TY  - JOUR
A1  - Lu, Ruirui
A1  - Metzner, Katharina
A1  - Zhou, Fangyuan
A1  - Flauaus, Cathrin
A1  - Balzulat, Annika
A1  - Engel, Patrick
A1  - Petersen, Jonas
A1  - Ehinger, Rebekka
A1  - Bausch, Anne
A1  - Ruth, Peter
A1  - Lukowski, Robert
A1  - Schmidtko, Achim
T1  - Functional coupling of Slack channels and P2X3 receptors contributes to neuropathic pain processing
T2  - International Journal of Molecular Sciences
N2  - 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.
KW  - Slack
KW  - P2X3
KW  - dorsal root ganglia
KW  - neuropathic pain
KW  - mice
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/57481
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-574811
SN  - 1422-0067
SN  - 1661-6596
N1  - 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)).
VL  - 22
IS  - Nr. 405
PB  - MDPI
CY  - Basel
ER  -