Fatigue resistance of rat extraocular muscles does not depend on creatine kinase activity.
BACKGROUND
Creatine kinase (CK) links phosphocreatine, an energy storage system, to cellular ATPases. CK activity serves as a temporal and spatial buffer for ATP content, particularly in fast-twitch skeletal muscles. The extraocular muscles are notoriously fast and active, suggesting the need for efficient ATP buffering. This study tested the hypotheses that (1) CK isoform expression and activity in rat extraocular muscles would be higher, and (2) the resistance of these muscles to fatigue would depend on CK activity.


RESULTS
We found that mRNA and protein levels for cytosolic and mitochondrial CK isoforms were lower in the extraocular muscles than in extensor digitorum longus (EDL). Total CK activity was correspondingly decreased in the extraocular muscles. Moreover, cytoskeletal components of the sarcomeric M line, where a fraction of CK activity is found, were downregulated in the extraocular muscles as was shown by immunocytochemistry and western blotting. CK inhibition significantly accelerated the development of fatigue in EDL muscle bundles, but had no major effect on the extraocular muscles. Searching for alternative ATP buffers that could compensate for the relative lack of CK in extraocular muscles, we determined that mRNAs for two adenylate kinase (AK) isoforms were expressed at higher levels in these muscles. Total AK activity was similar in EDL and extraocular muscles.


CONCLUSIONS
These data indicate that the characteristic fatigue resistance of the extraocular muscles does not depend on CK activity.
McMullen
Colleen A
CA
Department of Physiology, University of Kentucky, 800 Rose St., Lexington, KY 40536-0298, USA. colleen.mcmullen@uky.edu
Hayess
Katrin
K
Andrade
Francisco H
FH
D000263:Adenylate Kinase / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D003402:Creatine Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004139:Dinitrofluorobenzene / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D018763:Muscle Fatigue / Q000502:physiology*; D009801:Oculomotor Muscles / Q000201:enzymology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation
D004791:Enzyme Inhibitors; D007527:Isoenzymes; D004139:Dinitrofluorobenzene; D003402:Creatine Kinase; D000263:Adenylate Kinase