Triton X-100 inhibits agonist-induced currents and suppresses benzodiazepine modulation of GABA(A) receptors in Xenopus oocytes
Research output: Contribution to journal › Journal article › Research › peer-review
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.
Original language | English |
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Journal | B B A - Biomembranes |
Volume | 1788 |
Issue number | 5 |
Pages (from-to) | 1073-80 |
Number of pages | 7 |
ISSN | 0005-2736 |
DOIs | |
Publication status | Published - 2009 |
Bibliographical note
Keywords: Animals; Biophysical Phenomena; Electrophysiological Phenomena; Female; Flunitrazepam; GABA Modulators; Humans; Lipid Bilayers; Octoxynol; Oocytes; Picrotoxin; Receptors, GABA-A; Recombinant Proteins; Surface-Active Agents; Xenopus laevis
ID: 12703837