Positive allosteric modulation by ultraviolet irradiation on GABA(A), but not GABA(C), receptors expressed in Xenopus oocytes

1. Recombinant rat GABA(A) (alpha1 beta2, alpha1 beta2 gamma2, beta2 gamma2 ) and human GABA(C) (rho1) receptors were expressed in Xenopus oocytes to e xamine the effect of ultraviolet (UV) light on receptor function, 2. GABA-induced currents in individual oocytes expressing GABA receptors we re tested by two-electrode voltage clamp before, and immediately after, 312 nm UV irradiation. 3. UV irradiation significantly potentiated 10 mum GABA-induced currents in alpha1 beta2 gamma2 GABA receptors. The modulation was irradiation dose de pendent, 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 s till significantly elevated (2.7 +/- 0.3-fold) compared to the control leve l. 5. The effect of UV irradiation on GABA(A) receptors varied with receptor s ubunit composition. UV irradiation decreased the EC50 of the alpha1 beta2, alpha1 beta2 gamma2 and beta2 gamma2 GABA(A) receptors, but exhibited no si gnificant effect on the rho1 GABA(C) receptor. 6. UV irradiation also significantly increased the maximum current 2-fold i n alpha1 beta2 GABA(A) receptors with little effect on the maximum of alpha 1 beta2 gamma2 (1.1-fold) or beta2 gamma2 (1.1-fold) GABA(A) receptors. 7. The effect of UV irradiation on GABA(A) receptors did not overlap the ef fect 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 fre e-radical scavengers: 40 mM D-mannitol, 40 mm imidazole or 40 mm sodium azi de. 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 recepto rs are discussed.