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. 2007 Sep 1;583(Pt 2):785-95.
doi: 10.1113/jphysiol.2007.138529. Epub 2007 Jul 12.

Effect of endurance exercise training on Ca2+ calmodulin-dependent protein kinase II expression and signalling in skeletal muscle of humans

Adam J Rose  1 , Christian Frøsig, Bente Kiens, Jørgen F P Wojtaszewski, Erik A Richter
Affiliations

Effect of endurance exercise training on Ca2+ calmodulin-dependent protein kinase II expression and signalling in skeletal muscle of humans

Adam J Rose et al. J Physiol. .

Abstract

Here the hypothesis that skeletal muscle Ca(2+)-calmodulin-dependent kinase II (CaMKII) expression and signalling would be modified by endurance training was tested. Eight healthy, young men completed 3 weeks of one-legged endurance exercise training with muscle samples taken from both legs before training and 15 h after the last exercise bout. Along with an approximately 40% increase in mitochondrial F(1)-ATP synthase expression, there was an approximately 1-fold increase in maximal CaMKII activity and CaMKII kinase isoform expression after training in the active leg only. Autonomous CaMKII activity and CaMKII autophosphorylation were increased to a similar extent. However, there was no change in alpha-CaMKII anchoring protein expression with training. Nor was there any change in expression or Thr(17) phosphorylation of the CaMKII substrate phospholamban with training. However, another CaMKII substrate, serum response factor (SRF), had an approximately 60% higher phosphorylation at Ser(103) after training, with no change in SRF expression. There were positive correlations between the increases in CaMKII expression and SRF phosphorylation as well as F(1)ATPase expression with training. After training, there was an increase in cyclic-AMP response element binding protein phosphorylation at Ser(133), but not expression, in muscle of both legs. Taken together, skeletal muscle CaMKII kinase isoform expression and SRF phosphorylation is higher with endurance-type exercise training, adaptations that are restricted to active muscle. This may contribute to greater Ca(2+) mediated regulation during exercise and the altered muscle phenotype with training.

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Figures

Figure 1
Figure 1. Representative immunoblots
Skeletal muscle samples from the vastus lateralis muscle of the passive (P) and active (A) leg before (Pre) and after (Post) 3 week of exercise training were extracted and lysates were immunoblotted for total and phosphorylated proteins as described in Methods. Isoforms of CaMKII as well as the relative electrophoretic mobility (Mr) of proteins are indicated. F1ATPase-β: β-subunit of F1-ATP synthase; αKAP: αCaMKII kinase anchoring protein; CaMKII: Ca2+–calmodulin-dependent protein kinase II; PLN: phospholamban; SRF: serum response factor; CREB: cAMP response element binding protein.
Figure 2
Figure 2. Endurance exercise training increases skeletal muscle F1ATPase-β expression
Skeletal muscle samples from the vastus lateralis muscle of the passive and active leg before (Pre) and after (Post) 3 weeks of exercise training were extracted and lysates were immunoblotted for β-subunit of F1-ATP synthase expression. Data are means ±s.e.m., n = 8; *different from Pre, P < 0.01; †different from Passive, P < 0.01.
Figure 3
Figure 3. Endurance exercise training increases skeletal muscle CaMKII kinase isoform expression and activity
Skeletal muscle samples from the vastus lateralis muscle of the passive and active leg before (Pre) and after (Post) 3 weeks of exercise training were extracted and lysates were immunoblotted for Ca2+–calmodulin-dependent protein kinase II expression (CaMKII; A and C) and phospho-Thr287CaMKII (B). Skeletal muscle extracts were assayed in vitro for Ca2+–calmodulin-dependent protein kinase II (CaMKII) activity in the presence (i.e. maximal activity; D) or absence (i.e. autonomous activity; middle panel; E) of Ca2+ and calmodulin. Shown in F are correlations between the changes in maximal CaMKII activity and CaMKII phosphorylation and activities of skeletal muscle of the active leg. Data are means ±s.e.m., n = 8; *different from Pre, P < 0.05; †different from Passive, P < 0.05.
Figure 4
Figure 4. Effects of endurance-type exercise on phosphorylation and expression of putative skeletal muscle CaMKII substrates
Skeletal muscle samples from the vastus lateralis muscle of the passive and active leg before (Pre) and after (Post) 3 week of exercise training were extracted and lysates were immunoblotted for phospholamban (PLN) expression (A) and Thr17 phosphorylation (B); serum response factor (SRF) expression (C) and Ser103 phosphorylation (D); and cAMP-response element binding protein (CREB) expression (E) and phospho-Ser133CREB (F). Data are mean ±s.e.m., n = 8; * different from Pre, P < 0.05; † different from Passive, P < 0.05.
Figure 5
Figure 5. Changes in CaMKII kinase isoform expression positively correlate with changes in SRF phosphorylation and F1ATPase-β expression with endurance exercise training
Shown are correlations between the changes in Ca2+–calmodulin-dependent kinase II (CaMKII) expression and serum response factor (SRF) Ser103 phosphorylation and mitochondrial F1-ATP synthase β-subunit expression of skeletal muscle of the active leg with endurance exercise training (A). Shown in B is a correlation between changes in SRF Ser103 phosphorylation and F1ATPase-β expression.
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