Positive allosteric modulation by ultraviolet irradiation on GABA(A), but not GABA(C), receptors expressed in Xenopus oocytes.
1. Recombinant rat GABA(A) (alpha1beta2, alpha1beta2gamma2, beta2gamma2) and human GABA(C) (rho1) 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 microM GABA-induced currents in alpha1beta2gamma2 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 alpha1beta2, alpha1beta2gamma2 and beta2gamma2 GABA(A) receptors, but exhibited no significant effect on the rho1 GABA(C) receptor. 6. UV irradiation also significantly increased the maximum current 2-fold in alpha1beta2 GABA(A) receptors with little effect on the maximum of alpha1beta2gamma2 (1.1-fold) or beta2gamma2 (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.
Chang
Y
Y
Department of Neurobiology, University of Alabama at Birmingham, 1719 Sixth Avenue South, CIRC410, Birmingham, AL 35294-0021, USA.
Xie
Y
Y
Weiss
D S
DS
D000494:Allosteric Regulation / Q000528:radiation effects; D000818:Animals; D003975:Diazepam / Q000494:pharmacology; D004307:Dose-Response Relationship, Radiation; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D015870:Gene Expression / Q000502:physiology; D008027:Light; D008564:Membrane Potentials / Q000187:drug effects / Q000528:radiation effects; D009865:Oocytes / Q000502:physiology; D018408:Patch-Clamp Techniques; D018079:Receptors, GABA / Q000737:chemistry / Q000235:genetics; D011963:Receptors, GABA-A / Q000737:chemistry* / Q000235:genetics*; D012160:Retina / Q000528:radiation effects; D014466:Ultraviolet Rays; D014982:Xenopus laevis
D016166:Free Radical Scavengers; D018757:GABA Modulators; C087200:GABA-C receptor; D018079:Receptors, GABA; D011963:Receptors, GABA-A; D003975:Diazepam