Abstract

The maintenance of transmembrane Na+ and K+ concentration gradients and membrane potential is vital for the production of force in skeletal muscle. In aging an inability to maintain ion regulation and membrane potential would have adverse consequences on the capacity for performing repeated muscle contractions, which are critical for everyday activities and functional independence. This short review focusses on the effects of aging on one major and vital component affecting muscle Na+ and K+ concentrations, membrane potential and excitability in skeletal muscle, the Na+,K+-ATPase (Na+,K+-pump, NKA) protein. The review examines the effects of age on NKA in both human and rodent models and highlights a distant lack of research in NKA with aging. In rodents, the muscle NKA measured by [3H]ouabain binding site content, declines with advanced age from peak values in early life. In human skeletal muscle, however, there appears to be no age effect on [3H]ouabain binding site content in physically active older adults between 55 and 76 years compared to those aged between 18 and 30 years of age. Analysis of the NKA isoforms reveal differential changes with age in fiber-types in both rat and humans. The data show considerable disparities, suggesting different regulation of NKA isoforms between rodents and humans. Finally we review the importance of physical activity on NKA content in older humans. Findings suggest that physical activity levels of an individual may have a greater effect on regulating the NKA content in skeletal muscle rather than aging per se, at least up until 80 years of age.

Highlights

  • Clinical Exercise Science Program, Institute of Sport Exercise and Active Living, Victoria University, Melbourne, VIC, Australia

  • A fundamental factor underpinning skeletal muscle contractile function is the maintenance of membrane excitability, which is heavily dependent on transmembrane sodium (Na+), potassium (K+), and chloride (Cl−) gradients and conductance’s via their effects on muscle membrane potential (Em) (Hodgkin and Horowicz, 1959)

  • This short review focusses on the effects of aging on one major component of ion regulation in skeletal muscle, the Na+,K+-ATPase (Na+,K+-pump, NKA) protein in skeletal muscle, which is vital for the regulation of transmembrane Na+ and K+ concentration gradients, Em and excitability in skeletal muscle cells (Clausen, 2003b)

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Summary

IMPLICATIONS OF IMPAIRED SKELETAL MUSCLE ION REGULATION IN AGING

A fundamental factor underpinning skeletal muscle contractile function is the maintenance of membrane excitability, which is heavily dependent on transmembrane sodium (Na+), potassium (K+), and chloride (Cl−) gradients and conductance’s via their effects on muscle membrane potential (Em) (Hodgkin and Horowicz, 1959). This suggested that an age associated reduction in muscle NKA content in humans might only be apparent at more advanced ages To investigate this possible age effect on NKA content further, we analyzed all of the [3H]ouabain binding site content data in aging-related research collected in healthy, older participants in our laboratory over the past 4 years (McKenna et al, 2012; Perry et al, 2013; Wyckelsma et al, 2016). Older participants in one of the studies reported similar physical activity levels to the healthy young controls, despite the intensities of activities likely differing considerably between the groups (Wyckelsma et al, 2016) This may suggest that preserving some level of physical activity might be the important factor in the maintenance of skeletal muscle NKA with age in humans. Since we have no analyses of muscle [3H]ouabain binding in healthy adults greater than 80 years, we cannot exclude the possibility that a decline may occur beyond this age

AGE ASSOCIATED ALTERATIONS TO NKA ISOFORMS
VL Type II fibers
Findings
CHRONIC REGULATION OF NKA WITH EXERCISE TRAINING IN THE AGED
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