. In contrast, MAPR from dystrophic white gastrocnemius muscles was significantly higher (P<0.01) than normal muscles, most likely due to a transition from glycolytic to oxidative fibre types in dystrophic muscle. Despite no decrease in MAPR in dystrophic muscles, resting ATP levels were significantly lower (P<0.01) in both oxidative and glycolytic dystrophic gastrocnemius muscles. These results suggest that the ability of dystrophin-deficient mitochondria to produce ATP is not impaired per se. However, the lower ATP levels suggest that a) there is increased usage of ATP, even in resting muscles, most likely due to calcium buffering/removal mechanisms; and/or b) MAPR may be impaired in dystrophic muscles in vivo due to the presence of elevated calcium concentrations.

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