Enhancement of NMDA receptor-mediated currents by light in rat neurones invitro

1. N-Methyl-D-aspartate (NMDA) receptor function can be modified by the act ion of several endogenous and exogenous modulatory processes. In the presen t study, we report that brief pulses of light potentiate NMDA, but not non- NMDA glutamatergic receptor-mediated whole-cell and single channel currents in rat cortical neurones in vitro. In addition, light also potentiated NMD A receptor-mediated whole-cell responses in isolated rat retinal neurones. 2. Potentiation of NMDA whole-cell currents in cortical neurones was readil y observed during and following a brief (< 2 s) exposure of neurones to wav elengths of less than 324 nm of relatively bright light (0.09 mu W mu m(-2) ). In addition, prolonged exposures (> 30 s) to visible wavelengths (> 380 nm) or to attenuated light (1-3% transmittance of non-attenuated light) wer e also sufficient to enhance NMDA receptor-mediated responses. 3. The light-induced potentiation of NMDA receptor-mediated currents persis ted for several minutes, slowly reversing to control levels with a time con stant of approximately 5 min. a subsequent exposure to light could potentia te NMDA receptor-mediated currents for a second time. 4. Light did not alter the apparent affinity of the NMDA receptor for the c o-agonists NMDA and glycine. Additionally, potentiation of the NMDA-induced currents was not mediated by a change in the PH sensitivity of the recepto r. In excised outside-out membrane patches, the effects of light on NMDA-ac tivated unitary currents were manifested as a twofold increase in channel o pen frequency without alterations in single channel amplitude or open time. 5. Our results suggest the presence of a light-sensitive moiety within the NMDA receptor, or in a closely associated structure, which affects channel properties. This previously unrecognized form of NMDA receptor modulation m ay provide a tool for understanding the conformational changes associated w ith its gating. In addition, it is possible that light may affect NMDA rece ptor-mediated function or dysfunction in the retina.