title: Thalamic Kv 7 channels: pharmacological properties and activity control during noxious signal processing.
abstract: OBJECTIVE
  The existence of functional K(v)7 channels in thalamocortical (TC) relay neurons and the effects of the K(+)-current termed M-current (I(M)) on thalamic signal processing have long been debated. Immunocytochemical evidence suggests their presence in this brain region. Therefore, we aimed to verify their existence, pharmacological properties and function in regulating activity in neurons of the ventrobasal thalamus (VB).
  
  
  METHODS
  Characterization of K(v)7 channels was performed by combining in vitro, in vivo and in silico techniques with a pharmacological approach. Retigabine (30 μM) and XE991 (20 μM), a specific K(v)7 channel enhancer and blocker, respectively, were applied in acute brain slices during electrophysiological recordings. The effects of intrathalamic injection of retigabine (3 mM, 300 nL) and/or XE991 (2 mM, 300 nL) were investigated in freely moving animals during hot-plate tests by recording behaviour and neuronal activity.
  
  
  RESULTS
  K(v)7.2 and K(v)7.3 subunits were found to be abundantly expressed in TC neurons of mouse VB. A slow K(+)-current with properties of IM was activated by retigabine and inhibited by XE991. K(v)7 channel activation evoked membrane hyperpolarization, a reduction in tonic action potential firing, and increased burst firing in vitro and in computational models. Single-unit recordings and pharmacological intervention demonstrated a specific burst-firing increase upon I(M) activation in vivo. A K(v)7 channel-mediated increase in pain threshold was associated with fewer VB units responding to noxious stimuli, and increased burst firing in responsive neurons.
  
  
  CONCLUSIONS
  K(v)7 channel enhancement alters somatosensory activity and may reflect an anti-nociceptive mechanism during acute pain processing.
authors: Institute of Physiology I, Westfälische Wilhelms-University, Münster, Germany.
authors: Manuela
authors: M
authors: Cerina
authors: Institute of Physiology I, Westfälische Wilhelms-University, Münster, Germany.
authors: Hanna J
authors: HJ
authors: Szkudlarek
authors: Institute of Physiology I, Westfälische Wilhelms-University, Münster, Germany.
authors: Philippe
authors: P
authors: Coulon
authors: Institute of Physiology I, Westfälische Wilhelms-University, Münster, Germany.|Department of Neurology, Westfälische Wilhelms-University, Münster, Germany.
authors: Patrick
authors: P
authors: Meuth
authors: Institute of Physiology I, Westfälische Wilhelms-University, Münster, Germany.
authors: Tatyana
authors: T
authors: Kanyshkova
authors: Institute of Physiology I, Westfälische Wilhelms-University, Münster, Germany.
authors: Xuan Vinh
authors: XV
authors: Nguyen
authors: Department of Neurology, Westfälische Wilhelms-University, Münster, Germany.
authors: Kerstin
authors: K
authors: Göbel
authors: Institute of Physiology I, Westfälische Wilhelms-University, Münster, Germany.
authors: Thomas
authors: T
authors: Seidenbecher
authors: Department of Neurology, Westfälische Wilhelms-University, Münster, Germany.|Institute of Physiology-Neuropathophysiology, Westfälische Wilhelms-University, Münster, Germany.
authors: Sven G
authors: SG
authors: Meuth
authors: Institute of Physiology I, Westfälische Wilhelms-University, Münster, Germany.
authors: Hans-Christian
authors: HC
authors: Pape
authors: Institute of Physiology I, Westfälische Wilhelms-University, Münster, Germany.
authors: Thomas
authors: T
authors: Budde
mesh_terms: D000200:Action Potentials; D059787:Acute Pain / Q000503:physiopathology*; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002219:Carbamates / Q000494:pharmacology; D004195:Disease Models, Animal; D051656:KCNQ Potassium Channels / Q000378:metabolism*; D051658:KCNQ2 Potassium Channel / Q000378:metabolism; D051659:KCNQ3 Potassium Channel / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects; D017288:Pain Threshold / Q000502:physiology; D010655:Phenylenediamines / Q000494:pharmacology; D013788:Thalamus / Q000187:drug effects* / Q000378:metabolism
chemical_list: C112297:10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone; D000873:Anthracenes; D002219:Carbamates; D051656:KCNQ Potassium Channels; D051658:KCNQ2 Potassium Channel; D051659:KCNQ3 Potassium Channel; D010655:Phenylenediamines; C101866:ezogabine