Increased fatigue resistance linked to Ca(2+)-stimulated mitochondrial biogenesis in muscle fibres of cold-acclimated mice
2010 (English)In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 588, no 21, 4275-4288 p.Article in journal (Refereed) Published
Mammals exposed to a cold environment initially generate heat by repetitive muscle activity (shivering). Shivering is successively replaced by the recruitment of uncoupling protein-1 (UCP1)-dependent heat production in brown adipose tissue. Interestingly, adaptations observed in skeletal muscles of cold-exposed animals are similar to those observed with endurance training. We hypothesized that increased myoplasmic free [Ca2+] ([Ca2+]i) is important for these adaptations. To test this hypothesis, experiments were performed on flexor digitorum brevis (FDB) muscles, which do not participate in the shivering response, of adult wild-type (WT) and UCP1-ablated (UCP1-KO) mice kept either at room temperature (24 ºC) or cold-acclimated (4 ºC) for 4-5 weeks. [Ca2+]i (measured with indo-1) and force were measured under control conditions and during fatigue induced by repeated tetanic stimulation in intact single fibres. The results show no differences between fibres from WT and UCP1-KO mice. However, muscle fibres from cold-acclimated mice showed significant increases in basal [Ca2+]i (~50%), tetanic [Ca2+]i (~40%), and sarcoplasmic reticulum (SR) Ca2+ leak (~four-fold) as compared to fibres from room-temperature mice. Muscles of cold-acclimated mice showed increased expression of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) and increased citrate synthase activity (reflecting increased mitochondrial content). Fibres of cold-acclimated mice were more fatigue resistant with higher tetanic [Ca2+]i and less force loss during fatiguing stimulation. In conclusion, cold exposure induces changes in FDB muscles similar to those observed with endurance training and we propose that increased [Ca2+]i is a key factor underlying these adaptations.
Place, publisher, year, edition, pages
2010. Vol. 588, no 21, 4275-4288 p.
IdentifiersURN: urn:nbn:se:su:diva-45468DOI: 10.1113/jphysiol.2010.198598ISI: 000283718800024PubMedID: 20837639OAI: oai:DiVA.org:su-45468DiVA: diva2:369185