Vol. 282, Issue 3, 1557-1564, 1997

The Interactions of Hexachlorocyclohexane Isomers with Human -Aminobutyric Acid_A Receptors Expressed in Xenopus Oocytes

L. S. Aspinwall¹ , I. Bermudez, L. A. King and K. A. Wafford

School of Biological and Molecular Sciences, Oxford Brookes University, Gipsy Lane Campus, Oxford, OX3 0BP (L.S.A., I.B., L.A.K.) and Merck Sharp & Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex, CM20 2QR (K.A.W.)

The effects of -hexachlorocyclohexane (-HCH) and its ,  and  isomers on the -aminobutyric acid (GABA) responses of human 132S and 632S GABA_A receptors expressed in Xenopus oocytes were examined by conventional two-electrode voltage-clamp techniques. -HCH induced partial inhibition of EC₅₀ GABA responses, whereas the  and  isomers produced potentiation of EC₂₀ GABA currents. In contrast, -HCH had no effect on GABA currents, even at concentrations as high as 100 µM. The effects of the active HCH isomers were not influenced by alpha subunit composition because there was no significant difference in either the inhibition or potentiation of 132S or 632S GABA_A receptors. - and -HCH antagonized picrotoxin inhibition and caused displacement of specific [³⁵S]t-butylbicyclophosphorothionate binding. -HCH potentiation was found to be additive with steroid, loreclezole and lanthanum potentiation, but nonadditive with potentiation by pentobarbital and propofol, which suggested that its activity was linked to the barbiturate site.