Fatiguing high-intensity intermittent exercise depresses maximal Na+-K+-ATPase activity in human skeletal muscle assessed using a novel NADH-coupled assay
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The Na + -K + -ATPase is a critical regulator of ion homeostasis during contraction, buffering interstitial K + accumulation, which is linked to muscle fatigue during intense exercise. Within this context, we adopted a recently reported methodology to examine exercise-induced alterations in maximal Na + -K + -ATPase activity. Eighteen trained healthy young males completed a repeated high-intensity cycling protocol consisting of three periods (EX1-EX3) of intermittent exercise. Each period comprised 10 × 45-s cycling at ~ 105% W max and a repeated sprint test. Muscle biopsies were sampled at baseline and after EX3 for determination of maximal in vitro Na + -K + -ATPase activity. Blood was drawn after each period and in association with a 2-min cycling test at a standardized high intensity (~ 90% W max ) performed before and after the session to assess plasma K + accumulation. Further, a 5-h recovery period with the ingestion of carbohydrate or placebo supplementation was implemented to explore potential effects of carbohydrate availability before sampling a final biopsy and repeating all tests. A ~ 12% reduction in maximal Na + -K + -ATPase activity was demonstrated following EX3 compared to baseline (25.2 ± 3.9 vs. 22.4 ± 4.8 μmol·min −1 ·g −1 protein, P = 0.039), which was sustained at the recovery time point (~ 15% decrease compared to baseline to 21.6 ± 5.9 μmol·min −1 ·g −1 protein, P = 0.008). No significant effect of carbohydrate supplementation was observed on maximal Na + -K + -ATPase activity after recovery ( P = 0.078). In conclusion, we demonstrate an exercise-induced depression of maximal Na + -K + -ATPase activity following high-intensity intermittent exercise, which was sustained during a 5-h recovery period and unrelated to carbohydrate availability under the present experimental conditions. This was shown using a novel NADH coupled assay and confirms previous findings using other methodological approaches.
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High-intensity intermittent exercise induces a sustained reduction in Na+/K+-ATPase activity in skeletal muscle that persists even after carbohydrate repletion, suggesting impaired potassium handling after exercise.
“Supporting this, Vigh-Larsen et al. [45] demonstrated that high-intensity intermittent exercise induces a sustained reduction in Na+/K+-ATPase activity in skeletal muscle; this decrease persists even after carbohydrate repletion, suggesting impaired potassium handling after exercise.”
From Thyrotoxic Hypokalemic Periodic Paralysis: Pathophysiological Mechanisms (2025) · cites this paper as [45]
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Thyrotoxic Hypokalemic Periodic Paralysis: Pathophysiological Mechanisms
Qing, G., Zakaria, W. N. A., Rom, F. Z. M., Nik, W. N. F. H. W., Zulkeflee, H. A., & Rahim, S. N. A. (2025) · Endocrinology and Metabolism · doi:10.3803/enm.2025.2554 · Cited by 5 · see citing works
“Supporting this, Vigh-Larsen et al. [45] demonstrated that high-intensity intermittent exercise induces a sustained reduction in Na + /K + ATPase activity in skeletal muscle; this decrease persists even after carbohydrate repletion, suggesting impaired potassium handling after exercise.”
- Authors
- Vigh-Larsen, J. F., Frangos, S. M., Overgaard, K., Holloway, G. P., & Mohr, M.
- Affiliations
- University of Southern Denmark (DK)
- University of Guelph (CA)
- Aarhus University (DK)
- University of the Faroe Islands (FO)
- Corresponding author
- Vigh-Larsen, Jeppe F.
- Mohr, Magni
- Venue
- Pflügers Archiv - European Journal of Physiology
- Published
- 2024-11-14
- Volume
- 477
- Issue
- 2
- Pages
- 303-316
- ISSN
- 0031-6768 (ISSN-L)
- 1432-2013
- PMC
- PMC11761784
- OpenAlex
- W4404364739
- Cited by
- 6
- References
- 73
- Citations by year
- 2026: 2 · 2025: 4
- FWCI
- 3.00
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Pflügers Archiv - European Journal of Physiology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (submittedVersion, cc-by)
- Funders
- Kulturministeriet (FPK.2021-0055)
- The Faroese Research Council
- the A. P. Møller Foundation for the Advancement of Medical Science
- the Novo Nordisk Foundation Grant to Team Danmark (NNF 22SA0078293)
- NSERC Doctoral Scholarship
- Natural Sciences and Engineering Research Council of Canada (400362)
- University of Southern Denmark
- Topics
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Sports Performance and Training
- Keywords
- Na+/K+-ATPase, skeletal muscle fatigue, high-intensity intermittent exercise, repeated sprint test, carbohydrate supplementation, convalescence, ion homeostasis
- MeSH terms
- Sodium-Potassium-Exchanging ATPase, Adult, Humans, Male, NAD, Potassium, Exercise, Muscle, Skeletal, Muscle Fatigue, Young Adult
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