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Updated: Oct 5, 2026
Myo-mechanical Analysis of Isolated Skeletal Muscle
Published on: February 22, 2011
Impaired muscular contractile performance and adenine nucleotide handling in creatine kinase-deficient mice
M Gorselink1, M R Drost, W A Coumans
1Department of Physiology, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands.
Abstract:
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.
Insights
Creatine kinase (CK) deficiency impairs muscle contraction and ATP regeneration in mice. The adenylate kinase pathway cannot fully compensate for the lack of CK activity during repeated contractions.
Area of Science:
- Biochemistry
- Muscle Physiology
- Enzymology
Background:
- Creatine kinase (CK) is crucial for maintaining cellular energy homeostasis by regulating ATP/ADP concentrations.
- CK plays a vital role in energy metabolism within muscle cells.
- Understanding CK's function is key to comprehending muscle energetics.
Purpose of the Study:
- To investigate the functional consequences of lacking creatine kinase activity.
- To assess the impact of CK deficiency on muscle contractile performance.
- To determine the role of CK in ATP regeneration during muscle activity.
Main Methods:
- Studied contractile performance in CK knockout (CK(-/-)) mice and wild-type controls.
- Assessed maximal torque during single and repeated tetanic contractions of dorsal flexors.
- Measured muscular high-energy phosphate content (ATP, IMP) at rest, post-contraction, and during recovery.
Main Results:
- CK(-/-) mice exhibited significantly lower maximal torque in dorsal flexor muscles compared to wild-type mice.
- Reduced resting muscle ATP and elevated IMP levels were observed in CK(-/-) mice.
- ATP levels decreased significantly during repeated contractions in CK(-/-) mice, indicating impaired ATP regeneration.
Conclusions:
- The absence of CK activity leads to diminished muscle contractile force.
- The adenylate kinase pathway is insufficient to fully compensate for the lack of CK in ATP regeneration.
- CK deficiency results in reduced basal adenine nucleotide levels and impaired energy buffering in muscle.
