The effect of increased creatine kinase activity on contractile function and metabolism in mouse skeletal muscle. Roman, Brian B., Jeanne M. Foley, Ron A. Meyer, and Alan P. Koretsky. Department of Biological Sciences and Pittsburgh NMR Center for Biomedical Research, Carnegie Mellon University, Pittsburgh, PA 15213 and Department of Physical Education and Exercise Science, Departments of Physiology and Radiology, Michigan State University, East Lansing, MI
APStracts 2:0391C, 1995.
The effects of increased expression of creatine kinase (CK) in skeletal muscle were studied in normal and transgenic animals homozygous for expression of the B subunit of CK. CK activity measured at 37 C was elevated in gastrocnemius muscle extracts by 47% from 7980 +/- 280 [mu]moles min-1 gm-1 in control muscle to 11620 +/- 363 [mu]moles min-1 gm-1 in transgenic muscle. The CK activity was distributed among CK isoforms as 45% +/- 1 MM dimer, 31 +/- 4% MB dimer, and 22 +/- 5% BB dimer. Glycogen content, lactate dehydrogenase, phosphofructokinase, citrate synthase, adenylate kinase activities, and myosin heavy chain isoforms were compared in transgenic and normal muscle. No significant differences in any of these markers were detected except for a 22% decrease in lactate dehydrogenase activity in transgenic muscles (350 +/- 33 [mu]mol/min/g wet wt) compared to control (450 +/- 46 [mu]mol/min/g wet wt) and an 9% decrease in adenylate kinase activity in transgenic muscles (1230 +/- 92 [mu]mol/min/g wet wt) compared to control (1340 +/- 94 [mu]mol/min/g wet wt). In situ contractile information was obtained during isometric twitch, short and long tetanic stimulation of gastrocnemius-plantaris-soleus (GPS) muscle complex. There were no significant differences in the mechanical performance due to the alteration in the CK expression and activity except that the rise time of a 5 second isometric contraction was 28% faster in the transgenic animals (130 +/- 31 msec) than in normal animals (170 +/- 40 msec). 31P NMR spectra were obtained from GPS muscles from normal and transgenic muscles prior to, right after, and during recovery from a 1 sec isometric contraction. There were no differences in resting levels of Pi, phosphocreatine, ATP, and pH nor was there a difference in changes in these values due to contraction or during recovery from contraction. These results indicate that a 50% increase in CK activity due to expression of the B subunit does not have large effects on skeletal muscle metabolism or contractile function. Therefore, it is concluded that normal muscle has sufficient creatine kinase activity to keep up with changes in cellular high energy phosphates except during the early phase of intense contractile activity. 

Received 18 May 1995; accepted in final form 24 October 1995.
APS Manuscript Number C274-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 November 95