Skeletal Muscle Fibers of Cold-Acclimated Mice Display Increases in Basal Calcium, Mitochondrial Content and Fatigue Resistance

Abstract

Mammals initially generate heat by repetitive muscle activity (shivering) when exposed to a cold environment. Shivering can later be replaced by heat generated in brown adipose tissue by activation of uncoupling protein-1 (UCP1). Interestingly, adaptations in skeletal muscles of cold exposed animals are similar to those obtained with endurance training. We studied the function of non-shivering flexor digitorum brevis (FDB) muscles of wild-type (WT) and UCP1-KO mice 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 fibers. We observed no differences between fibers from WT and UCP1-KO mice. On the other hand, muscle fibers from cold-acclimated mice showed increases in basal [Ca2+]i (∼50%), tetanic [Ca2+]i (∼40%), and SR Ca2+ leak (∼four-fold) as compared to fibers from room-temperature mice. Muscles of cold-acclimated mice also showed increases in expression of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), citrate synthase activity (reflecting increased mitochondrial content), and fatigue resistance. In conclusion, cold exposure induces changes in FDB muscles similar to those observed with endurance training and we propose that increased basal [Ca2+]i has a key role in these adaptations.