Kinetic analyses of alcohol-induced potentiation of the response of GABA(A) receptors composed of alpha(1) and beta(1) subunits

To investigate the kinetics of both the potentiation and desensitization of the response of ionotropic GABA receptors (GABA., receptors) in the presen ce of various compounds, we expressed receptors composed of alpha (1) and b eta (1) subunits by injecting cells with the cRNAs synthesized from cloned bovine GABA, receptor cDNAS and measured the electrical responses of the ce lls electrophysiologically with or without the compounds. The potentiation of the GABA, receptor-mediated response was quantitatively analyzed using a simple model with the assumption that the receptors have two identical bin ding sites for GABA molecules with a dissociation constant of K-1, and one potentiation site for the compound with a dissociation constant of K-p, and that the binding of the compound to the potentiation site only increases t he affinity of the GABA binding sites, changing K-1 to K-1p. The estimated K-p and K-1p were dependent on the functional groups and the chain length o f the compounds. These results could be satisfactorily analyzed using this simple model. The potentiation of the GABAA receptor-mediated response by t he components of essential oils used for aromatherapy was also examined. Th ese compounds accelerated the decay of the response, possibly due to desens itization of the receptors, which was also analyzed on the basis of the mod el.