TY - JOUR

T1 - Inactivity and exercise training differentially regulate the abundance of Na+, K+-ATPase in human skeletal muscle

AU - Wyckelsma, Victoria L

AU - Perry, Ben D

AU - Bangsbo, Jens

AU - McKenna, Michael John

N1 - CURIS 2019 NEXS 331

PY - 2019

Y1 - 2019

N2 - Physical inactivity is a global health risk that can be addressed through application of exercise training suitable for an individual's health and age. People's willingness to participate in physical activity is often limited by an initially poor physical capability and early onset of fatigue. One factor associated with muscle fatigue during intense contractions is an inexcitability of skeletal muscle cells, reflecting impaired transmembrane Na+/K+ exchange and membrane depolarisation, which are regulated via the transmembranous protein, Na+,K+-ATPase (NKA). This short review focuses on the plasticity of NKA in skeletal muscle in humans following periods of altered usage, exploring NKA upregulation with exercise training and downregulation with physical inactivity. In human skeletal muscle, the NKA content quantified by the [3H]ouabain binding site content shows robust, yet tightly constrained upregulation of 8-22% with physical training, across a broad range of exercise training types. Muscle NKA content in humans undergoes extensive downregulation with injury that involves substantial muscular inactivity. Surprisingly, however, no reduction in NKA content was found in the single study which investigated short-term disuse. Despite clear findings that exercise training and injury modulate NKA content, the adaptability of the individual NKA isoforms in muscle (α1-3 and β1-3) and of the accessory and regulatory protein FXYD1, are surprisingly inconsistent across studies, for exercise training, as well as for injury/disuse. Potential reasons for this are explored. Finally, we provide suggestions for future studies to provide greater understanding of NKA regulation during exercise training and inactivity in humans.

AB - Physical inactivity is a global health risk that can be addressed through application of exercise training suitable for an individual's health and age. People's willingness to participate in physical activity is often limited by an initially poor physical capability and early onset of fatigue. One factor associated with muscle fatigue during intense contractions is an inexcitability of skeletal muscle cells, reflecting impaired transmembrane Na+/K+ exchange and membrane depolarisation, which are regulated via the transmembranous protein, Na+,K+-ATPase (NKA). This short review focuses on the plasticity of NKA in skeletal muscle in humans following periods of altered usage, exploring NKA upregulation with exercise training and downregulation with physical inactivity. In human skeletal muscle, the NKA content quantified by the [3H]ouabain binding site content shows robust, yet tightly constrained upregulation of 8-22% with physical training, across a broad range of exercise training types. Muscle NKA content in humans undergoes extensive downregulation with injury that involves substantial muscular inactivity. Surprisingly, however, no reduction in NKA content was found in the single study which investigated short-term disuse. Despite clear findings that exercise training and injury modulate NKA content, the adaptability of the individual NKA isoforms in muscle (α1-3 and β1-3) and of the accessory and regulatory protein FXYD1, are surprisingly inconsistent across studies, for exercise training, as well as for injury/disuse. Potential reasons for this are explored. Finally, we provide suggestions for future studies to provide greater understanding of NKA regulation during exercise training and inactivity in humans.

KW - Faculty of Science

KW - Na+,K+ pump

KW - Physical activity

KW - Disuse

U2 - 10.1152/japplphysiol.01076.2018

DO - 10.1152/japplphysiol.01076.2018

M3 - Review

C2 - 31369327

VL - 127

SP - 905

EP - 920

JO - Journal of Applied Physiology

JF - Journal of Applied Physiology

SN - 8750-7587

IS - 4

ER -