title: Ryanodine receptor fragmentation and sarcoplasmic reticulum Ca2+ leak after one session of high-intensity interval exercise.
abstract: High-intensity interval training (HIIT) is a time-efficient way of improving physical performance in healthy subjects and in patients with common chronic diseases, but less so in elite endurance athletes. The mechanisms underlying the effectiveness of HIIT are uncertain. Here, recreationally active human subjects performed highly demanding HIIT consisting of 30-s bouts of all-out cycling with 4-min rest in between bouts (≤3 min total exercise time). Skeletal muscle biopsies taken 24 h after the HIIT exercise showed an extensive fragmentation of the sarcoplasmic reticulum (SR) Ca(2+) release channel, the ryanodine receptor type 1 (RyR1). The HIIT exercise also caused a prolonged force depression and triggered major changes in the expression of genes related to endurance exercise. Subsequent experiments on elite endurance athletes performing the same HIIT exercise showed no RyR1 fragmentation or prolonged changes in the expression of endurance-related genes. Finally, mechanistic experiments performed on isolated mouse muscles exposed to HIIT-mimicking stimulation showed reactive oxygen/nitrogen species (ROS)-dependent RyR1 fragmentation, calpain activation, increased SR Ca(2+) leak at rest, and depressed force production due to impaired SR Ca(2+) release upon stimulation. In conclusion, HIIT exercise induces a ROS-dependent RyR1 fragmentation in muscles of recreationally active subjects, and the resulting changes in muscle fiber Ca(2+)-handling trigger muscular adaptations. However, the same HIIT exercise does not cause RyR1 fragmentation in muscles of elite endurance athletes, which may explain why HIIT is less effective in this group.
authors.affiliation: Institute of Sport Sciences and Department of Physiology, Faculty of Biology and Medicine, University of Lausanne, 1015 Lausanne, Switzerland;
authors.forename: Nicolas
authors.initials: N
authors.lastname: Place
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, SE 171 77 Stockholm, Sweden;
authors.forename: Niklas
authors.initials: N
authors.lastname: Ivarsson
authors.affiliation: Sports Science and Innovation Institute, Lithuanian Sports University, LT-44221 Kaunas, Lithuania;
authors.forename: Tomas
authors.initials: T
authors.lastname: Venckunas
authors.affiliation: Institute of Sport Sciences and Department of Physiology, Faculty of Biology and Medicine, University of Lausanne, 1015 Lausanne, Switzerland; Institute of Movement Sciences and Sports Medicine, University of Geneva, 1205 Geneva, Switzerland;
authors.forename: Daria
authors.initials: D
authors.lastname: Neyroud
authors.affiliation: Sports Science and Innovation Institute, Lithuanian Sports University, LT-44221 Kaunas, Lithuania;
authors.forename: Marius
authors.initials: M
authors.lastname: Brazaitis
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, SE 171 77 Stockholm, Sweden;
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Cheng
authors.affiliation: Centre of Human and Aerospace Physiological Sciences, King's College London, London SE1 1UL, United Kingdom;
authors.forename: Julien
authors.initials: J
authors.lastname: Ochala
authors.affiliation: Sports Science and Innovation Institute, Lithuanian Sports University, LT-44221 Kaunas, Lithuania;
authors.forename: Sigitas
authors.initials: S
authors.lastname: Kamandulis
authors.affiliation: Institute of Movement Sciences and Sports Medicine, University of Geneva, 1205 Geneva, Switzerland;
authors.forename: Sebastien
authors.initials: S
authors.lastname: Girard
authors.affiliation: Sports Science and Innovation Institute, Lithuanian Sports University, LT-44221 Kaunas, Lithuania;
authors.forename: Gintautas
authors.initials: G
authors.lastname: Volungevičius
authors.affiliation: Surgery Department, Lithuanian University of Health Sciences, LT-50009 Kaunas, Lithuania;
authors.forename: Henrikas
authors.initials: H
authors.lastname: Paužas
authors.affiliation: Electroneuromyography and Neuromuscular Disorders Unit, Department of Clinical Neurosciences, Geneva University Hospital, 1211 Geneva, Switzerland.
authors.forename: Abdelhafid
authors.initials: A
authors.lastname: Mekideche
authors.affiliation: Institute of Sport Sciences and Department of Physiology, Faculty of Biology and Medicine, University of Lausanne, 1015 Lausanne, Switzerland;
authors.forename: Bengt
authors.initials: B
authors.lastname: Kayser
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, SE 171 77 Stockholm, Sweden;
authors.forename: Vicente
authors.initials: V
authors.lastname: Martinez-Redondo
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, SE 171 77 Stockholm, Sweden;
authors.forename: Jorge L
authors.identifier: http://orcid.org/0000-0002-1110-2606
authors.initials: JL
authors.lastname: Ruas
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, SE 171 77 Stockholm, Sweden;
authors.forename: Joseph
authors.initials: J
authors.lastname: Bruton
authors.affiliation: Electroneuromyography and Neuromuscular Disorders Unit, Department of Clinical Neurosciences, Geneva University Hospital, 1211 Geneva, Switzerland.
authors.forename: Andre
authors.initials: A
authors.lastname: Truffert
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, SE 171 77 Stockholm, Sweden;
authors.forename: Johanna T
authors.initials: JT
authors.lastname: Lanner
authors.affiliation: Sports Science and Innovation Institute, Lithuanian Sports University, LT-44221 Kaunas, Lithuania;
authors.forename: Albertas
authors.initials: A
authors.lastname: Skurvydas
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, SE 171 77 Stockholm, Sweden; Sports Science and Innovation Institute, Lithuanian Sports University, LT-44221 Kaunas, Lithuania; hakan.westerblad@ki.se.
authors.forename: Håkan
authors.initials: H
authors.lastname: Westerblad
mesh_terms: D000328:Adult; D000818:Animals; D056352:Athletes; D002118:Calcium / Q000378:metabolism*; D015444:Exercise / Q000502:physiology*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018485:Muscle Fibers, Skeletal / Q000502:physiology; D010807:Physical Endurance; D017382:Reactive Oxygen Species / Q000378:metabolism; D011998:Recreation; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium
keywords: Ca2+; high-intensity exercise; reactive oxygen species; ryanodine receptor 1; skeletal muscle