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This Article Full Text Full Text (PDF) All Versions of this Article: 288/6/C1287    most recent 00567.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (10) Citing Articles via Google Scholar Google Scholar Articles by Hancock, C. R. Articles by Terjung, R. L. Search for Related Content PubMed PubMed Citation Articles by Hancock, C. R. Articles by Terjung, R. L.

MUSCLE CELL BIOLOGY AND CELL MOTILITY

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

¹Medical Pharmacology and Physiology, College of Medicine, University of Missouri-Columbia; ²Department of Cell Biology and Histology, University of Nijmegen, Nijmegen, The Netherlands; ³Department of Biomedical Sciences, College of Veterinary Medicine; and ⁴Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri

Submitted 23 November 2004 ; accepted in final form 13 January 2005

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 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.

AMP deaminase; tetanic contraction; muscle relaxation; calcium handling; cross-bridge cycling

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