Thalamic Kv 7 channels: pharmacological properties and activity control during noxious signal processing.

Cerina M; Szkudlarek HJ; Coulon P; Meuth P; Kanyshkova T; Nguyen XV; Göbel K; Seidenbecher T; Meuth SG; Pape HC; Budde T

Abstract

BACKGROUND AND PURPOSE - EXPERIMENTAL APPROACH - KEY RESULTS - CONCLUSIONS AND IMPLICATIONS; 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).; 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.; 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.; K(v)7 channel enhancement alters somatosensory activity and may reflect an anti-nociceptive mechanism during acute pain processing.