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BRIEF RESEARCH REPORT article

Front. Pharmacol.
Sec. Neuropharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1459735
This article is part of the Research Topic Pain and Pain-Related Neuropsychiatric Disorders: From Mechanistic Insights to Innovative Therapeutic Strategies View all 14 articles

Slick potassium channels limit TRPM3-mediated activation of sensory neurons

Provisionally accepted
Patrick Engel Patrick Engel Fangyuan Zhou Fangyuan Zhou Bang Tam Thi Tran Bang Tam Thi Tran Achim Schmidtko Achim Schmidtko Ruirui Lu Ruirui Lu *
  • Institute of Pharmacology and Clinical Pharmacy, Goethe University Frankfurt, Frankfurt, Germany

The final, formatted version of the article will be published soon.

    Heat sensation is mediated by specialized heat-sensitive neurons in the somatosensory system that innervates the skin. Previous studies revealed that noxious heat sensation is controlled by the sodium (Na + )-activated potassium (K + ) channel Slick (Kcnt2), which is highly expressed in nociceptive Aδfibers. However, the mechanism by which Slick modulates heat sensation is poorly understood. Here, we generated mice lacking Slick conditionally in sensory neurons expressing Nav1.8 (SNS-Slick -/- mice). In SNS-Slick -/-mice, the latency to express any nocifensive behavior was reduced in the hot plate and tail immersion tests. In situ hybridization experiments revealed Slick was highly co-expressed with the essential heat sensor, transient receptor potential (TRP) melastatin (TRPM) 3, but not with TRP vanilloid 1, TRP ankyrin 1, or TRPM2 in sensory neurons. Notably, SNS-Slick -/-mice exhibited increased nocifensive behaviors following the intraplantar injection of the TRPM3 activator pregnenolone sulfate. Patch-clamp recordings detected increased Na + -dependent outward K + current (IK) after TRPM3 activation in sensory neurons, which showed no prominent IK after the replacement of NaCl with choline chloride. Thus, our study suggests that Slick limits TRPM3-mediated activation of sensory neurons, thereby inhibiting noxious heat sensing.

    Keywords: Heat nociception1, TRPM32, Slick3, sensory neurons4, potassium current5

    Received: 04 Jul 2024; Accepted: 26 Nov 2024.

    Copyright: © 2024 Engel, Zhou, Tran, Schmidtko and Lu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Ruirui Lu, Institute of Pharmacology and Clinical Pharmacy, Goethe University Frankfurt, Frankfurt, Germany

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.