High-Intensity Training Represses FXYD5 and Glycosylates Na,K-ATPase in Type II Muscle Fibres, Which Are Linked with Improved Muscle K+ Handling and Performance

Abstract

Na+/K+ ATPase (NKA) comprises several subunits to provide isozyme heterogeneity in a tissue-specific manner. An abundance of NKA α, β, and FXYD1 subunits is well-described in human skeletal muscle, but not much is known about FXYD5 (dysadherin), a regulator of NKA and β1 subunit glycosylation, especially with regard to fibre-type specificity and influence of sex and exercise training. Here, we investigated muscle fibre-type specific adaptations in FXYD5 and glycosylated NKAβ1 to high-intensity interval training (HIIT), as well as sex differences in FXYD5 abundance. In nine young males (23.8 ± 2.5 years of age) (mean ± SD), 3 weekly sessions of HIIT for 6 weeks enhanced muscle endurance (220 ± 102 vs. 119 ± 99 s, p < 0.01) and lowered leg K+ release during intense knee-extensor exercise (0.5 ± 0.8 vs. 1.0 ± 0.8 mmol·min–1, p < 0.01) while also increasing cumulated leg K+ reuptake 0–3 min into recovery (2.1 ± 1.5 vs. 0.3 ± 0.9 mmol, p < 0.01). In type IIa muscle fibres, HIIT lowered FXYD5 abundance (p < 0.01) and increased the relative distribution of glycosylated NKAβ1 (p < 0.05). FXYD5 abundance in type IIa muscle fibres correlated inversely with the maximal oxygen consumption (r = –0.53, p < 0.05). NKAα2 and β1 subunit abundances did not change with HIIT. In muscle fibres from 30 trained males and females, we observed no sex (p = 0.87) or fibre type differences (p = 0.44) in FXYD5 abundance. Thus, HIIT downregulates FXYD5 and increases the distribution of glycosylated NKAβ1 in type IIa muscle fibres, which is likely independent of a change in the number of NKA complexes. These adaptations may contribute to counter exercise-related K+ shifts and enhance muscle performance during intense exercise.

The mitochondrial mRNA stabilizing protein, SLIRP, regulates skeletal muscle mitochondrial structure and respiration by exercise-recoverable mechanisms

“…5D) and LRPPRC (+50%, Fig. 6F) in healthy young men 65 . Thus, the exercise training response of SLIRP was highly consistent, independent of sex, and responsive to various exercise modalities.…”

“…(D-F) Immunoblotting of SLIRP (E) and LRPPRC (F) protein in vastus lateralis of healthy young men (n=6/group, ( ○ Pre ET, □ Post ET)) after a 6-week high intensity interval training 65 .…”

“…SLIRP and LRPPRC protein content were determined in human skeletal muscle in four independent exercise cohorts employing different exercise modalities in conjunction with or without aging or diabetes and in males and females. Participant characteristics and study designs for the different ET modalities have been published previously for all the clinical studies [62][63][64][65] .…”

“…Clinical experiments were approved by the Ethics Committee of Copenhagen or by the Regional Scientific Ethical Committees for Southern Denmark and performed in accordance with the Helsinki Declaration II. Studies including human study participants are described in Ref [62][63][64][65]…”

“…A detailed description of the study participants, research design and methods has been previously published 65 . In the present study, we included vastus lateralis muscle lysate for immunoblotting obtained from 6 healthy young men before and after 6-week HIIT training.…”