Triton x-100 inhibits agonist-induced currents and suppresses benzodiazepine modulation of GABAA receptors in Xenopus oocytes

Changes in lipid bilayer elastic properties have been proposed to underlie the modulation of voltage-gated Na+ and L-type Ca2+ channels and GABAA receptors by amphiphiles. The amphiphile Triton X-100 increases the elasticity of lipid bilayers at micromolar concentrations, assessed from its effects on gramicidin channel A appearance rate and lifetime in artificial lipid bilayers. In the present study, the pharmacological action of Triton-X 100 on GABAA receptors expressed in Xenopus laevis oocytes was examined. Triton-X 100 inhibited GABAA α1β3γ2S receptor currents in a noncompetitive, time- and voltage-dependent manner and increased the apparent rate and extent of desensitization at 10 μM, which is 30 fold below the critical micelle concentration. In addition, Triton X-100 induced picrotoxin-sensitive GABAA receptor currents and suppressed allosteric modulation by flunitrazepam at α1β3γ2S receptors. All effects were independent of the presence of a γ2S subunit in the GABAA receptor complex. The present study suggests that Triton X-100 may stabilize open and desensitized states of the GABAA receptor through changes in lipid bilayer elasticity.