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Gazzetta Medica Italiana - Archivio per le Scienze Mediche 2020 October;179(10):581-93

DOI: 10.23736/S0393-3660.19.04238-4


language: English

Influence of physical activity on structure and function of the RyR1 calcium channel: a systematic review

Alberto ZULLO 1, 2, Giulia FRISSO 2, 3, Antonella CARSANA 3

1 Department of Sciences and Technologies, University of Sannio, Benevento, Italy; 2 CEINGE Advanced Biotechnologies, Naples, Italy; 3 Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, Naples, Italy

INTRODUCTION: Calcium release through ryanodine receptor type 1 (RyR1) channel triggers skeletal muscle contraction, which is finely regulated during physical activity allowing muscles to adapt to stress. However, both prolonged physical activity and inactivity decrease contractile function. The adaptive mechanisms are related to changes in structure, function, and expression of RyR1 channel.
EVIDENCE ACQUISITION: The search on the effects of physical activities on RyR1 structure and function covered PubMed and Scopus databases from 2008 onward. The search term used was RyR1 combined with exercise, fatigue, exertional rhabdomyolysis, or aging.
EVIDENCE SYNTHESIS: Physical activity induces RyR1 dynamic post-translational modifications, driven essentially by increased reactive oxygen and nitrogen species. RyR1 redox-dependent modifications increase channel activity, but impaired Ca2+ handling may lead to muscle fatigue. Furthermore, imbalance of redox equilibrium may induce RyR1 fragmentation. During exercise RyR1 is also hyperphosphorylated and dissociated from its stabilizing subunit calstabin1, resulting in “leaky” channels and decreased exercise tolerance. RyR1 modifications also occur during aging. Conversely, reduced RyR1 protein expression occurs in some pathophysiological conditions characterized by low-exercise capacity, i.e., heart failure and prolonged bed rest. Impaired muscle performance is also linked to RyR1 mutations, with altered channel structure and/or function. Moreover, in apparently healthy subjects with RyR1 mutations, physical exercise can trigger skeletal muscle stiffness at low temperatures, or exertional rhabdomyolysis.
CONCLUSIONS: We provide an overview of the molecular aspects linking skeletal muscle activity to RyR1 modifications, with particular attention to the effects produced by different type of exercises, i.e. aerobic and anaerobic exercise, by some pathophysiological conditions, by age-related loss of muscle function and by RyR1 mutations.

KEY WORDS: Exercise; Ryanodine receptor calcium release channel; Reactive oxygen species; Reactive nitrogen species; Gene expression

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