We propose to explore the physiological mechanisms which shape the discrete responses of photoreceptors to single photons of light. Now that the underlying biochemical similarities among families of signal transduction cascades including those of both vertebrate and invertebrate vision are firmly established, we propose to determine how rhodopsin, GTP-binding proteins and calcium ions control the changes in permeability of thousands of ion channels which give rise to discrete single photon responses. The goals of this proposal are: 1) to determine whether GTP analogs allow a single photoactivated rhodopsin molecule to produce more than one discrete wave in vertebrate rod photoreceptors as they do in Limulus, 2) to determine whether structural changes in rhodopsin chromophores alter the latency or shape of the responses to single photons in Limulus photoreceptors and vertebrate rods and 3) to measure the time course of calcium elevation associated with individual responses to single photons in Limulus. Preliminary work with GTP analogs in the ventral photoreceptors of Limulus have demonstrated the feasibility of this general physiological approach. The first goal is an extension of this work to vertebrate phototransduction. The second goal is also a logical extension of preliminary work in Limulus and takes advantage of a unique opportunity for collaboration that exists at the Medical University of South Carolina. The third goal is a point of departure for a new exploration of the complex role of calcium in phototransduction. A detailed understanding of the physiological mechanisms of receptor-mediated signal transduction cascades should have multiple long range applications in the analysis and treatment of eye disease.
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