Impaired muscular contractile performance and adenine nucleotide handling in creatine kinase-deficient mice.

M. Gorselink, W.A. Bemelman, G.P.J. van Kranenburg, R.P. Hesselink, G.J. van der Vusse

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Abstract

Am J Physiol Endocrinol Metab 2001 Sep;281(3):E619-25 Related Articles, Books, LinkOut


Impaired muscular contractile performance and adenine nucleotide handling in creatine kinase-deficient mice.

Gorselink M, Drost MR, Coumans WA, van Kranenburg GP, Hesselink RP, van der Vusse GJ.

Department of Physiology, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands.

Creatine kinase (CK) forms a small family of isoenzymes playing an important role in maintaining the concentration of ATP and ADP in muscle cells. To delineate the impact of a lack of CK activity, we studied contractile performance during a single maximal tetanic contraction and during 12 repeated tetanic contractions of intact dorsal flexors of CK knockout (CK(-/-)) mice. To investigate the effect on ATP regeneration, muscular high-energy phosphate content was determined at rest, immediately after the contraction series, and after a 60-s recovery period. Maximal torque of the dorsal flexors was significantly lower in CK(-/-) mice than in wild-type animals, i.e., 23.7 +/- 5.1 and 33.3 +/- 6.8 mN. m. g(-1) wet wt, respectively. Lower muscle ATP (20.1 +/- 1.4 in CK(-/-) vs. 28.0 +/- 2.1 micromol/g dry wt in controls) and higher IMP (1.2 +/- 0.5 in CK(-/-) vs. 0.3 +/- 0.1 micromol/g dry wt in controls) levels at the onset of contraction may contribute to the declined contractility in CK(-/-) mice. In contrast to wild-type muscles, ATP levels could not be maintained during the series of 12 tetanic contractions of dorsal flexors of CK(-/-) mice and dropped to 15.5 +/- 2.4 micromol/g dry wt. The significant increase in tissue IMP (2.4 +/- 1.1 micromol/g dry wt) content after the contraction series indicates that ATP regeneration through adenylate kinase was not capable of fully compensating for the lack of CK. ATP regeneration via the adenylate kinase pathway is a likely cause of reduced basal adenine nucleotide levels in CK(-/-) mice.

Original languageEnglish
Pages (from-to)E619-E625
Number of pages7
JournalAmerican Journal of Physiology : Endocrinology and Metabolism
Volume281
Issue number3
DOIs
Publication statusPublished - 1 Jan 2001

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