Decreased ATP cost of isometric contractions in ATP-depleted rat fast-twitch muscle.
ATP was depleted to inosine 5'-monophosphate (IMP) in gastrocnemius muscles of anesthetized rats during two consecutive bouts of intermittent tetanic stimulation (each 1 Hz at 100 Hz, 100-ms duration, for 3 min) separated by 5 min. During a subsequent 75-min recovery period, resynthesis of adenine nucleotide from IMP was inhibited in one group of muscles with hadacidin (N-formyl-N-hydroxyaminoacetate, total dose 300 mg/kg ip), an inhibitor of adenylosuccinate synthase. In vivo 31P-nuclear magnetic resonance spectra and analysis of muscle extracts confirmed that ATP was reduced by over 30% in hadacidin-treated muscles compared both with nonstimulated muscles and with identically stimulated and rested control muscles in saline-injected rats. After the recovery period, calculated [ADP] in ATP-depleted muscles was half that in controls, while phosphorylation potential [PP = ln([ATP]/[ADP] [Pi]), where Pi is inorganic phosphate] and twitch force were similar. During a final 8 min of 0.75-Hz twitch stimulation, [ADP] and the initial rate of phosphocreatine (PCr) hydrolysis were less in ATP-depleted compared with control muscles, while changes in PP and twitch force were similar in the two groups. During a final 3 min of tetanic stimulation, ATP, PCr, and pH decreased less in ATP-depleted compared with control muscles. The results indicate that the ATP cost of isometric contraction is decreased by acute ATP depletion.
Foley
J M
JM
Department of Physiology, Michigan State University, East Lansing 48824.
Harkema
S J
SJ
Meyer
R A
RA
D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000378:metabolism*; D000818:Animals; D004558:Electric Stimulation; D004734:Energy Metabolism; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D007537:Isometric Contraction / Q000502:physiology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009132:Muscles / Q000378:metabolism* / Q000502:physiology; D010758:Phosphorus; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D010758:Phosphorus; D000255:Adenosine Triphosphate; C001321:hadacidin; D005998:Glycine