Agonist and potentiation actions of n-octanol on γ-aminobutyric acid type A receptors

The n-octanol effects on the γ-aminobutyric acid type A (GABA(A)) receptor were studied in human embryonic kidney 293 cells transfected with α1, β2, and γ2S subunit cDNAs. GABA-evoked currents had an EC₅₀ of 13.3 ± 1.7 μM and a Hill coefficient (n(H)) of 1.4 ± 0.1. n-Octanol was also capable of evoking a small current with an EC₅₀ of 1000 μM and an n(H) of 2. In addition, n-octanol modulated GABA-induced currents in a concentration- dependent manner. Coapplications of n-octanol increased peak currents evoked by 3 μM GABA with an EC₅₀ of 190 μM and an n(H) of 1.8. The extent of potentiation decreased with increasing GABA concentrations and no potentiation was observed when n-octanol was coapplied with 1000 μM GABA. One-minute preapplication of 1000 μM n-octanol slightly potentiated 3 μM GABA-induced current, whereas it suppressed 300 μM GABA-induced current to 16% of the control, suggesting that 84% of the receptors underwent desensitization. Two models were used to explain n-octanol agonistic and potentiating actions on the α1β2γ2S GABA(A) receptor: n-octanol binds to multiple sites to exert multiple actions, or n-octanol acts as a partial agonist to manifest these actions. The partial agonist model is unique because iris a simpler model to explain n-octanol actions on the GABA(A) receptor.