Evidence map›Paper›PMID 26575622›Full record

Trial reportProceedings of the National Academy of Sciences of the United States of America2015

Ryanodine receptor fragmentation and sarcoplasmic reticulum Ca2+ leak after one session of high-intensity interval exercise.

Nicolas Place, Niklas Ivarsson, Tomas Venckunas, Daria Neyroud, Marius Brazaitis, Arthur J Cheng, Julien Ochala, Sigitas Kamandulis, Sebastien Girard, Gintautas Volungevičius and 10 more

Registry-linked trialOpen access · bronzeAbstract readClinical Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05350566 (Combined Effect of Exercise Intensity With Nutritional Supplementation on Skeletal Muscle Function), which is not on this map. Cited by 108 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
108citing papers in PubMed, 1 pooled it
27.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT05350566 nacompletednot on this mapstarted 2022, after this paper: background citation

Combined Effect of Exercise Intensity With Nutritional Supplementation on Skeletal Muscle Function

TypeinterventionalSponsorUniversity of LausanneRan2022 to 2022Enrolled25ConditionsHealthy Volunteers, Exercise Intensity, Neuromuscular Fatigue, Skeletal Muscle AdaptationsArmsOlive leaf extract, Placebo
3 · Its place in the literature

Who cites it

108 citing papers in PubMed, 1 synthesis or guideline pooled it, 177 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Exercise capacity in RYR1-related myopathies.Orphanet journal of rare diseases · 2025
    Trial
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  18. Proteoforms as the true units of physiological function.European journal of applied physiology · 2026
    Review
  19. Article
  20. Physical Activity and Its Impact on Cardiometabolic Disorders.Handbook of experimental pharmacology · 2026
    Review

48 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 7 institutions in 5 countries.

Nicolas PlaceInstitute of Sport Sciences and Department of Physiology, Faculty of Biology and Medicine, University of Lausanne, 1015 Lausanne, Switzerland;
Niklas IvarssonDepartment of Physiology and Pharmacology, Karolinska Institutet, SE 171 77 Stockholm, Sweden;
Tomas VenckunasSports Science and Innovation Institute, Lithuanian Sports University, LT-44221 Kaunas, Lithuania;
Daria NeyroudInstitute 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;
Marius BrazaitisSports Science and Innovation Institute, Lithuanian Sports University, LT-44221 Kaunas, Lithuania;
Arthur J ChengDepartment of Physiology and Pharmacology, Karolinska Institutet, SE 171 77 Stockholm, Sweden;
Julien OchalaCentre of Human and Aerospace Physiological Sciences, King's College London, London SE1 1UL, United Kingdom;
Sigitas KamandulisSports Science and Innovation Institute, Lithuanian Sports University, LT-44221 Kaunas, Lithuania;
Sebastien GirardInstitute of Movement Sciences and Sports Medicine, University of Geneva, 1205 Geneva, Switzerland;
Gintautas VolungevičiusSports Science and Innovation Institute, Lithuanian Sports University, LT-44221 Kaunas, Lithuania;
Henrikas PaužasSurgery Department, Lithuanian University of Health Sciences, LT-50009 Kaunas, Lithuania;
Abdelhafid MekidecheElectroneuromyography and Neuromuscular Disorders Unit, Department of Clinical Neurosciences, Geneva University Hospital, 1211 Geneva, Switzerland.
Bengt KayserInstitute of Sport Sciences and Department of Physiology, Faculty of Biology and Medicine, University of Lausanne, 1015 Lausanne, Switzerland;
Vicente Martinez-RedondoDepartment of Physiology and Pharmacology, Karolinska Institutet, SE 171 77 Stockholm, Sweden;
Jorge L RuasDepartment of Physiology and Pharmacology, Karolinska Institutet, SE 171 77 Stockholm, Sweden;ORCID http://orcid.org/0000-0002-1110-2606
Joseph BrutonDepartment of Physiology and Pharmacology, Karolinska Institutet, SE 171 77 Stockholm, Sweden;
Andre TruffertElectroneuromyography and Neuromuscular Disorders Unit, Department of Clinical Neurosciences, Geneva University Hospital, 1211 Geneva, Switzerland.
Johanna T LannerDepartment of Physiology and Pharmacology, Karolinska Institutet, SE 171 77 Stockholm, Sweden;
Albertas SkurvydasSports Science and Innovation Institute, Lithuanian Sports University, LT-44221 Kaunas, Lithuania;
Håkan WesterbladDepartment 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.
Karolinska Institutet · SELithuanian Sports University · LTUniversity Hospital of Geneva · CHUniversity of Geneva · CHUniversity of Lausanne · CHKing's College London · GBLithuanian University of Health Sciences · LT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

AdultAnimalsAthletesCalciumExerciseHumansMaleMiceMice, Inbred C57BLMuscle Fibers, SkeletalPhysical EnduranceReactive Oxygen SpeciesRecreationRyanodine Receptor Calcium Release ChannelSarcoplasmic ReticulumCalciumReactive Oxygen SpeciesRyanodine Receptor Calcium Release ChannelCa2+high-intensity exercisereactive oxygen speciesryanodine receptor 1skeletal muscle

Identifiers

PMID26575622
PMCPMC4687604
OpenAlexW1942141121

What OpenQuestion holds

Textmetadata
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.