Effects of volatile anesthetics and a volatile convulsant on human recombinant γ-aminobutyric acid (GABA) type A receptor responses were studied using the whole cell configuration of the patch clamp technique. Sf9 cells were transfected with bacuroviruses carrying cDNAs of α1β2, α1β2γ2s, α3β2 and α3β2γ2s subunit combinations of the human GABA(A) receptor. Clinical concentrations of isoflurane (a volatile anesthetic) enhanced the GABA-induced current of the α1β2γ2s and α3β2γ2s GABA(A) subunit combinations. On the other hand, isoflurane suppressed the current of the α1β2 and α3β2 subunit combinations, indicating that the anesthetic effects depended upon the presence of γ2s subunit. A high concentration (2 mM) of isoflurane generated a surge current following the washout of GABA and the anesthetic. Hexafluorodiethyl ether (a volatile convulsant) decreased the GABA-response of the both α3β2γ2s and α3β2 constructs without generating a surge current. The results suggest that volatile agents affect the receptor-ionophore complex via direct interaction with proteins but not through a perturbation of the membrane lipid environment. A hypothetical sequential model for the anesthetic action is presented. Copyright (C) 1999 Elsevier Science B.V.
- Anesthetic, volatile
- Convulsant, volatile
- GABA(A) receptor, recombinant
- Sf9 cell
ASJC Scopus subject areas