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.
|Number of pages||5|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|Publication status||Published - 21 Jun 1994|