The objective of the proposed project is to identify those physiological processes that are postulated to function as intermediate steps in phototransduction. For this purpose, we will use specific Drosophila mutants that conditionally express their mutant receptor-potential phenotypes only under specific experimental conditions (temperature, background light, etc.). Thus, it is possible to control the strength of phenotypic expression in these mutants by systematically manipulating the experimental conditions. While recording the receptor potential either intra- or extracellularly from superfused head preparations, various agents will be applied to the superfusate to alter the degree of phenotypic expression in the mutants or similate the effect of the mutation in wild type. From such studies we hope to elucidate those characteristics of the intermediate steps that are defective in the mutants. By applying more than one experimental manipulation simultaneously, we will examine the effect of interactions among partial blocks in the receptor potential parameters produced by various manipulations. These experiments are intended for elucidation of the sequence of events leading to the generation of the receptor potential. We will also examine the effects of the mutations on the PDA (the prolonged depolarizaing afterpotential). Since the PDA decouples the immeidate effects of pigment photoexcitation from later processes, it is expected to be very useful in the study of phototransduction. The mechanism of hereditary retinal degeneration will be examined in a particular Drosophila mutant in which the degeneration process appears to be closely linked to a defective phototransduction step. Finally, we will formulate a quantitative model for phototransduction incorporating the results of the above studies.
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