Contraction-induced changes in skeletal muscle Na plus ,K plus pump mRNA expression - importance of exercise intensity and Ca2+-mediated signalling

Aim: To investigate if exercise intensity and Ca2+ signalling regulate Na+,K+ pump mRNA expression in skeletal muscle. Methods: The importance of exercise intensity was evaluated by having trained and untrained humans perform intense intermittent and prolonged exercise. The importance of Ca2+ signalling was investigated by electrical stimulation of rat soleus and extensor digitorum longus (EDL) muscles in combination with studies of cell cultures. Results: Intermittent cycling exercise at similar to 85% of VO(2peak) increased (P < 0.05) alpha 1 and beta 1 mRNA expression similar to 2-fold in untrained and trained subjects. In trained subjects, intermittent exercise at similar to 70% of VO(2peak) resulted in a less (P < 0.05) pronounced increase (similar to 1.4-fold; P < 0.05) for alpha 1 and no change in beta 1 mRNA. Prolonged low intensity exercise increased (P < 0.05) mRNA expression of alpha 1 similar to 3.0-fold and alpha 2 similar to 1.8-fold in untrained but not in trained subjects. Electrical stimulation of rat soleus, but not EDL, muscle increased (P < 0.05) alpha 1 mRNA expression, but not when combined with KN62 and cyclosporin A incubation. Ionomycin incubation of cultured primary rat skeletal muscle cells increased (P < 0.05) alpha 1 and reduced (P < 0.001) alpha 2 mRNA expression and these responses were abolished (P < 0.05) by co-incubation with cyclosporin A or KN62. Conclusion: (1) Exercise-induced increases in Na+,K+ pump alpha 1 and beta 1 mRNA expression in trained subjects are more pronounced after high- than after moderate- and low-intensity exercise. (2) Both prolonged low and short-duration high-intensity exercise increase alpha 1 mRNA expression in untrained subjects. (3) Ca2+(i) regulates alpha 1 mRNA expression in oxidative muscles via Ca2+/calmodulin-dependent protein kinase (CaMK) and calcineurin signalling pathways.