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

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.

Name dc:type.qualificationname

phd

Level dc:type.qualificationlevel

doctoral

Grantor dc:publisher.institution

Nottingham Trent University

Year dc:date.issued

2010

Author dc:creator

• Schwabe, T

Language dc:language

en