Cone photoreceptors function under daylight conditions and are essential for color perception and vision with high temporal and spatial resolution. A remarkable feature of cones is their ability to remain functional in bright light which requires powerful adaptation mechanisms of their phototransduction cascade. In rods, light adaptation is mediated by calcium and the mechanisms by which reduction in calcium upon photo-activation modulates phototransduction are well understood. While photo-activation also triggers a decline in calcium in cones, the molecular mechanisms by which this exerts negative feedback on cone phototransduction are not known. The experiments described here will employ physiological studies from available genetically modified mice to investigate the mechanisms of modulation of the cone phototransduction cascade by calcium. Specifically, we will test the hypothesis that regulation of visual pigment phosphorylation by rhodopsin kinase via recoverin is a component of the calcium feedback in mouse cones and modulates their phototransduction in darkness and during light adaptation. We will also test the hypothesis that regulation of cGMP synthesis by guanylyl cyclase via Guanylyl Cyclase Activating Proteins (GCAPs) is a major component of the calcium feedback in mouse cones and modulates their phototransduction in darkness and during light adaptation. Together, these experiments will help us determine the mechanisms that allow cones to adapt to a very wide range of light intensities and remain functional throughout the day, even in bright light.

Public Health Relevance

The experiments outlined in this proposal seek to establish the mechanisms that enable mammalian cones to function in bright light, an essential property for the photoreceptors that mediate daytime vision. These studies will help us understand the role of calcium in regulating mammalian cone function under normal and pathological conditions.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21EY019543-01
Application #
7638095
Study Section
Special Emphasis Panel (ZRG1-CB-G (90))
Program Officer
Mariani, Andrew P
Project Start
2009-09-01
Project End
2011-08-31
Budget Start
2009-09-01
Budget End
2010-08-31
Support Year
1
Fiscal Year
2009
Total Cost
$114,625
Indirect Cost
Name
Washington University
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Sakurai, Keisuke; Vinberg, Frans; Wang, Tian et al. (2016) The Na(+)/Ca(2+), K(+) exchanger 2 modulates mammalian cone phototransduction. Sci Rep 6:32521
Sakurai, Keisuke; Chen, Jeannie; Khani, Shahrokh C et al. (2015) Regulation of mammalian cone phototransduction by recoverin and rhodopsin kinase. J Biol Chem 290:9239-50
Kolesnikov, Alexander V; Kefalov, Vladimir J (2012) Transretinal ERG recordings from mouse retina: rod and cone photoresponses. J Vis Exp :
Sakurai, Keisuke; Chen, Jeannie; Kefalov, Vladimir J (2011) Role of guanylyl cyclase modulation in mouse cone phototransduction. J Neurosci 31:7991-8000
Kolesnikov, Alexander V; Rikimaru, Loryn; Hennig, Anne K et al. (2011) G-protein betagamma-complex is crucial for efficient signal amplification in vision. J Neurosci 31:8067-77
Wang, Jin-Shan; Kefalov, Vladimir J (2011) The cone-specific visual cycle. Prog Retin Eye Res 30:115-28
Kefalov, Vladimir J; Cornwall, M Carter; Fain, Gordon L (2010) Physiological studies of the interaction between opsin and chromophore in rod and cone visual pigments. Methods Mol Biol 652:95-114