The Oxygen Conforming Response in Active Mouse Skeletal Muscle In Vitro: A Pilot Study

Human studies of the OCR have shown that reductions in oxygen availability quickly decrease force production, while subsequent reoxygenation produces a rapid recovery of force to pre-conformed levels. This readily reversible response remains poorly understood but appears to occur with minimal metabolic disturbance, suggesting a mechanism distinct from classical fatigue, which develops from the accumulation of ADP, Pi and H+. Although the OCR is theoretically distinct from fatigue, the well-documented fiber-specificity (fast > slow) of force modulation during fatigue suggests that inherent differences between muscle types may also influence force regulation during acute changes in oxygen availability. Therefore, we hypothesized that, in an in vitro mouse model, the OCR would display fiber type differences, with slow-twitch muscle being more sensitive to reductions in oxygen availability due to its greater reliance on oxidative phosphorylation. To test this, mouse soleus, SOL, (slow-twitch) and extensor digitorum longus, EDL, (fast-twitch) muscles were isolated and mounted in normally oxygenated Tyrode’s solution (22°C). Doublets delivered at regular intervals (0.4Hz) were provided to both muscle types. During stimulation, bath oxygen concentration was reduced from 32ppm to 20ppm and subsequently restored to 32ppm. Our results showed that during reduced oxygen availability, EDL force declined by 39% ± 0.07 (n = 10, p < 0.001) from baseline values. Upon reoxygenation, force returned to 82% ± 0.06 (p < 0.001) of baseline values. For SOL, when oxygen decreased, force declined by 17% ± 0.12 (n = 9, p < 0.001) from baseline values. Upon reoxygenation, force returned to 104% ± 0.06 (p < 0.001) of baseline values. The relative difference in force decline and recovery between EDL and SOL muscles was statistically different, with EDL exhibiting a greater decline in force by 22% ± 0.04 (p < 0.001). Conversely, SOL exhibited a greater force recovery by 22% ± 0.03 (p < 0.001). These data demonstrate that the OCR displays fiber type differences in mouse muscle in vitro, with fast-twitch muscle being more sensitive to oxygen changes than slow-twitch muscle. The mechanism of the OCR remains unknown and requires further investigation to understand how intracellular oxygen is sensed and regulated.

Name thesis:degree_name

M.Sc. Applied Health Sciences

Level thesis:degree_level

Master

Discipline thesis:degree_discipline

Faculty of Applied Health Sciences

Department dc:contributor.department

Applied Health Sciences Program

Grantor dc:publisher

Brock University

Year dc:date.issued

2025

Author dc:creator

• Hambly, Addie

Advisor dc:contributor.advisor

• Vandenboom, Rene

• MEDICINE::Morphology, cell biology, pathology::Morphology::Anatomy
• MEDICINE::Physiology and pharmacology
• MEDICINE::Physiology and pharmacology::Physiology::Laboratory animal science

Statement dc:rights

• Attribution-NonCommercial-NoDerivatives 4.0 International

Licence dc:rights.uri

• http://creativecommons.org/licenses/by-nc-nd/4.0/

Language dc:language.iso

eng

Handle dc:identifier.uri

https://hdl.handle.net/10464/19970

OAI identifier oai:identifier

oai:brocku.scholaris.ca:10464/19970