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. 2020 Jul 1;10:10730. doi: 10.1038/s41598-020-67761-5

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© The Author(s) 2020

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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The local anesthetics lidocaine and ambroxol differently modulate Na_V1.7 and NaChBac channel gating. (A) Chemical structures of four selected small molecule pore blockers, ambroxol, lidocaine, carbamazepine, and QX-314. Representative NaChBac current traces are shown before and after the application of compounds. Testing concentrations for the compounds are shown in Supplement Table I. (B) Lidocaine’s effect on the Na_V1.7 (top) and NaChBac (bottom) channels. Current traces (left), current–voltage (I–V) (middle), conductance–voltage (G–V), and steady-state inactivation (SSI) relationships are shown for both Na_V1.7 and NaChBac measured before and after application of 200 µM lidocaine. Lidocaine blocks both NaChBac and Na_V1.7 channels. (C) Ambroxol’s effect on Na_V1.7 (top) and NaChBac (bottom) channels. Representative current traces (left), I-V (middle), G–V, and SSI relationships (right) are shown for Na_V1.7 and NaChBac channels measured before and after 50 µM ambroxol. Ambroxol has similar effects as lidocaine on both Na_V1.7 and NaChBac.