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 P-31-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][P(i)]), where P(i) 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.