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The Role of TASK-3 Two-Pore Domain Potassium Channels in the Entrainment of Mammalian Circadian Rhythms

Atkinson, Lynsey A (2014) The Role of TASK-3 Two-Pore Domain Potassium Channels in the Entrainment of Mammalian Circadian Rhythms. Doctor of Philosophy (PhD) thesis, University of Kent,. (KAR id:47952)

Language: English
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In mammals light is the principal timing cue for alignment of physiology to the external environment. Illumination from the unrelenting 24-hour day-night cycle enters the biological system and is communicated to the master pacemaker, the suprachiasmatic nucleus (SCN) to drive circadian entrainment.

In the first experimental chapter I demonstrate the presence of TASK-3 mRNA in the SCN and retina of wild type mice. Further, I reveal a circadian pattern in TASK-3 mRNA expression with significant midday nadir which feasibly influences resting membrane potential (RMP) supporting increased neuronal excitation reported at this time.

With light entering the circadian system exclusively via the eyes, the role of TASK-3 at the level of the retina is of upmost importance to entrainment. This is investigated in chapter 6 using pupillary light reflex as a measure of retinal sensitivity and decoding capacity. Through manipulation of intensity and wavelength specific classes of photoreceptor are studied for their contribution to this non-image forming response. These experiments show TASK-3 ablation significantly attenuates retinal sensitivity to sub-saturating light in a mechanism likely to be melanopsin-independent.

Overall these experiments demonstrate some of the roles TASK-3 conductance plays within the SCN and in output rhythms; and the requirement of this channel within the retina for effective retinal decoding across the visible spectrum over a range of light intensities.

Item Type: Thesis (Doctor of Philosophy (PhD))
Thesis advisor: Lall, Gurprit
Thesis advisor: Mathie, Alistair
Uncontrolled keywords: TASK-3 ; Two-pore domain potassium channel ; Circadian entrainment ; suprachiasmatic nucleus (SCN) ; Locomotor activity ; Pupillary light reflex
Subjects: R Medicine > RM Therapeutics. Pharmacology
Divisions: Divisions > Division of Natural Sciences > Medway School of Pharmacy
Depositing User: Users 1 not found.
Date Deposited: 13 Apr 2015 10:01 UTC
Last Modified: 16 Feb 2021 13:24 UTC
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