Slack potassium channels modulate TRPA1-mediated nociception in sensory neurons

  • The transient receptor potential (TRP) ankyrin type 1 (TRPA1) channel is highly expressed in a subset of sensory neurons where it acts as an essential detector of painful stimuli. However, the mechanisms that control the activity of sensory neurons upon TRPA1 activation remain poorly understood. Here, using in situ hybridization and immunostaining, we found TRPA1 to be extensively co-localized with the potassium channel Slack (KNa1.1, Slo2.2, or Kcnt1) in sensory neurons. Mice lacking Slack globally (Slack−/−) or conditionally in sensory neurons (SNS-Slack−/−) demonstrated increased pain behavior after intraplantar injection of the TRPA1 activator allyl isothiocyanate. By contrast, pain behavior induced by the TRP vanilloid 1 (TRPV1) activator capsaicin was normal in Slack-deficient mice. Patch-clamp recordings in sensory neurons and in a HEK cell line transfected with TRPA1 and Slack revealed that Slack-dependent potassium currents (IKS) are modulated in a TRPA1-dependent manner. Taken together, our findings highlight Slack as a modulator of TRPA1-mediated, but not TRPV1-mediated, activation of sensory neurons. Keywords: TRPA1; slack; dorsal root ganglia; pain; mice

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Author:Fangyuan ZhouORCiDGND, Katharina Metzner, Patrick Engel, Annika Balzulat, Marco SisignanoORCiDGND, Peter RuthGND, Robert Lukowski, Achim SchmidtkoORCiDGND, Ruirui LuGND
Parent Title (English):Cells
Place of publication:Basel
Document Type:Article
Date of Publication (online):2022/05/19
Date of first Publication:2022/05/19
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2023/07/11
Page Number:18
Institutes:Biochemie, Chemie und Pharmazie
Fachübergreifende Einrichtungen / Zentrum für Arzneimittelforschung, Entwicklung und Sicherheit
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0