TY  - JOUR
A1  - Zhou, Fangyuan
A1  - Metzner, Katharina
A1  - Engel, Patrick
A1  - Balzulat, Annika
A1  - Sisignano, Marco
A1  - Ruth, Peter
A1  - Lukowski, Robert
A1  - Schmidtko, Achim
A1  - Lu, Ruirui
T1  - Slack potassium channels modulate TRPA1-mediated nociception in sensory neurons
T2  - Cells
N2  - 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.
Keywords: TRPA1; slack; dorsal root ganglia; pain; mice
Y1  - 2022
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/74332
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-743328
SN  - 2073-4409
VL  - 11
IS  - 10
PB  - MDPI
CY  - Basel
ER  -