Current potentiation by diazepam but not GABA sensitivity is determined by a single histidine residue

Item Type:	Article
Title:	Current potentiation by diazepam but not GABA sensitivity is determined by a single histidine residue
Creators Name:	Kleingoor, C. and Wieland, H. and Korpi, E.R. and Seeburg, P.H. and Kettenmann, H.
Abstract:	The GABAA/benzodiazepine receptor is the principal inhibitory neurotransmitter receptor in the mammalian brain and is assembled from sequence-related subunits, such as alpha 1 beta 2 gamma 2. In contrast to alpha 1 beta 2 gamma 2 receptors, alpha 6 beta 2 gamma 2 receptors fail to exhibit high-affinity binding of allosteric positive modulators of GABA-activated chloride currents. The critical determinant responsible for this difference in ligand binding was previously traced to a position in the extracellular domain of the two alpha subunits (alpha 1 His100 and alpha 6 Arg 101). We now show by patch clamp analysis that this amino acid exchange also determines the diazepam potentiation. Thus, alpha 1(Arg101)beta 2 gamma 2 receptors do not, but alpha 6(His100)beta 2 gamma 2 receptors do exhibit diazepam potentiation. However, the same extracellular determinant is not responsible for the increased GABA sensitivity of alpha 6 beta 2 gamma 2 receptors relative to alpha 1 beta 2 gamma 2 receptors as revealed by electrophysiological analysis and by differential GABA sensitivity of [35S]TBPS binding.
Keywords:	GABA Receptor, Benzodiazepines, Patch Clamp, Recombinant Receptors, Cell Transfection
Source:	NeuroReport
ISSN:	0959-4965
Publisher:	Lippincott Williams & Wilkins
Volume:	4
Number:	2
Page Range:	187-190
Date:	1 February 1993
PubMed:	View item in PubMed

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