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Slack Potassium Channels Modulate TRPA1-Mediated Nociception in Sensory Neurons.
Zhou, Fangyuan; Metzner, Katharina; Engel, Patrick; Balzulat, Annika; Sisignano, Marco; Ruth, Peter; Lukowski, Robert; Schmidtko, Achim; Lu, Ruirui.
Afiliação
  • Zhou F; Institute of Pharmacology and Clinical Pharmacy, Goethe University, 60438 Frankfurt am Main, Germany.
  • Metzner K; Institute of Pharmacology and Clinical Pharmacy, Goethe University, 60438 Frankfurt am Main, Germany.
  • Engel P; Institute of Pharmacology and Clinical Pharmacy, Goethe University, 60438 Frankfurt am Main, Germany.
  • Balzulat A; Institute of Pharmacology and Clinical Pharmacy, Goethe University, 60438 Frankfurt am Main, Germany.
  • Sisignano M; Institute of Clinical Pharmacology, Pharmazentrum Frankfurt/ZAFES, Goethe University, 60590 Frankfurt am Main, Germany.
  • Ruth P; Department of Pharmacology, Toxicology and Clinical Pharmacy, University of Tübingen, 72076 Tübingen, Germany.
  • Lukowski R; Department of Pharmacology, Toxicology and Clinical Pharmacy, University of Tübingen, 72076 Tübingen, Germany.
  • Schmidtko A; Institute of Pharmacology and Clinical Pharmacy, Goethe University, 60438 Frankfurt am Main, Germany.
  • Lu R; Institute of Pharmacology and Clinical Pharmacy, Goethe University, 60438 Frankfurt am Main, Germany.
Cells ; 11(10)2022 05 19.
Article em En | MEDLINE | ID: mdl-35626730
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Canais de Potencial de Receptor Transitório / Nociceptividade Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Canais de Potencial de Receptor Transitório / Nociceptividade Idioma: En Ano de publicação: 2022 Tipo de documento: Article