Halothane acts as a partial agonist of the α6β2γ2S GABA(A) receptor

Whole-cell patch clamp recording was performed on human embryonic kidney 293 cells stably transfected with rat cDNAs for the α6, β2, and γ2S subunits of the GABA(A) receptor. The volatile anesthetic halothane directly activated a current in the absence of the ligand γ-aminobutyric acid (GABA). Both the current amplitude and the rate of desensitization increased in a dose-dependent manner with an EC₅₀ of 1.0±0.2 mM and a Hill coefficient (n(h)) of 1.5±0.1. The EC₅₀ and n(h) for GABA to activate the receptor were 1.0±0.3 μM and 1.4±0.2, respectively. The peak amplitude of the halothane-activated current was about 4% of the maximal GABA response, which was not changed when the concentration of Ca²⁺ in the external solution was decreased from 2 mM to 0.2 mM. The reversal potential of both halothane- and GABA-activated currents changed with the external Cl^- concentration as predicted by the Nernst equation for chloride ions. The halothane- and GABA- activated currents were blocked by both the noncompetitive GABA(A) receptor antagonist picrotoxin and the competitive GABA(A) receptor antagonist bicuculline. Schild plots revealed that the K(i)s for bicuculline to competitively antagonize the currents activated by halothane and GABA are similar (0.69 and 0.72 μM, respectively). These results indicate that halothane activates the α6β2γ2S GABA(A) receptor to induce a current similar to the GABA-induced current.