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Publication : Increased fatigue resistance linked to Ca2+-stimulated mitochondrial biogenesis in muscle fibres of cold-acclimated mice.

First Author  Bruton JD Year  2010
Journal  J Physiol Volume  588
Issue  Pt 21 Pages  4275-88
PubMed ID  20837639 Mgi Jnum  J:179545
Mgi Id  MGI:5302627 Doi  10.1113/jphysiol.2010.198598
Citation  Bruton JD, et al. (2010) Increased fatigue resistance linked to Ca2+-stimulated mitochondrial biogenesis in muscle fibres of cold-acclimated mice. J Physiol 588(Pt 21):4275-88
abstractText  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 degrees C) or cold-acclimated (4 degrees C) 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 ( approximately 50%), tetanic [Ca2+]i ( approximately 40%), and sarcoplasmic reticulum (SR) Ca2+ leak ( approximately fourfold) as compared to fibres from room-temperature mice. Muscles of cold-acclimated mice showed increased expression of peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) 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.
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