We propose to investigate the molecular mechanism of visual transduction in retinal rods and the flow of signals to retinal ganglion cells. Patch clamp methods will he used to ask the following questions about the cGMP-activated cation channel that generates the rod response to light: 1) How does activation of the channel by CGMP regulate the flow of ions through it? Where is the ligand-controlled gate located relative to the cation binding site? 2) Does covalent modification of channels regulate the channel response to cGMP? What signals control modification, and what is the molecular mechanism? 3) What is the radial distribution of cGMP-activated channels on the rod outer segment? 4) By what mechanism do divalent cations such as Ni++ and Zn++ potentiate the channel's response to cGMP? Does potentiation by divalent cations regulate channel sensitivity under physiological conditions? 5) At the single channel level, how do the open state conductances and gating kinetics of the channel depend on cGMP concentration and membrane potential? Using a new multielectrode recording method we will study correlations in the spontaneous and light-evoked spike discharges of retinal ganglion cells, asking: 1) In darkness and dim light, how do the correlations between impulses in nearby retinal ganglion cells depend on cell type, cell separation and time? 2) What is the spatial distribution of ganglion cells of different functional types? 3) What is the response of the ganglion cell population to photoisomerization of a single rhodopsin molecule? Answers to these questions may help to provide a clearer understanding of visual disturbances in disease.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37EY001543-21
Application #
2158156
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1977-09-01
Project End
1995-08-31
Budget Start
1994-09-01
Budget End
1995-08-31
Support Year
21
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Stanford University
Department
Biology
Type
Schools of Medicine
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305
Sampath, Alapakkam P; Baylor, Denis A (2002) Molecular mechanism of spontaneous pigment activation in retinal cones. Biophys J 83:184-93
Burns, M E; Baylor, D A (2001) Activation, deactivation, and adaptation in vertebrate photoreceptor cells. Annu Rev Neurosci 24:779-805
Middendorf, T R; Aldrich, R W; Baylor, D A (2000) Modification of cyclic nucleotide-gated ion channels by ultraviolet light. J Gen Physiol 116:227-52
Middendorf, T R; Aldrich, R W (2000) Effects of ultraviolet modification on the gating energetics of cyclic nucleotide-gated channels. J Gen Physiol 116:253-82
Rieke, F; Baylor, D A (2000) Origin and functional impact of dark noise in retinal cones. Neuron 26:181-6
Makino, C L; Groesbeek, M; Lugtenburg, J et al. (1999) Spectral tuning in salamander visual pigments studied with dihydroretinal chromophores. Biophys J 77:1024-35
Rieke, F; Baylor, D A (1998) Origin of reproducibility in the responses of retinal rods to single photons. Biophys J 75:1836-57
Erickson, M A; Lagnado, L; Zozulya, S et al. (1998) The effect of recombinant recoverin on the photoresponse of truncated rod photoreceptors. Proc Natl Acad Sci U S A 95:6474-9
Rieke, F; Baylor, D A (1996) Molecular origin of continuous dark noise in rod photoreceptors. Biophys J 71:2553-72
Baylor, D (1996) How photons start vision. Proc Natl Acad Sci U S A 93:560-5

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