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 and Cader, M Zameel (2020) TRESK is a key regulator of nocturnal suprachiasmatic nucleus dynamics and light adaptive responses. Nature communications, 11 (1). p. 4614. ISSN 2041-1723

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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
Uncontrolled Keywords: TRESK, suprachiasmatic nucleus dynamics
Subjects: Q Science > QP Physiology
Divisions: Faculty of Health & Science > Department of Science & Technology
Depositing User: Alistair Mathie
Date Deposited: 01 Mar 2021 11:03
Last Modified: 21 Sep 2021 10:47

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