Positive allosteric modulation by ultraviolet irradiation on GABAA, but not GABAC, receptors expressed in Xenopus oocytes

Yongchang Chang, Yi Xie, David S. Weiss

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

1. Recombinant rat GABAA (α1β2, α1β2γ2, β2γ2) and human GABAC (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. 3. UV irradiation significantly potentiated 10 μM GABA-induced currents in α1β2γ2 GABA receptors. The modulation was irradiation dose dependent, with a maximum potentiation of more than 3-fold. 4. 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. 5. The effect of UV irradiation on GABAA receptors varied with receptor subunit composition. UV irradiation decreased the EC50 of the α1β2, α1β2γ2 and β2γ2 GABAA receptors, but exhibited no significant effect on the ρ1 GABAC receptor. 6. UV irradiation also significantly increased the maximum current 2-fold in α1β2 GABAA receptors with little effect on the maximum of α1β2γ2 (1.1-fold) or β2γ2 (1.1-fold) GABAA receptors. 7. The effect of UV irradiation on GABAA receptors did not overlap the effect of the GABA receptor-allosteric modulator, diazepam. 8. The UV effect on GABAA receptors was not prevented by the treatment of the oocytes before and during UV irradiation with one of the following free-radical scavengers: 40 mM D-mannitol, 40 mM imidazole or 40 mM sodium azide. In addition, the effect was not mimicked by the free-radical generator, H2O2. 9. Potential significance and mechanism(s) of the UV effect on GABA receptors are discussed.

Original languageEnglish (US)
Pages (from-to)471-478
Number of pages8
JournalJournal of Physiology
Volume536
Issue number2
DOIs
StatePublished - Oct 15 2001
Externally publishedYes

ASJC Scopus subject areas

  • Physiology

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