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Increased fatigue resistance linked to Ca 2+ ‐stimulated mitochondrial biogenesis in muscle fibres of cold‐acclimated mice
Author(s) -
Bruton Joseph D.,
Aydin Jan,
Yamada Takashi,
Shabalina Irina G.,
Ivarsson Niklas,
Zhang ShiJin,
Wada Masanobu,
Tavi Pasi,
Nedergaard Jan,
Katz Abram,
Westerblad Håkan
Publication year - 2010
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2010.198598
Subject(s) - medicine , thermogenesis , endocrinology , stimulation , mitochondrial biogenesis , shivering , skeletal muscle , thermogenin , chemistry , endoplasmic reticulum , brown adipose tissue , citrate synthase , mitochondrion , biology , adipose tissue , biochemistry , physiology , enzyme
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 [Ca 2+ ] ([Ca 2+ ] 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. [Ca 2+ ] 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 [Ca 2+ ] i (∼50%), tetanic [Ca 2+ ] i (∼40%), and sarcoplasmic reticulum (SR) Ca 2+ 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 [Ca 2+ ] 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 [Ca 2+ ] i is a key factor underlying these adaptations.