Cloning and functional expression of a Drosophila gamma-aminobutyric acid receptor

Runtian Chen, Delia Belelli, Jeremy J. Lambert, John A. Peters, Antonio Reyes, Nancy C. Lan

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

A cDNA encoding a functional γ-aminobutyric (GABA)-activated Cl- channel has been isolated from an adult Drosophila head cDNA library. When expressed in Xenopus laevis oocytes, the subunit functions efficiently, presumably as a homooligomeric complex and is activated by GABA or muscimol. GABA-evoked currents are highly sensitive to antagonism by picrotoxin but are insensitive to bicuculline, RU 5135, or zinc. Pentobarbitone greatly enhances GABA- evoked currents, whereas the neurosteroid 5α-pregnan-3α-ol-20-one demonstrates a large reduction in both the potency and maximal effect when compared with its actions upon vertebrate GABA type A receptors. Although zinc-insensitive, the subunit is also insensitive to flunitrazepam. Hence, the GABA receptors formed by this subunit exhibit a unique pharmacology when compared with vertebrate GABA type A receptors or those composed of ρ subunits. Because the receptor-channel complex functions as a homooligomer, this subunit may be of value in mutagenesis studies aiming to define drug- binding sites.

Original languageEnglish
Pages (from-to)6069-6073
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number13
DOIs
Publication statusPublished - 21 Jun 1994

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