Molecular stressors underlying exercise training-induced improvements in K+ regulation during exercise and Na+,K+-ATPase adaptation in human skeletal muscle

Danny Christiansen

doi:10.1111/apha.13196

Molecular stressors underlying exercise training-induced improvements in K⁺ regulation during exercise and Na⁺,K⁺-ATPase adaptation in human skeletal muscle

Danny Christiansen^*

^*Corresponding author af dette arbejde

August Krogh Sektionen for Human Fysiologi

14 Citationer (Scopus)

Abstract

Despite substantial progress made towards a better understanding of the importance of skeletal muscle K⁺ regulation for human physical function and its association with several disease states (eg type-II diabetes and hypertension), the molecular basis underpinning adaptations in K⁺ regulation to various stimuli, including exercise training, remains inadequately explored in humans. In this review, the molecular mechanisms essential for enhancing skeletal muscle K⁺ regulation and its key determinants, including Na⁺,K⁺-ATPase function and expression, by exercise training are examined. Special attention is paid to the following molecular stressors and signaling proteins: oxygenation, redox balance, hypoxia, reactive oxygen species, antioxidant function, Na⁺,K⁺, and Ca²⁺ concentrations, anaerobic ATP turnover, AMPK, lactate, and mRNA expression. On this basis, an update on the effects of different types of exercise training on K⁺ regulation in humans is provided, focusing on recent discoveries about the muscle fibre-type-dependent regulation of Na⁺,K⁺-ATPase-isoform expression. Furthermore, with special emphasis on blood-flow-restricted exercise as an exemplary model to modulate the key molecular mechanisms identified, it is discussed how training interventions may be designed to maximize improvements in K⁺ regulation in humans. The novel insights gained from this review may help us to better understand how exercise training and other strategies, such as pharmacological interventions, may be best designed to enhance K⁺ regulation and thus the physical function in humans.

Originalsprog	Engelsk
Artikelnummer	e13196
Tidsskrift	Acta Physiologica (Print)
Vol/bind	225
Udgave nummer	3
Antal sider	35
ISSN	1748-1708
DOI	https://doi.org/10.1111/apha.13196
Status	Udgivet - mar. 2019

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10.1111/apha.13196

Citationsformater

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title = "Molecular stressors underlying exercise training-induced improvements in K+ regulation during exercise and Na+,K+-ATPase adaptation in human skeletal muscle",

abstract = "Despite substantial progress made towards a better understanding of the importance of skeletal muscle K+ regulation for human physical function and its association with several disease states (eg type-II diabetes and hypertension), the molecular basis underpinning adaptations in K+ regulation to various stimuli, including exercise training, remains inadequately explored in humans. In this review, the molecular mechanisms essential for enhancing skeletal muscle K+ regulation and its key determinants, including Na+,K+-ATPase function and expression, by exercise training are examined. Special attention is paid to the following molecular stressors and signaling proteins: oxygenation, redox balance, hypoxia, reactive oxygen species, antioxidant function, Na+,K+, and Ca2+ concentrations, anaerobic ATP turnover, AMPK, lactate, and mRNA expression. On this basis, an update on the effects of different types of exercise training on K+ regulation in humans is provided, focusing on recent discoveries about the muscle fibre-type-dependent regulation of Na+,K+-ATPase-isoform expression. Furthermore, with special emphasis on blood-flow-restricted exercise as an exemplary model to modulate the key molecular mechanisms identified, it is discussed how training interventions may be designed to maximize improvements in K+ regulation in humans. The novel insights gained from this review may help us to better understand how exercise training and other strategies, such as pharmacological interventions, may be best designed to enhance K+ regulation and thus the physical function in humans.",

keywords = "Human skeletal muscle, Ion transport, Molecular mechanisms, Na+-K+-ATPase, Reactive oxygen species, Training adaptation",

author = "Danny Christiansen",

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N2 - Despite substantial progress made towards a better understanding of the importance of skeletal muscle K+ regulation for human physical function and its association with several disease states (eg type-II diabetes and hypertension), the molecular basis underpinning adaptations in K+ regulation to various stimuli, including exercise training, remains inadequately explored in humans. In this review, the molecular mechanisms essential for enhancing skeletal muscle K+ regulation and its key determinants, including Na+,K+-ATPase function and expression, by exercise training are examined. Special attention is paid to the following molecular stressors and signaling proteins: oxygenation, redox balance, hypoxia, reactive oxygen species, antioxidant function, Na+,K+, and Ca2+ concentrations, anaerobic ATP turnover, AMPK, lactate, and mRNA expression. On this basis, an update on the effects of different types of exercise training on K+ regulation in humans is provided, focusing on recent discoveries about the muscle fibre-type-dependent regulation of Na+,K+-ATPase-isoform expression. Furthermore, with special emphasis on blood-flow-restricted exercise as an exemplary model to modulate the key molecular mechanisms identified, it is discussed how training interventions may be designed to maximize improvements in K+ regulation in humans. The novel insights gained from this review may help us to better understand how exercise training and other strategies, such as pharmacological interventions, may be best designed to enhance K+ regulation and thus the physical function in humans.

AB - Despite substantial progress made towards a better understanding of the importance of skeletal muscle K+ regulation for human physical function and its association with several disease states (eg type-II diabetes and hypertension), the molecular basis underpinning adaptations in K+ regulation to various stimuli, including exercise training, remains inadequately explored in humans. In this review, the molecular mechanisms essential for enhancing skeletal muscle K+ regulation and its key determinants, including Na+,K+-ATPase function and expression, by exercise training are examined. Special attention is paid to the following molecular stressors and signaling proteins: oxygenation, redox balance, hypoxia, reactive oxygen species, antioxidant function, Na+,K+, and Ca2+ concentrations, anaerobic ATP turnover, AMPK, lactate, and mRNA expression. On this basis, an update on the effects of different types of exercise training on K+ regulation in humans is provided, focusing on recent discoveries about the muscle fibre-type-dependent regulation of Na+,K+-ATPase-isoform expression. Furthermore, with special emphasis on blood-flow-restricted exercise as an exemplary model to modulate the key molecular mechanisms identified, it is discussed how training interventions may be designed to maximize improvements in K+ regulation in humans. The novel insights gained from this review may help us to better understand how exercise training and other strategies, such as pharmacological interventions, may be best designed to enhance K+ regulation and thus the physical function in humans.

KW - Human skeletal muscle

KW - Ion transport

KW - Molecular mechanisms

KW - Na+-K+-ATPase

KW - Reactive oxygen species

KW - Training adaptation

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