Triton X-100 inhibits agonist-induced currents and suppresses benzodiazepine modulation of GABA(A) receptors in Xenopus oocytes.
Changes in lipid bilayer elastic properties have been proposed to underlie the modulation of voltage-gated Na(+) and L-type Ca(2+) channels and GABA(A) 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 GABA(A) receptors expressed in Xenopus laevis oocytes was examined. Triton-X 100 inhibited GABA(A) alpha(1)beta(3)gamma(2S) receptor currents in a noncompetitive, time- and voltage-dependent manner and increased the apparent rate and extent of desensitization at 10 muM, which is 30 fold below the critical micelle concentration. In addition, Triton X-100 induced picrotoxin-sensitive GABA(A) receptor currents and suppressed allosteric modulation by flunitrazepam at alpha(1)beta(3)gamma(2S) receptors. All effects were independent of the presence of a gamma(2S) subunit in the GABA(A) receptor complex. The present study suggests that Triton X-100 may stabilize open and desensitized states of the GABA(A) receptor through changes in lipid bilayer elasticity.
Institute of Cellular and Molecular Medicine, Panum 12.6, University of Copenhagen, Blegdamsvej 3C, DK-2200, Copenhagen N, Denmark. rikkes@sund.ku.dk
Rikke
R
Søgaard
Bjarke
B
Ebert
Dan
D
Klaerke
Thomas
T
Werge
D000818:Animals; D055592:Biophysical Phenomena; D055724:Electrophysiological Phenomena; D005260:Female; D005445:Flunitrazepam / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology*; D058785:GABA-A Receptor Agonists; D006801:Humans; D066298:In Vitro Techniques; D008051:Lipid Bilayers; D017830:Octoxynol / Q000494:pharmacology*; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D010852:Picrotoxin / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000819:agonists / Q000187:drug effects / Q000378:metabolism; D013501:Surface-Active Agents / Q000494:pharmacology; D014982:Xenopus laevis
D005445:Flunitrazepam; D018757:GABA Modulators; D058785:GABA-A Receptor Agonists; D008051:Lipid Bilayers; D017830:Octoxynol; D010852:Picrotoxin; D011963:Receptors, GABA-A; D011994:Recombinant Proteins; D013501:Surface-Active Agents