Functional coupling of Slack channels and P2X3 receptors contributes to neuropathic pain processing

  • The sodium-activated potassium channel Slack (KNa1.1, Slo2.2, or Kcnt1) is highly expressed in populations of sensory neurons, where it mediates the sodium-activated potassium current (IKNa) and modulates neuronal activity. Previous studies suggest that Slack is involved in the processing of neuropathic pain. However, mechanisms underlying the regulation of Slack activity in this context are poorly understood. Using whole-cell patch-clamp recordings we found that Slack-mediated IKNa in sensory neurons of mice is reduced after peripheral nerve injury, thereby contributing to neuropathic pain hypersensitivity. Interestingly, Slack is closely associated with ATP-sensitive P2X3 receptors in a population of sensory neurons. In vitro experiments revealed that Slack-mediated IKNa may be bidirectionally modulated in response to P2X3 activation. Moreover, mice lacking Slack show altered nocifensive responses to P2X3 stimulation. Our study identifies P2X3/Slack signaling as a mechanism contributing to hypersensitivity after peripheral nerve injury and proposes a potential novel strategy for treatment of neuropathic pain.

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Author:Ruirui LuGND, Katharina Metzner, Fangyuan ZhouORCiDGND, Cathrin FlauausGND, Annika Balzulat, Patrick Engel, Jonas Petersen, Rebekka EhingerGND, Anne Bausch, Peter RuthGND, Robert Lukowski, Achim SchmidtkoORCiDGND
Parent Title (English):International Journal of Molecular Sciences
Place of publication:Basel
Document Type:Article
Date of Publication (online):2021/01/02
Date of first Publication:2021/01/02
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2021/01/04
Tag:P2X3; Slack; dorsal root ganglia; mice; neuropathic pain
Issue:Nr. 405
Page Number:18
This research was funded by the Else Kröner-Fresenius-Stiftung (2018_A95 to A.S.) and theDeutsche Forschungsgemeinschaft (LU 2514/1-1 to R.L. (Ruirui Lu)).
Institutes:Biochemie, Chemie und Pharmazie / Pharmazie
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0