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Positive allosteric modulation by ultraviolet irradiation on GABA A , but not GABA C , receptors expressed in Xenopus oocytes
Author(s) -
Chang Yongchang,
Xie Yi,
Weiss David S.
Publication year - 2001
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.2001.0471c.xd
Subject(s) - gabaa receptor , receptor , allosteric regulation , chemistry , xenopus , long term potentiation , gabaa rho receptor , biophysics , gamma aminobutyric acid , allosteric modulator , irradiation , voltage clamp , endocrinology , medicine , biology , biochemistry , membrane potential , physics , nuclear physics , gene
1 Recombinant rat GABA A (α1β2, α1β2γ2, β2γ2) and human GABA C (ρ1) receptors were expressed in Xenopus oocytes to examine the effect of ultraviolet (UV) light on receptor function. 2 GABA‐induced currents in individual oocytes expressing GABA receptors were tested by two‐electrode voltage clamp before, and immediately after, 312 nm UV irradiation. 2 UV irradiation significantly potentiated 10 μ m GABA‐induced currents in α1β2γ2 GABA receptors. The modulation was irradiation dose dependent, with a maximum potentiation of more than 3‐fold. 3 The potentiation was partially reversible and decayed exponentially with a time constant of 8.2 ± 1.2 min toward a steady‐state level which was still significantly elevated (2.7 ± 0.3‐fold) compared to the control level. 4 The effect of UV irradiation on GABA A receptors varied with receptor subunit composition. UV irradiation decreased the EC 50 of the α1β2, α1β2γ2 and β2γ2 GABA A receptors, but exhibited no significant effect on the ρ1 GABA C receptor. 5 UV irradiation also significantly increased the maximum current 2‐fold in α1β2 GABA A receptors with little effect on the maximum of α1β2γ2 (1.1‐fold) or β2γ2 (1.1‐fold) GABA A receptors. 6 The effect of UV irradiation on GABA A receptors did not overlap the effect of the GABA receptor‐ allosteric modulator, diazepam. 7 The UV effect on GABA A receptors was not prevented by the treatment of the oocytes before and during UV irradiation with one of the following free‐radical scavengers: 40 m m d ‐mannitol, 40 m m imidazole or 40 m m sodium azide. In addition, the effect was not mimicked by the free‐radical generator, H 2 O 2 . 8 Potential significance and mechanism(s) of the UV effect on GABA receptors are discussed.