Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Logo for

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.)

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Adaptive evolution of voltage-gated sodium channels: The first 800 million years.
H. H. Zakon (2012)
PNAS 109, 10619-10625
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882