The main goal of the proposed research is to investigate the hypothesis that the receptor potential of the vertebrate rod photoreceptor is mediated by a rise in the cytoplasmic concentration of a diffusible """"""""internal transmitter"""""""" substance. We will test the hypothesis that this internal transmitter is Ca+2 ions by injecting Ca+2-ligand solutions intracellularly with pressure in order to adjust (Ca+2)in while membrane potential, current and conductance are measured. Changes in these variables will be measured while the cell is bathed in normal Ringer's solution and solutions with low (Na+), (Cl-), and (Ca+2) in order to determine the ionic specificity for the conductance changes. For the above measurements both rods in the isolated retina and enzymatically isolated, solitary rods will be used. Furthermore, the effects of intracellular injection of Ca+2-ligand solutions upon the amplitude andkinetics of the light responses of these solitary rods will investigated. The hypothesis that (cyclic GMP)in is the """"""""internal transmitter"""""""" will also be investigated by intracellularly injecting this and related compounds while making the above electrical measurements to determine the ionic specificity for the conductance changes that are produced. A second area of research is to deterine if electrophysiologically observable change occur in the retinas of rats with inherited retinal dystrophy (RCS rats) before photoreceptor death occurs (on about postnatal day 18) in thes mutants. In the posterior retina, histochemical changes have been reported to precede photoreceptor cell death; therefore, we will measure photoreceptor responses that are induced by light falling on the posterior retinas of animals from 8-20 days of age (postnatal) to determine if physiological changes also precede cell death. These studies will yield information about the effect of electrolyte changes upon retinal function and will thus help provide the fundamental basis for understanding vidual defects that occur in conjunction with some metabolic and endocrine disorders. Also, information about the RCS model for human retinitis pigmentosa will be gathered.
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