title: Reversible modulation of GABA(A) receptor-mediated currents by light is dependent on the redox state of the receptor.
abstract: Light has recently been shown to be a physical modulator of GABAA receptor activity. Here, we further characterize the effects of light on a native cortical and retinal population of GABAA receptors, and identify a possible mechanism for light induced potentiation using recombinant receptors. GABA-induced currents in cortical neurons were observed to be rapidly and reversibly potentiated following exposure to a brief flash of light (0.5-2 s; > 280 nm) directed via an optical fibre (50 micro m i.d.). GABAA receptor-mediated responses in retinal ganglion cells were also enhanced by light, while glycine-induced currents in these cells were unaffected by the same stimulus. We also determined that physiological levels of light, that is, those that would normally reach the retina, also enhanced GABA-induced currents. Finally, we observed that chemical reduction of recombinant alpha1beta2 and alpha1beta2gamma2S GABAA receptors by dithiothreitol substantially attenuated the effects of light. These results suggest that GABAA receptors can be reversibly modified by a brief pulse of light via an allosteric mechanism that is intimately linked to redox modulation.
authors.affiliation: Department of Neurobiology, University of Pittsburgh School of Medicine Pittsburgh, PA 15261, USA.
authors.forename: Daniel N
authors.initials: DN
authors.lastname: Leszkiewicz
authors.forename: Elias
authors.initials: E
authors.lastname: Aizenman
mesh_terms: D000494:Allosteric Regulation; D000818:Animals; D016466:CHO Cells; D002540:Cerebral Cortex / Q000166:cytology; D006224:Cricetinae; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects*; D008027:Light; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000166:cytology; D010084:Oxidation-Reduction; D051381:Rats; D011963:Receptors, GABA-A / Q000737:chemistry* / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: D018690:Excitatory Amino Acid Agonists; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate