Skeletal muscle contractile performance and ADP accumulation in adenylate kinase-deficient mice

The production of AMP by adenylate kinase (AK) and subsequent deamination by AMP deaminase limits ADP accumulation during conditions of high-energy demand in skeletal muscle. The goal of this study was to investigate the consequences of AK deficiency (−/−) on adenine nucleotide management and whole muscle function at high-energy demands. To do this, we examined isometric tetanic contractile performance of the gastrocnemius-plantaris-soleus (GPS) muscle group in situ in AK1−/− mice and wild-type (WT) controls over a range of contraction frequencies (30–120 tetani/min). We found that AK1−/− muscle exhibited a diminished inosine 5′-monophosphate formation rate (14% of WT) and an inordinate accumulation of ADP (∼1.5 mM) at the highest energy demands, compared with WT controls. AK-deficient muscle exhibited similar initial contractile performance (521 ± 9 and 521 ± 10 g tension in WT and AK1−/− muscle, respectively), followed by a significant slowing of relaxation kinetics at the highest energy demands relativ...