CLONING AND FUNCTIONAL EXPRESSION OF A DROSOPHILA GAMMA-AMINOBUTYRIC-ACID RECEPTOR

A cDNA encoding a functional gamma-aminobutyric (GABA)-activated Cl- c hannel has been isolated from an adult Drosophila head cDNA library. W hen expressed in Xenopus laevis oocytes, the subunit functions efficie ntly, presumably as a homooligomeric complex and is activated by GABA or muscimol. GABA-evoked currents are highly sensitive to antagonism b y picrotoxin but are insensitive to bicuculline, RU 5135, or zinc. Pen tobarbitone greatly enhances GABA-evoked currents, whereas the neurost eroid 5 alpha-pregnan-3 alpha-ol-20-one demonstrates a large reduction in both tbe 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 recepto rs formed by this subunit exhibit a unique pharmacology when compared with vertebrate GABA type A receptors or those composed of rho subunit s. Because the receptor-channel complex functions as a homooligomer, t his subunit may be of value in mutagenesis studies aiming to define dr ug-binding sites.