Triton X-100 inhibits agonist-induced currents and suppresses benzodiazepine modulation of GABA(A) receptors in Xenopus oocytes
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Triton X-100 inhibits agonist-induced currents and suppresses benzodiazepine modulation of GABA(A) receptors in Xenopus oocytes. / Søgaard, Rikke; Ebert, Bjarke; Klaerke, Dan; Werge, Thomas; Søgaard, Rikke; Ebert, Bjarke; Klaerke, Dan; Werge, Thomas.
I: B B A - Biomembranes, Bind 1788, Nr. 5, 2009, s. 1073-80.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Triton X-100 inhibits agonist-induced currents and suppresses benzodiazepine modulation of GABA(A) receptors in Xenopus oocytes
AU - Søgaard, Rikke
AU - Ebert, Bjarke
AU - Klaerke, Dan
AU - Werge, Thomas
AU - Søgaard, Rikke
AU - Ebert, Bjarke
AU - Klaerke, Dan
AU - Werge, Thomas
N1 - 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
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
U2 - 10.1016/j.bbamem.2009.02.001
DO - 10.1016/j.bbamem.2009.02.001
M3 - Journal article
C2 - 19366585
VL - 1788
SP - 1073
EP - 1080
JO - B B A - Biomembranes
JF - B B A - Biomembranes
SN - 0005-2736
IS - 5
ER -
ID: 12703837