Journal
BRITISH JOURNAL OF PHARMACOLOGY
Volume 172, Issue 12, Pages 3126-3140Publisher
WILEY
DOI: 10.1111/bph.13113
Keywords
-
Categories
Funding
- IZKF Munster [Bud3/010/10]
- DFG [BU1019/9-2 BU1019/11-1, SFB-TR128/B6]
- Max-Planck-Research Award
Ask authors/readers for more resources
Background and PurposeThe 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). Experimental ApproachCharacterization of K(v)7 channels was performed by combining in vitro, in vivo and in silico techniques with a pharmacological approach. Retigabine (30M) and XE991 (20M), 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 (3mM, 300nL) and/or XE991 (2mM, 300nL) were investigated in freely moving animals during hot-plate tests by recording behaviour and neuronal activity. Key ResultsK(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 I-M 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 and ImplicationsK(v)7 channel enhancement alters somatosensory activity and may reflect an anti-nociceptive mechanism during acute pain processing.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available