This proposal consists of two parts. In the first, we propose to study the physiology and pharmacology of synaptic receptors of goldfish ganglion cells, both for enzymatically dissociated cells in culture and for cells in slices of intact retina. Recordings from ganglion cells will be made with patch-clamp techniques in both the whole-cell and isolated patch modes. We plan (1), a characterization of excitatory amino acid receptors on isolated ganglion cells; (2), further study of the effects of inhibitory amino acids, including a study of the nature of GABA desensitization, an investigation of the mechanism of strychnine block for GABA and glycine, and an explanation of the noise spectrum for glycine whole-cell currents in terms of single-channel responses; (3), a survey of the effects of peptides and other putative neurotransmitters on dissociated ganglion cells; and (4), the development of a system for making recordings from ganglion cells in slices of goldfish retina. In the second part of this proposal, we propose to use microelectrode recording, external perfusion, and microspectrophotometry to elucidate the mechanism of dark adaptation in vertebrate rods and cones. These experiments are designed to test the """"""""equivalent background hypothesis"""""""" of dark adaptation at the level of single photoreceptors. We also plan to investigate a possible role for intracellular calcium concentration in controlling sensitivity during recovery after pigment bleaching.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
4R37EY001844-19
Application #
2158239
Study Section
Special Emphasis Panel (NSS)
Project Start
1984-07-01
Project End
2000-01-31
Budget Start
1995-02-01
Budget End
1996-01-31
Support Year
19
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Physiology
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Wang, Tian; Reingruber, Jürgen; Woodruff, Michael L et al. (2018) The PDE6 mutation in the rd10 retinal degeneration mouse model causes protein mislocalization and instability and promotes cell death through increased ion influx. J Biol Chem 293:15332-15346
Chen, Ching-Kang; Woodruff, Michael L; Fain, Gordon L (2015) Rhodopsin kinase and recoverin modulate phosphodiesterase during mouse photoreceptor light adaptation. J Gen Physiol 145:213-24
Reingruber, Jürgen; Holcman, David; Fain, Gordon L (2015) How rods respond to single photons: Key adaptations of a G-protein cascade that enable vision at the physical limit of perception. Bioessays 37:1243-52
Morshedian, Ala; Fain, Gordon L (2015) Single-photon sensitivity of lamprey rods with cone-like outer segments. Curr Biol 25:484-7
Woodruff, Michael L; Rajala, Ammaji; Fain, Gordon L et al. (2015) Effect of knocking down the insulin receptor on mouse rod responses. Sci Rep 5:7858
Woodruff, Michael L; Rajala, Ammaji; Fain, Gordon L et al. (2014) Modulation of mouse rod photoreceptor responses by Grb14 protein. J Biol Chem 289:358-64
Reingruber, Jürgen; Pahlberg, Johan; Woodruff, Michael L et al. (2013) Detection of single photons by toad and mouse rods. Proc Natl Acad Sci U S A 110:19378-83
Chen, Ching-Kang; Woodruff, Michael L; Chen, Frank S et al. (2012) Modulation of mouse rod response decay by rhodopsin kinase and recoverin. J Neurosci 32:15998-6006
Tsang, Stephen H; Woodruff, Michael L; Lin, Chyuan-Sheng et al. (2012) Effect of the ILE86TER mutation in the ? subunit of cGMP phosphodiesterase (PDE6) on rod photoreceptor signaling. Cell Signal 24:181-8
Nymark, S; Frederiksen, R; Woodruff, M L et al. (2012) Bleaching of mouse rods: microspectrophotometry and suction-electrode recording. J Physiol 590:2353-64

Showing the most recent 10 out of 56 publications