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bioRxiv · 10.1101/2020.09.11.293423

The KCNQ4-mediated M-current regulates the circadian rhythm in mesopontine cholinergic neurons

Tsogbadrakh, B.·Stupniki, S.·Kovacs, A.·Csemer, A.·Szentesi, P.·Pocsai, K.·Dionisio, L.·Spitzmaul, G.·Pal, B.
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Abstract

The M-current is a voltage gated potassium current inhibited by muscarinic activation and affected by several other G-protein coupled receptors. Its channels are formed by KCNQ subunits, from which KCNQ4 is restricted to certain brainstem structures. We sought evidence for the function of the M-current in the pedunculopontine nucleus (PPN) and the contribution of KCNQ4 subunits to the M-current and aimed to find its functional significance in the PPN. We found that cholinergic inputs of the PPN can effectively inhibit M-current. This current is capable of synchronizing neighboring neurons and inhibition of the M-current decreases neuronal synchronization. We showed that only a subpopulation of cholinergic neurons has KCNQ4-dependent M-current. The KCNQ4 subunit expression potentially regulates the presence of other KCNQ subunits. Deletion of KCNQ4 leads to alterations in adaptation of activity to light-darkness cycles, thus representing the potential role of KCNQ4 in regulation of sleep-wakefulness cycles. The presence of this protein restricted to certain brainstem nuclei raises the possibility that it might be a potential target for selective therapeutic interventions affecting the reticular activating system.

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Tsogbadrakh, B., Stupniki, S., Kovacs, A., Csemer, A., Szentesi, P., Pocsai, K., Dionisio, L., Spitzmaul, G., Pal, B.. 2020-09-12. The KCNQ4-mediated M-current regulates the circadian rhythm in mesopontine cholinergic neurons. https://doi.org/10.1101/2020.09.11.293423

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