Regulation and function of Ca2+-calmodulin-dependent protein kinase II of fast-twitch rat skeletal muscle.
The activation and function of Ca(2+)-calmodulin-dependent kinase II (CaMKII) in contracting rat skeletal muscle was examined. The increase in autonomous activity and phosphorylation at Thr(287) of CaMKII of gastrocnemius muscle in response to contractions in situ was rapid and transient, peaking at 1-3 min, but reversed after 30 min of contractions. There was a positive correlation between CaMKII phosphorylation at Thr(287) and autonomous CaMKII activity. In contrast to the rapid and transient increase in autonomous CaMKII activity, the phosphorylation of the putative CaMKII substrate trisk95/triadin was rapid and sustained during contractions. There were no changes in CaMKII activity and phosphorylation or trisk95 phosphorylation in the resting contralateral muscles during stimulation. When fast-twitch muscles were contracted ex vivo, CaMKII inhibition resulted in a greater magnitude of fatigue as well as blunted CaMKII and trisk95 phosphorylation, identifying trisk95 as a physiological CaMKII substrate. In summary, skeletal muscle CaMKII activation was rapid and sustained during exercise/contraction and is mediated by factors within the contracting muscle, probably through allosteric activation via Ca(2+)-CaM. CaMKII may signal through trisk95 to modulate Ca(2+) release in fast-twitch rat skeletal muscle during exercise/contraction.
Rose
Adam J
AJ
Copenhagen Muscle Research Centre, Department of Exercise and Sport Sciences, Section of Human Physiology, University of Copenhagen, Universitetsparken 13, Copenhagen, Denmark, 2100. arose@ifi.ku.dk
Alsted
Thomas J
TJ
Kobberø
J Bjarke
JB
Richter
Erik A
EA
D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000502:physiology*; D018763:Muscle Fatigue / Q000502:physiology; D018656:Muscle Fibers, Fast-Twitch / Q000201:enzymology* / Q000502:physiology; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000201:enzymology* / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D002352:Carrier Proteins; D009124:Muscle Proteins; D047428:Protein Kinase Inhibitors; C070048:triadin; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases