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Papers of the Week

Papers: 2 Jan 2021 - 8 Jan 2021

Animal Studies

2021 Jan 02

Int J Mol Sci



Functional Coupling of Slack Channels and P2X3 Receptors Contributes to Neuropathic Pain Processing.


Lu R, Metzner K, Zhou F, Flauaus C, Balzulat A, Engel P, Petersen J, Ehinger R, Bausch A, Ruth P, Lukowski R, Schmidtko A
Int J Mol Sci. 2021 Jan 02; 22(1).
PMID: 33401689.


The sodium-activated potassium channel Slack (K1.1, Slo2.2, or Kcnt1) is highly expressed in populations of sensory neurons, where it mediates the sodium-activated potassium current (I) 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 I 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 I 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.