CONTRACTILE AND METABOLIC EFFECTS OF INCREASED CREATINE-KINASE ACTIVITY IN MOUSE SKELETAL-MUSCLE

The effects of increased expression of creatine kinase (CK) in skeleta l muscle were studied in control and transgenic animals homozygous for expression of the B subunit of CK. CK activity was 47% higher in tran sgenic gastrocnemius muscle. The CK activity was distributed as follow s: 45 +/- 1% MM dimer, 31 +/- 4% MB dimer, and 22 +/- 5% BB dimer. No significant differences in metabolic or contractile proteins were dete cted except for a 22% decrease in lactate dehydrogenase activity and a 9% decrease in adenylate kinase activity. The only significant effect in contractile activity was that the rise time of a 5-s isometric con traction was 28% faster in the transgenic muscle. P-31 nuclear magneti c resonance (NMR) spectra were obtained from control and transgenic mu scles during mechanical activation, and there were no NMR measurable d ifferences detected. These results indicate that a 50% increase in CK activity due to expression of the B subunit does not have large effect s on skeletal muscle metabolism or contractile function. Therefore, co ntrol muscle has sufficient CK activity to keep up with changes in cel lular high-energy phosphates except during the early phase of intense contractile activity.