| Ligand-gated ion channels are responsible for fast synaptic transmission in the central nervous system. These channels are essential for initiating changes in synaptic activity and intracellular signaling cascades. Mutation and misexpression of these neurotransmitter receptors are responsible for a number of disease states, and overactivation of a subset of these receptors may lead to cell death. Receptor-mediated responses are affected by a number of different physiological factors. The work presented here demonstrates that light is a novel modulator of ion channel function. The goals of this dissertation were to describe the characteristics of the light mediated enhancement of NMDA and GABAA induced currents, and identify the structural moiety responsible for the effects of light on ion channel function. Brief pulses of light reversibly potentiated currents activated by both GABA and NMDA receptors in cortical and retinal neurons. Additionally, I have demonstrated that physiological intensities and wavelengths of light enhance channel currents. While the precise light sensitive domain has remained elusive, chemical reduction, inactivation, and mutation of a redox site attenuates the light modulation of receptor-mediated responses. Collectively, these results suggest that light may play an important physiological role by modulating ion channel function via an allosteric structural change coupled to the redox site. |
