CHLORIDE REGULATION OF PHOTORECEPTOR NEUROTRANSMISSION

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Small reductions in extracellular chloride suppress light-evoked currents in second-order retinal neurons. Thus, physiological regulation of chloride in and around photoreceptors may act in concert with photoreceptor membrane voltage to control transmitter release at this critical first synapse in vision. Regulation of photoreceptor neurotransmission by chloride could affect vision in many ways. For example, changes in chloride levels during sustained illumination might play a role in post-receptoral adaption; chloride fluxes during illumination of the cone receptive field surround could adjust the strength of surround antagonism; and activity-dependent changes in chloride should alter the balance between ON and OFF light responses (which could account for the enhanced sensitivity of ON retinal ganglion cells to ischemia). To assess possible functions of chloride regulation, it is essential to understand the mechanism(s) responsible for the suppression of transmitter release from photoreceptors induced by reductions in extracellular chloride. Besides suppressing light-evoked currents in horizontal and bipolar cells, reducing chloride suppresses the dihydropyridine-sensitive calcium current in photoreceptors. Suppression of this current by dihydropyridine antagonists reduces light responses in second-order retinal neurons. Therefore, it is hypothesized that the suppression of light-evoked currents in second order retinal neurons may arise as a consequence of the suppression of photoreceptor calcium currents induced by reductions in chloride. The two major aims of this proposal are to test this hypothesis further and to analyze the mechanism(s) by which chloride may influence calcium channel function. Whole cell and single channel patch clamp recordings will be used to study the chloride sensitivity of photoreceptor calcium currents, as well as currents evoked by light and spontaneous quantal release in horizontal and bipolar cells of the amphibian retina. These experiments should provide an understanding of the photoreceptor mechanisms responsible for chloride regulation and provide a sound basis for future studies into possible functions of this newly identified regulatory mechanism.