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The molecular basis of acid insensitivity in the African naked mole-rat

Official URL:https://doi.org/10.1126/science.1213760
PubMed:View item in PubMed
Creators Name:Smith, E.S. and Omerbasic, D. and Lechner, S.G. and Anirudhan, G. and Lapatsina, L. and Lewin, G.R.
Journal Title:Science
Journal Abbreviation:Science
Volume:334
Number:6062
Page Range:1557-1560
Date:16 December 2011
Keywords:Naked Mole Rat, Animals, Mice, Rats
Abstract: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.
ISSN:0036-8075
Publisher:American Association for the Advancement of Science (U.S.A.)
Item Type:Article

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