title: Skeletal muscle contractile performance and ADP accumulation in adenylate kinase-deficient mice.
abstract: 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 ( approximately 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 relative to WT controls. This is consistent with a depressed capacity to sequester calcium in the presence of high ADP. However, the overall pattern of fatigue in AK1(-/-) mice was similar to WT control muscle. Our findings directly demonstrate the importance of AMP formation and subsequent deamination in limiting ADP accumulation. Whole muscle contractile performance was, however, remarkably tolerant of ADP accumulation markedly in excess of what normally occurs in skeletal muscle.
authors.affiliation: Medical Pharmacology and Physiology, College of Medicine, University of Missouri-Columbia, Columbia, MO 65211, USA.
authors.forename: Chad R
authors.initials: CR
authors.lastname: Hancock
authors.forename: Edwin
authors.initials: E
authors.lastname: Janssen
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Terjung
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism*; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000263:Adenylate Kinase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D051379:Mice; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000502:physiology*; D009126:Muscle Relaxation / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism / Q000502:physiology*; D010641:Phenotype; D013746:Tetany / Q000503:physiopathology
chemical_list: D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000263:Adenylate Kinase