An acute decrease in TCA cycle intermediates does not affect aerobic energy delivery in contracting rat skeletal muscle.
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 (SigmaTCAI) 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 SigmaTCAI 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.
Dawson
Kristen D
KD
Exercise Metabolism Research Group, Department of Kinesiology, McMaster University, Hamilton, ON, Canada L8S 4K1.
Baker
David J
DJ
Greenhaff
Paul L
PL
Gibala
Martin J
MJ
D000410:Alanine Transaminase / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D002952:Citric Acid Cycle / Q000502:physiology*; D004734:Energy Metabolism / Q000502:physiology*; D006003:Glycogen / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D009119:Muscle Contraction / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism*; D005082:Physical Exertion / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
D000596:Amino Acids; D006003:Glycogen; D000410:Alanine Transaminase