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

• Published in: Acta Physiologica 2010-04, Vol.198 (4), p.487-498
• Main Authors: Nordsborg, N.B, Kusuhara, K, Hellsten, Y, Lyngby, S, Lundby, C, Madsen, K, Pilegaard, H
• Format: Article
• Language: English
• Subjects: adaptation; Biological and medical sciences; exercise; Fundamental and applied biological sciences. Psychology; human; humans; transcriptional regulation; Vertebrates: anatomy and physiology, studies on body, several organs or systems
• ISSN: 1748-1708; 1748-1716
• DOI: 10.1111/j.1748-1716.2009.02057.x

To investigate if exercise intensity and Ca²⁺ signalling regulate Na⁺,K⁺ pump mRNA expression in skeletal muscle. 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. Intermittent cycling exercise at ~85% of VO₂peak increased (P < 0.05) α1 and β1 mRNA expression ~2-fold in untrained and trained subjects. In trained subjects, intermittent exercise at ~70% of VO₂peak resulted in a less (P < 0.05) pronounced increase (~1.4-fold; P < 0.05) for α1 and no change in β1 mRNA. Prolonged low intensity exercise increased (P < 0.05) mRNA expression of α1 ~3.0-fold and α2 ~1.8-fold in untrained but not in trained subjects. Electrical stimulation of rat soleus, but not EDL, muscle increased (P < 0.05) α1 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) α1 and reduced (P < 0.001) α2 mRNA expression and these responses were abolished (P < 0.05) by co-incubation with cyclosporin A or KN62. (1) Exercise-induced increases in Na⁺,K⁺ pump α1 and β1 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 α1 mRNA expression in untrained subjects. (3) Ca²⁺i regulates α1 mRNA expression in oxidative muscles via Ca²⁺/calmodulin-dependent protein kinase (CaMK) and calcineurin signalling pathways.