Positive allosteric modulation by ultraviolet irradiation on GABA_A, but not GABA_C, receptors expressed in Xenopus oocytes

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. 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 GABA_A receptors varied with receptor subunit composition. UV irradiation decreased the EC₅₀ of the α1β2, α1β2γ2 and β2γ2 GABA_A receptors, but exhibited no significant effect on the ρ1 GABA_C receptor. 6. 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. 7. The effect of UV irradiation on GABA_A receptors did not overlap the effect of the GABA receptor-allosteric modulator, diazepam. 8. 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 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.