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Nonshivering thermogenesis protects against defective calcium handling in muscle
Author(s) -
Aydin Jan,
Shabalina Irina G.,
Place Nicolas,
Reiken Steven,
Zhang ShiJin,
Bellinger Andrew M.,
Nedergaard Jan,
Can Barbara,
Marks Andrew R.,
Bruton Joseph D.,
Westerblad Håkan
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.08-113712
Subject(s) - thermogenin , shivering , brown adipose tissue , medicine , endocrinology , thermogenesis , skeletal muscle , ryanodine receptor , chemistry , soleus muscle , calcium , adipose tissue , biology , physiology
When acutely exposed to a cold environment, mammals shiver to generate heat. During prolonged cold exposure, shivering is replaced by adaptive adrenergic nonshivering thermogenesis with increased heat production in brown adipose tissue due to activation of uncoupling protein‐1 (UGP1). This cold acclimation is associated with chronically increased sympathetic stimulation of skeletal muscle, which may increase the sarcoplasmic reticulum (SR) Ca 2+ leak via destabilized ryanodine receptor 1 (RyR1) channel complexes. Here, we use genetically engineered UGP1‐deficient (UGP1‐KO) mice that rely completely on shivering in the cold. We examine soleus muscle, which participates in shivering, and flexor digitorum brevis (FDB) muscle, a distal and superficial muscle that does not shiver. Soleus muscles of cold‐acclimated UGP1‐KO mice exhibited severe RyR1 PKA hyperphosphorylation and calstabin1 depletion, as well as markedly decreased SR Ca 2+ release and force during contractions. In stark contrast, the RyR1 channel complexes were little affected, and Ca 2+ and force were not decreased in FDB muscles of cold‐acclimated UGP1‐KO mice. These results indicate that activation of UGP1‐mediated heat production in brown adipose tissue during cold exposure reduces the necessity for shivering and thus prevents the development of severe dysfunction in shivering muscles.— Aydin, J., Shabalina, I. G., Place, N., Reiken, S., Zhang, S.‐J., Bellinger, A. M., Nedergaard, J., Cannon, B., Marks, A. R., Bruton, J. D., Westerblad, H. Nonshivering thermogenesis protects against defective calcium handling in muscle. FASEB J. 22, 3919–3924 (2008)