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A Draguhn

Publications and source records attributed to A Draguhn.

40 records · Page 3Linked to original sources

Functional and molecular distinction between recombinant rat GABAA receptor subtypes by Zn2+.

gamma-Aminobutyric acid receptor (GABAAR) channels in different neurons display heterogeneous functional properties. Molecular cloning revealed a large number of GABAAR subunits that assemble into GABAAR subtypes with different functional properties, suggesting that the subunit combination determines the functional properties of the receptor. In this study, the subunit composition of GABAARs is related to a functional distinction between Zn2(+)-sensitive and Zn2(+)-insensitive receptor subtypes. GABAARs reconstituted in transiently transfected fibroblasts from combinations of cDNAs encoding alpha and beta subunits are potently blocked by Zn2+. The presence of a gamma subunit in any combination with the other subunits leads to the formation of GABAARs that are almost insensitive to Zn2+. These data provide a structural correlate to the functional heterogeneity of the action of Zn2+ on GABAARs in native membranes and show that Zn2+ insensitivity of GABA-activated currents indicates the presence of a gamma-subunit in the assembled GABAAR channel.

Animals↗

Sequence and expression of a novel GABAA receptor alpha subunit.

Cloned cDNA encoding the bovine alpha 4 subunit of the GABAA receptor has been isolated. The predicted 51 amino acid long mature protein contains an exceptionally long intracellular domain and shares 53-56% sequence similarity to the previously characterized alpha 1, alpha 2 and alpha 3 subunits. Co-expression of alpha 4 and beta 1 in Xenopus oocytes resulted in the formation of GABA-gated chloride channels with expected pharmacology, although no benzodiazepine potentiation was observed. Northern analysis indicates that a 4 kb alpha 4 mRNA is expressed in the calf cerebellum, cortex and hippocampus but is barely detectable in the rat brain.

Animals↗

GABAA receptor beta subunit heterogeneity: functional expression of cloned cDNAs.

Cloned cDNAs encoding two new beta subunits of the rat and bovine GABAA receptor have been isolated using a degenerate oligonucleotide probe based on a highly conserved peptide sequence in the second transmembrane domain of GABAA receptor subunits. The beta 2 and beta 3 subunits share approximately 72% sequence identity with the previously characterized beta 1 polypeptide. Northern analysis showed that both beta 2 and beta 3 mRNAs are more abundant in the brain than beta 1 mRNA. All three beta subunit encoding cDNAs were also identified in a library constructed from adrenal medulla RNA. Each beta subunit, when co-expressed in Xenopus oocytes with an alpha subunit, forms functional GABAA receptors. These results, together with the known alpha subunit heterogeneity, suggest that a variety of related but functionally distinct GABAA receptor subtypes are generated by different subunit combinations.

Adrenal Medulla↗