Ca/calmodulin-dependent protein kinase II affects contractile, but not fatigue-related phenotype in rat skeletal muscle

Calcium/calmodulin-dependent protein kinase II (CaMKII) is the main CaMK in skeletal muscle and its expression increases with endurance training. Because CaMKII has been implicated as a regulator of mitochondrial biogenesis and calcium handling, we investigated the effects of acute CaMKII overexpression in skeletal muscle in vivo. We overexpressed α/β-CaMKII in adult rat m. gastrocnemius (GM) and m. soleus (SOL) via gene electro-transfer. CaMKII overexpression did not alter cytochrome c oxidase IV (COXIV) protein levels in either GM or SOL. Likewise, mRNA levels of oxidative phosphorylation components COXIV, COXI and the transcriptional coactivator PGC-1α were not different between empty-and CaMKII-transfected m. soleus, whereas succinate dehydrogenase subunit b mRNA was decreased in CaMKII-transfected m. soleus (-26%, p<0.05). Force parameters of transfected muscles were measured in situ with intact innervations and perfusion. Strength and fatigue resistance of control-and CaMKII-transfected soleus and gastrocnemius did not differ. However, CaMKII overexpression decreased twitch time-to-peak force (p<0.05) and half-relaxation time (p<0.05). In addition, CaMKII-overexpressing m. soleus fibres displayed increased sarco/endoplasmic reticulum Ca 2+-ATPase 2 expression compared to non-transfected fibres (p<0.001). Our results suggest that CaMKII is not sufficient for mitochondrial biogenesis, but regulates the contractile muscle phenotype.