Investigation of an unusual GABA-A receptor: studies on the promiscuous ε [epsilon] subunit

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Schwabe, T, 2010. Investigation of an unusual GABA-A receptor: studies on the promiscuous ε [epsilon] subunit. PhD, Nottingham Trent University.

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Abstract

γ-aminobutyric acid (GABA) type A (GABAA) receptors are pentameric, chloride-selective ion channels. Nineteen different GABAA receptor subunits are known to exist in man and various subunit combinations are able to form receptor subtypes with different, subunit-specific pharmacological properties. GABAA receptors are targeted by many clinically-important drugs, for example, benzodiazepines. Unwanted side effects, such as tolerance and dependence, often occur due to non-selective receptor targeting. There is, therefore, a need for subtype-selective drugs. Comparatively little is known about the role of the ε subunit or ε-subunit-containing receptors in vivo. Recently, it has been recognised that a GABAA receptor subtype, that contains the α3 and ε subunits, is present in neurons within the forebrain that synthesise acetylcholine, and this may regulate neurotransmitter release. In Alzheimer’s disease, cholinergic neurotransmission is reduced; therefore, this subtype might be a target for the development of anti-Alzheimer’s disease drugs that would function by increasing acetylcholine release in forebrain regions where cholinergic neurons are dying. The pharmacological properties of a GABAA receptor that comprises the α3, β2 and ε subunits were examined in Xenopus laevis oocytes using the two-electrode voltage-clamp technique. The results obtained confirm that the ε subunit confers unusual properties on the GABAA receptor.

Item Type:	Thesis
Creators:	Schwabe, T.
Publisher:	Nottingham Trent University
Place of Publication:	Nottingham
Date:	2010
Rights:	This work is the intellectual property of the author, and may also be owned by Nottingham Trent University. You may copy up to 5% of this work for private study, or personal, non-commercial research. Any re-use of the information contained within this document should be fully referenced, quoting the author, title, university, degree level and pagination. Queries or requests for any other use, or if a more substantial copy is required, should be directed in the first instance to the author.
Divisions:	Schools > School of Science and Technology
Record created by:	EPrints Services
Date Added:	09 Oct 2015 09:34
Last Modified:	09 Oct 2015 09:34
URI:	https://irep.ntu.ac.uk/id/eprint/197