POSITIVE MODULATION OF HUMAN GAMMA-AMINOBUTYRIC-ACID TYPE-A AND GLYCINE RECEPTORS BY THE INHALATION ANESTHETIC ISOFLURANE

The interactions of the inhalation anesthetic agent isoflurane with li gand-gated chloride channels were studied using transient expression o f recombinant human receptors in a mammalian cell line. Isoflurane enh anced gamma-aminobutyric acid (GABA)-activated chloride currents in ce lls that expressed heteromeric GABA(A) receptors consisting of combina tions of alpha1 or alpha2, beta1, and gamma2 subunits and in cells tha t expressed receptors consisting of combinations of only alpha and bet a subunits. Receptors consisting of alpha2 and gamma2 subunits were po orly expressed but were sensitive to isoflurane. Receptors consisting of beta1 and gamma2 subunits were not expressed. Isoflurane also enhan ced glycine-activated chloride currents through homomeric alpha glycin e receptors but did not enhance GABA currents in cells expressing homo meric rho1 receptors. These results show that not all ligand-gated chl oride channel receptors are sensitive to isoflurane and, therefore, th at the anesthetic interacts with specific structural determinants of t hese ion channel proteins.