Regulation and function of Ca2+–calmodulin-dependent protein kinase II of fast-twitch rat skeletal muscle

The activation and function of Ca²⁺–calmodulin-dependent kinase II (CaMKII) in contracting rat skeletal muscle was examined. The increase in autonomous activity and phosphorylation at Thr²⁸⁷ 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 Thr²⁸⁷ 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 Ca²⁺–CaM. CaMKII may signal through trisk95 to modulate Ca²⁺ release in fast-twitch rat skeletal muscle during exercise/contraction.