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. 2017 Oct 6;7:12775. doi: 10.1038/s41598-017-13054-3

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© The Author(s) 2017

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Modulation of cysteines underlies the sensitization of TRPV1 by pBQ and NAPQI. (A,B) Mutation of internal cysteines in hTRPV1 abolishes sensitization of by both pBQ (G C158A/C391S/C767S-hTRPV1) and NAPQI (H C158A/C387S/C767S-hTRPV1). pBQ and both concentrations of NAPQI were applied for five minutes. These cysteines are also involved in sensitization of capsaicin- (C–F) and proton-induced (G–J) inward currents by both metabolites. Representative traces are displayed for pBQ (C and G, C158S/C391S/C767S-hTRPV1; (E and I) C158A/C387S/C767S-hTRPV1) and NAPQI (D and H), C158A/C387S/C767S-hTRPV1; F and J, C158S/C391S/C767S-hTRPV1). Bar diagrams show multiples of capsaicin- or proton-induced responses before and after application of pBQ (C and G) or NAPQI (D and H) in wild-type and mutant hTRPV1. Sensitization of capsaicin- and proton-induced responses was reduced for pBQ in C158A/C391S/C767S-hTRPV1 (*p ≤ 0.007), and completely lost for NAPQI in both mutants (*p ≤ 0.0009 respectively *p ≤ 0.005).