Proceedings of The Physiological Society
University of Manchester (2010) Proc Physiol Soc 19, C15
Increased calcium stimulates mitochondrial biogenesis in fast twitch muscle fibres in vivo
H. Westerblad1, N. Ivarsson1, T. Yamada1, J. D. Bruton1
1. Department of Physiology & Pharmacology, Karolinska Institutet, Stockholm, Sweden.
The physiological triggers for the beneficial effects of endurance training are still uncertain. In the present study we hypothesized that increased myoplasmic free [Ca2+] ([Ca2+]i) can be a major signalling event underlying the increased mitochondrial biogenesis, and hence increased fatigue resistance, observed in skeletal muscle with endurance training. To test this hypothesis, we used mice exposed to a cold environment as a model because skeletal muscles of cold exposed mammals show: (i) adaptations similar to those obtained with endurance training; (ii) changes in the ryanodine receptor complex which indicate altered Ca2+ handling. Experiments were performed on flexor digitorum brevis (FDB) muscles of mice either kept at room temperature (24°C) or cold-acclimated (4°C) for 4-5 weeks. Myoplasmic free [Ca2+] ([Ca2+]i; measured with indo-1) and force were measured under resting conditions and during fatigue induced by repeated tetanic stimulation in intact single fibres. Data are presented as mean ± SEM. Compared to muscle fibres from mice kept at room temperature, fibres from cold-acclimated mice showed increases in basal [Ca2+]i (86 ± 8 nM (n = 10) vs. 57 ± 7 nM (n = 12); P < 0.01), tetanic [Ca2+]i (3.09 ± 0.34 µM vs. 2.03 ± 0.30 µM; P < 0.01), and SR Ca2+ leak (~four-fold). Muscle fibres of cold-acclimated mice were more fatigue resistant than fibres of room temperature mice. Moreover, muscles of cold-acclimated mice showed increases in citrate synthase activity (reflecting increased mitochondrial content) and the expression of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α; a key regulator of mitochondrial biogenesis). In conclusion, the present results support the notion that increased [Ca2+]i has an important role in the increases of oxidative capacity and endurance observed in skeletal muscle with cold exposure as well as with endurance training.
Where applicable, experiments conform with Society ethical requirements