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This Article Full Text Full Text (PDF) All Versions of this Article: 565/2/637    most recent jphysiol.2004.079939v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dawson, K. D. Articles by Gibala, M. J. Search for Related Content PubMed PubMed Citation Articles by Dawson, K. D. Articles by Gibala, M. J.

¹ Exercise Metabolism Research Group, Department of Kinesiology, McMaster University, Hamilton, Ontario, L8S 4K1, Canada
² Centre for Integrated Systems Biology and Medicine, School of Biomedical Sciences, University of Nottingham, Nottingham NG7 2UH, UK

We tested the hypothesis that an acute decrease in muscle TCA cycle intermediates during contraction would compromise aerobic energy delivery. Male Wistar rats were anaesthetized and the gastrocnemius–plantaris–soleus (GPS) muscle complex from one leg was isolated and perfused with a red cell medium containing either saline (Con) or cycloserine (Cyclo; 0.05 mg g^–1), an inhibitor of alanine aminotransferase (AAT). After 1 h of perfusion, the GPS muscle was either snap frozen (Con-Rest, n = 11; Cyclo-Rest, n = 9) or stimulated to contract for 10 min (1 Hz, 0.3 ms, 2 V) with blood flow fixed at 30 ml min^–1 (100 g)^–1 and then snap frozen (Con-Stim, n = 10; Cyclo-Stim, n = 10). Maximal AAT activity was > 80% lower (P < 0.001) in both Cyclo-treated groups (Rest: 0.61 ± 0.02; Stim: 0.63 ± 0.01 mmol (kg wet wt)^–1 min^–1; mean ± S.E.M.) compared to Con (Rest: 3.56 ± 0.16; Stim: 3.92 ± 0.29). The sum of five measured TCAI (TCAI) was reduced by 23% in Cyclo-Rest versus Con-Rest but this was not different (P = 0.08). However, after 10 min of contraction, the TCAI was 25% lower (P = 0.006) in Cyclo-Stim compared to Con-Stim (1.88 ± 0.15 versus 2.48 ± 0.11 mmol (kg dry wt)^–1). Despite the acute decrease in TCAI after Cyclo treatment, the contraction-induced changes in markers of non-oxidative energy provision (phosphocreatine, ATP and lactate) and the decline in tension after 10 min of stimulation were similar compared to Con. These data do not support the hypothesis that the total muscle concentration of TCAI is causally linked to the rate of mitochondrial respiration during contraction.

(Received 23 November 2004; accepted after revision 30 March 2005; first published online 31 March 2005)
Corresponding author M. J. Gibala: Exercise Metabolism Research Group, Department of Kinesiology, McMaster University, Hamilton, ON, Canada L8S 4K1. Email: gibalam{at}mcmaster.ca

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