Triton x-100 inhibits agonist-induced currents and suppresses benzodiazepine modulation of GABAA receptors in Xenopus oocytes |
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Authors: | Rikke Søgaard Bjarke Ebert Thomas Werge |
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Institution: | a Institute of Cellular and Molecular Medicine, Panum 12.6, University of Copenhagen, Blegdamsvej 3C, DK-2200, Copenhagen N, Denmark b Research Institute of Biological Psychiatry, St. Hans Hospital, Boserupvej 2, DK-4000 Roskilde, Denmark c Department of Electrophysiology, H. Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Denmark d Section for Physiology and Biochemistry, The Royal Veterinary and Agricultural University, Grønnegaardsvej 7, DK-1870 Frederiksberg C, Denmark |
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Abstract: | 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. |
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Keywords: | Triton X-100 Detergent GABAA receptor Desensitization Xenopus oocyte Voltage-clamp |
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