Murine muscles deficient in creatine kinase tolerate repeated series of high-intensity contractions

Murine muscles lacking both mitochondrial (Mi-CK) and cytoplasmic (MM-CK) c reatine kinase (CK-/-) show depressed mechanical performance in association with low muscle ATP and enhanced IMP content. The aims of the present stud y were to elucidate the possible role of low ATP and high IMP content in im pairment of mechanical performance in CK-/- mice and to establish whether C K-/- muscles are able to sustain repeated series of high-intensity contract ions. The dorsal flexors of CK-/- and control mice were subjected in situ t o two series of 12 tetanic contractions using a custom-made mouse isometric dynamometer. The muscle content of high-energy phosphates was analysed by HPLC. ATP content declined from 20.6 +/-1.9 to 15.5 +/-2.4 mu mol g(-1) dry weight (d.w.); IMP content increased from 1.2 +/-0.4 to 2.4 +/-1.1 mu mol g(-1) d.w. during the first contraction series in CK-/- muscle. Despite the se unfavourable changes, maximal torque developed during the first contract ion of either series did not differ, indicating that the altered content of ATP and IMP does not play a decisive role in impaired mechanical performan ce in CK-/- mice. The relative decline in torque during the two series did not differ in CK-/- (-20.4 +/-6.6 vs. -23.8 +/-9.9%). In contrast. wild-typ e (WT) muscles showed a significantly more pronounced decline during the se cond series (-12.3 +/-7.4 vs. -20.1 +/-6.8%). Muscle ATP and IMP content di d not change in CK-/-, whereas in WT IMP content increased significantly du ring the second contraction series. These findings indicate that CK-/- tole rate repeated series of high-intensity contractions better than WT, while i n CK-/- muscle an additional source of energy is mobilised to regenerate AT P during the second series.