Question: 

KCNQ channels are the molecular substrate of the slow voltage-activated delayed rectifier type K⁺ current termed I_M. This current operates below action potential threshold and effectively limits neuronal excitability. Recently, we detected the mRNA and protein expression of KCNQ2 and KCNQ3 in the somatosensory ventrobasal thalamic complex (VB). To determine the contribution of KCNQ channels to thalamic activity modes and to analyse their possible role in somatosensory and noxious stimulus processing, VB neurons were recorded in vitro.

Methods: 

Whole-cell patch-clamp recordings were performed in thalamocortical relay (TC) neurons in brain slices. Moreover, behavioural analysis of mice during acute pain stimulation in hot plate experiments has been performed.

Results: 

TC neurons generated a slow K⁺ outward current component, which was enhanced and inhibited by specific KCNQ channel openers (retigabine) and inhibitors (XE991), respectively. Furthermore, this current component was inhibited by muscarinic agonists (OxoM) and enhanced by neuropeptides (dynorphine A, nociceptin). In current-clamp recordings retigabine reduced burst and tonic firing of TC neurons. During hot plate, testing intrathalamic injection of retigabine and XE991 significantly increased and decreased the latency to the occurrence of aversive behaviour, respectively. Furthermore, the anti-nociceptive effect of retigabine was completely removed by co-injection of XE991.

Conclusions: 

These findings indicate that VB TC neurons generate I_M, which modulates cellular excitability by inducing spike frequency adaptation and may play an important role in limiting animal responses to acute pain stimuli. Both effects may depend on I_M stimulation by endogenous neuropeptides.