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.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
1R01EY007543-01
Application #
3264504
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1988-03-01
Project End
1993-02-28
Budget Start
1988-03-01
Budget End
1989-02-28
Support Year
1
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Medical University of South Carolina
Department
Type
School of Medicine & Dentistry
DUNS #
183710748
City
Charleston
State
SC
Country
United States
Zip Code
29425
Corson, D Wesley; Pepperberg, David R (2003) Conditioning light differentially desensitizes rod phototransduction mediated by native and 9-demethyl analog visual pigment. Vis Neurosci 20:29-36
Ma, J; Znoiko, S; Othersen, K L et al. (2001) A visual pigment expressed in both rod and cone photoreceptors. Neuron 32:451-61
Corson, D W; Kefalov, V J; Cornwall, M C et al. (2000) Effect of 11-cis 13-demethylretinal on phototransduction in bleach-adapted rod and cone photoreceptors. J Gen Physiol 116:283-97
Li, Z; Zhuang, J; Corson, D W (1999) Delivery of 9-Cis retinal to photoreceptors from bovine serum albumin. Photochem Photobiol 69:500-4
Martinez, L M; Crouch, R K; Corson, D W (1997) Application of a submicroliter spectrophotometer in visual pigment studies. Mol Vis 3:4
Chen, N; Ma, J X; Corson, D W et al. (1996) Molecular cloning of a rhodopsin gene from salamander rods. Invest Ophthalmol Vis Sci 37:1907-13
Corson, D W; Crouch, R K (1996) Physiological activity of retinoids in natural and artificial visual pigments. Photochem Photobiol 63:595-600
Corson, D W; Cornwall, M C; Pepperberg, D R (1994) Evidence for the prolonged photoactivated lifetime of an analogue visual pigment containing 11-cis 9-desmethylretinal. Vis Neurosci 11:91-8
Corson, D W; Cornwall, M C; MacNichol, E F et al. (1994) Relief of opsin desensitization and prolonged excitation of rod photoreceptors by 9-desmethylretinal. Proc Natl Acad Sci U S A 91:6958-62
Jin, J; Crouch, R K; Corson, D W et al. (1993) Noncovalent occupancy of the retinal-binding pocket of opsin diminishes bleaching adaptation of retinal cones. Neuron 11:513-22

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