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J Physiol Volume 574, Number 3, 889-903, August 1, 2006 DOI: 10.1113/jphysiol.2006.111757
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SKELETAL MUSCLE AND EXERCISE

Ca2+–calmodulin-dependent protein kinase expression and signalling in skeletal muscle during exercise

Adam J. Rose1, Bente Kiens1 and Erik A. Richter1

1 Copenhagen Muscle Research Centre, Department of Human Physiology, Institute of Exercise and Sport Sciences, University of Copenhagen, Universitetsparken 13, Copenhagen, Denmark, 2100

Ca2+ signalling is proposed to play an important role in skeletal muscle function during exercise. Here, we examined the expression of multifunctional Ca2+–calmodulin-dependent protein kinases (CaMK) in human skeletal muscle and show that CaMKII and CaMKK, but not CaMKI or CaMKIV, are expressed. Furthermore, the effect of exercise duration and intensity on skeletal muscle CaMKII activity and phosphorylation of downstream targets was examined. Eight healthy men exercised at ~67% of peak pulmonary O2 uptake Formula with muscle samples taken at rest and after 1, 10, 30, 60 and 90 min of exercise. Ten other men exercised for three consecutive 10 min bouts at 35%, 60% and 85% Formula with muscle samples taken at rest, at the end of each interval and 30 min post-exercise. There was a rapid and transient increase in autonomous CaMKII activity and CaMKII phosphorylation at Thr287 in skeletal muscle during exercise. Furthermore, the phosphorylation of phospholamban (PLN) at Thr17, which was identified as a CaMKII substrate in skeletal muscle, was rapidly (< 1 min) increased by exercise, and remained phosphorylated 5-fold above basal level during 90 min of exercise. The phosphorylation of serum response factor at Ser103, a putative CaMKII substrate, was higher after 30 min of exercise. PLN phosphorylation at Thr17 was higher with increasing exercise intensities. These data indicate that CaMKII is the major multifunctional CaMK in skeletal muscle and its activation occurs rapidly and is sustained during continuous exercise, with the activation being greater during intense exercise.

(Received 18 April 2006; accepted after revision 10 May 2006; first published online 11 May 2006)
Corresponding author A. J. Rose: Copenhagen Muscle Research Centre, Department of Human Physiology, Institute of Exercise and Sport Sciences, University of Copenhagen, Universitetsparken 13, Copenhagen, Denmark, 2100. Email: arose{at}ifi.ku.dk




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