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Science 334 (6062): 1557-1560

Copyright © 2011 by the American Association for the Advancement of Science

The Molecular Basis of Acid Insensitivity in the African Naked Mole-Rat

Ewan St. John Smith,* Damir Omerbasic, Stefan G. Lechner, Gireesh Anirudhan, Liudmila Lapatsina, Gary R. Lewin*

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 NaV1.7, which is potently blocked by protons and can account for acid insensitivity in this species. Thus, evolutionary pressure has selected for an NaV1.7 gene variant that tips the balance from proton-induced excitation to inhibition of action potential initiation to abolish acid nociception.

Department of Neuroscience, Max-Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin-Buch, Germany.

* To whom correspondence should be addressed. E-mail: glewin{at}mdc-berlin.de (G.R.L.); ewan.smith{at}mdc-berlin.de (E.St.J.S.)


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