Document Detail

The molecular basis of acid insensitivity in the African naked mole-rat.
MedLine Citation:
PMID:  22174253     Owner:  NLM     Status:  In-Process    
Acid evokes pain by exciting nociceptors; the acid sensors are proton-gated ion channels that depolarize neurons. The naked mole-rat (Heterocephalus glaber) is exceptional in its acid insensitivity, but acid sensors (acid-sensing ion channels and the transient receptor potential vanilloid-1 ion channel) in naked mole-rat nociceptors are similar to those in other vertebrates. Acid inhibition of voltage-gated sodium currents is more profound in naked mole-rat nociceptors than in mouse nociceptors, however, which effectively prevents acid-induced action potential initiation. We describe a species-specific variant of the nociceptor sodium channel Na(V)1.7, which is potently blocked by protons and can account for acid insensitivity in this species. Thus, evolutionary pressure has selected for an Na(V)1.7 gene variant that tips the balance from proton-induced excitation to inhibition of action potential initiation to abolish acid nociception.
Ewan St John Smith; Damir Omerbašić; Stefan G Lechner; Gireesh Anirudhan; Liudmila Lapatsina; Gary R Lewin
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Science (New York, N.Y.)     Volume:  334     ISSN:  1095-9203     ISO Abbreviation:  Science     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0404511     Medline TA:  Science     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1557-60     Citation Subset:  IM    
Department of Neuroscience, Max-Delbrück Center for Molecular Medicine, Berlin-Buch, Germany.
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