PMID- 35626730
OWN - NLM
STAT- MEDLINE
DCOM- 20220531
LR  - 20220716
IS  - 2073-4409 (Electronic)
IS  - 2073-4409 (Linking)
VI  - 11
IP  - 10
DP  - 2022 May 19
TI  - Slack Potassium Channels Modulate TRPA1-Mediated Nociception in Sensory Neurons.
LID - 10.3390/cells11101693 [doi]
LID - 1693
AB  - 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 (K(Na)1.1, 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 (I(KS)) 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.
FAU - Zhou, Fangyuan
AU  - Zhou F
AUID- ORCID: 0000-0002-5620-6775
AD  - Institute of Pharmacology and Clinical Pharmacy, Goethe University, 60438 
      Frankfurt am Main, Germany.
FAU - Metzner, Katharina
AU  - Metzner K
AD  - Institute of Pharmacology and Clinical Pharmacy, Goethe University, 60438 
      Frankfurt am Main, Germany.
FAU - Engel, Patrick
AU  - Engel P
AD  - Institute of Pharmacology and Clinical Pharmacy, Goethe University, 60438 
      Frankfurt am Main, Germany.
FAU - Balzulat, Annika
AU  - Balzulat A
AD  - Institute of Pharmacology and Clinical Pharmacy, Goethe University, 60438 
      Frankfurt am Main, Germany.
FAU - Sisignano, Marco
AU  - Sisignano M
AUID- ORCID: 0000-0002-7581-0951
AD  - Institute of Clinical Pharmacology, Pharmazentrum Frankfurt/ZAFES, Goethe 
      University, 60590 Frankfurt am Main, Germany.
FAU - Ruth, Peter
AU  - Ruth P
AD  - Department of Pharmacology, Toxicology and Clinical Pharmacy, University of 
      Tubingen, 72076 Tubingen, Germany.
FAU - Lukowski, Robert
AU  - Lukowski R
AD  - Department of Pharmacology, Toxicology and Clinical Pharmacy, University of 
      Tubingen, 72076 Tubingen, Germany.
FAU - Schmidtko, Achim
AU  - Schmidtko A
AUID- ORCID: 0000-0001-7270-5075
AD  - Institute of Pharmacology and Clinical Pharmacy, Goethe University, 60438 
      Frankfurt am Main, Germany.
FAU - Lu, Ruirui
AU  - Lu R
AD  - Institute of Pharmacology and Clinical Pharmacy, Goethe University, 60438 
      Frankfurt am Main, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220519
PL  - Switzerland
TA  - Cells
JT  - Cells
JID - 101600052
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Potassium Channels)
RN  - 0 (Potassium Channels, Sodium-Activated)
RN  - 0 (Slo2 protein, mouse)
RN  - 0 (TRPA1 Cation Channel)
RN  - 0 (Transient Receptor Potential Channels)
RN  - 0 (Trpa1 protein, mouse)
SB  - IM
MH  - Animals
MH  - Mice
MH  - Nerve Tissue Proteins/genetics/metabolism
MH  - *Nociception
MH  - Pain/metabolism
MH  - Potassium Channels/metabolism
MH  - Potassium Channels, Sodium-Activated
MH  - Sensory Receptor Cells/metabolism
MH  - TRPA1 Cation Channel/metabolism
MH  - *Transient Receptor Potential Channels/metabolism
PMC - PMC9140117
OTO - NOTNLM
OT  - TRPA1
OT  - dorsal root ganglia
OT  - mice
OT  - pain
OT  - slack
COIS- The authors declare no conflict of interest.
EDAT- 2022/05/29 06:00
MHDA- 2022/06/01 06:00
PMCR- 2022/05/19
CRDT- 2022/05/28 01:13
PHST- 2022/02/25 00:00 [received]
PHST- 2022/05/15 00:00 [revised]
PHST- 2022/05/17 00:00 [accepted]
PHST- 2022/05/28 01:13 [entrez]
PHST- 2022/05/29 06:00 [pubmed]
PHST- 2022/06/01 06:00 [medline]
PHST- 2022/05/19 00:00 [pmc-release]
AID - cells11101693 [pii]
AID - cells-11-01693 [pii]
AID - 10.3390/cells11101693 [doi]
PST - epublish
SO  - Cells. 2022 May 19;11(10):1693. doi: 10.3390/cells11101693.