Nonshivering thermogenesis protects against defective calcium handling in muscle.

Details

Serval ID
serval:BIB_4A1F310DF2B9
Type
Article: article from journal or magazin.
Collection
Publications
Title
Nonshivering thermogenesis protects against defective calcium handling in muscle.
Journal
FASEB Journal
Author(s)
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.
ISSN
1530-6860 (Electronic)
ISSN-L
0892-6638
Publication state
Published
Issued date
2008
Volume
22
Number
11
Pages
3919-3924
Language
english
Abstract
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 (UCP1). 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 UCP1-deficient (UCP1-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 UCP1-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 UCP1-KO mice. These results indicate that activation of UCP1-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.
Keywords
Acclimatization/physiology, Adipose Tissue, Brown/metabolism, Animals, Calcium/metabolism, Cold Temperature, Cyclic AMP-Dependent Protein Kinases/genetics, Cyclic AMP-Dependent Protein Kinases/metabolism, Ion Channels/genetics, Ion Channels/metabolism, Mice, Mice, Knockout, Mitochondrial Proteins/genetics, Mitochondrial Proteins/metabolism, Muscle Proteins/genetics, Muscle Proteins/metabolism, Muscle, Skeletal/metabolism, Phosphorylation, Ryanodine Receptor Calcium Release Channel/genetics, Ryanodine Receptor Calcium Release Channel/metabolism, Shivering/physiology, Thermogenesis/physiology
Pubmed
Web of science
Create date
20/09/2013 8:40
Last modification date
20/08/2019 13:57
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