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TRESK is a key regulator of nocturnal suprachiasmatic nucleus dynamics and light adaptive responses

Lalic, Tatjana, Steponenaite, Aiste, Wei, Liting, Vasudevan, Sridhar R., Mathie, Alistair, Peirson, Stuart N., Lall, Gurprit S., Cader, M. Zameel (2020) TRESK is a key regulator of nocturnal suprachiasmatic nucleus dynamics and light adaptive responses. Nature Communications, 11 . Article Number 4614. E-ISSN 2041-1723. (doi:10.1038/s41467-020-17978-9) (KAR id:82906)

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https://dx.doi.org/10.1038/s41467-020-17978-9

Abstract

The suprachiasmatic nucleus (SCN) is a complex structure dependent upon multiple mechanisms to ensure rhythmic electrical activity that varies between day and night, to determine circadian adaptation and behaviours. SCN neurons are exposed to glutamate from multiple sources including from the retino-hypothalamic tract and from astrocytes. However, the mechanism preventing inappropriate post-synaptic glutamatergic effects is unexplored and unknown. Unexpectedly we discovered that TRESK, a calcium regulated two-pore potassium channel, plays a crucial role in this system. We propose that glutamate activates TRESK through NMDA and AMPA mediated calcium influx and calcineurin activation to then oppose further membrane depolarisation and rising intracellular calcium. Hence, in the absence of TRESK, glutamatergic activity is unregulated leading to membrane depolarisation, increased nocturnal SCN firing, inverted basal calcium levels and impaired sensitivity in light induced phase delays. Our data reveals TRESK plays an essential part in SCN regulatory mechanisms and light induced adaptive behaviours.

Item Type: Article
DOI/Identification number: 10.1038/s41467-020-17978-9
Subjects: Q Science > QH Natural history > QH301 Biology
Q Science > QH Natural history > QH426 Genetics
Q Science > QP Physiology (Living systems) > QP506 Molecular biology
R Medicine
Divisions: Faculties > Sciences > Medway School of Pharmacy
Depositing User: Gurprit Lall
Date Deposited: 14 Sep 2020 10:29 UTC
Last Modified: 06 Oct 2020 09:44 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/82906 (The current URI for this page, for reference purposes)
Steponenaite, Aiste: https://orcid.org/0000-0002-1988-3419
Mathie, Alistair: https://orcid.org/0000-0001-6094-2890
Lall, Gurprit S.: https://orcid.org/0000-0003-3725-4795
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