Increased fatigue resistance linked to Ca2+-stimulated mitochondrial biogenesis in muscle fibres of cold-acclimated mice.
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°C) or cold-acclimated (4°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 (∼50%), tetanic [Ca2+]i (∼40%), and sarcoplasmic reticulum (SR) Ca2+ leak (∼fourfold) 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.
Bruton
Joseph D
JD
Department of Physiology and Pharmacology, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Aydin
Jan
J
Yamada
Takashi
T
Shabalina
Irina G
IG
Ivarsson
Niklas
N
Zhang
Shi-Jin
SJ
Wada
Masanobu
M
Tavi
Pasi
P
Nedergaard
Jan
J
Katz
Abram
A
Westerblad
Håkan
H
D000222:Adaptation, Physiological / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000502:physiology*; D003080:Cold Temperature; D005260:Female; D007473:Ion Channels / Q000235:genetics / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008931:Mitochondria, Muscle / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000502:physiology; D023421:Models, Animal; D018763:Muscle Fatigue / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000502:physiology*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012768:Shivering / Q000502:physiology; D015534:Trans-Activators / Q000502:physiology; D014157:Transcription Factors; D000071256:Uncoupling Protein 1
D007473:Ion Channels; D024101:Mitochondrial Proteins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D002118:Calcium