GABA action in retina is mediated by GABA-A, GABA-B and GABA-C receptors. Although GABA-A and GABA-C receptors share certain features, the GABA-C receptors have a more prolonged and sensitive response to GABA and display a pharmacological profile of agonists and antagonists that is distinct from the other GABA receptors. In addition, GABA-C receptors appear to be retina-specific, and are expressed by bipolars and horizontal cells. The molecular composition of GABA-C receptors is controversial. Previously, the applicant's laboratory has cloned two novel GABA receptor subunits, rho1 and rho2, from bovine retina and found them to have structural similarity to the GABA-A receptor. Interestingly, expression of rho1 and rho2 in Xenopus oocytes results in homo-oligomeric receptors with electrophysiological properties similar to GABA-C receptors. Since rho subunits are expressed in retinal cells that exhibit GABA-C properties, GABA-C could be made up of rho subunits. Bipolars that express GABA-C also contain GABA-A and glycine receptors. Therefore, GABA-C receptors could be a mixture of subunits from different classes of receptors. The goal of this proposal is to determine the role the rho subunits play in the formation of mammalian retinal GABA-C receptors. The applicant will use a molecular approach to examine which subunit combinations create receptors with properties matching those of GABA-C receptors identified in vivo. This information will guide a search for amino acid sequences that specify assembly of subunits into GABA-C receptors. Finally, the applicant will test for specific subunit combinations in vivo by immunoprecipitation of bovine retina.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY009531-07
Application #
2838314
Study Section
Visual Sciences C Study Section (VISC)
Project Start
1992-12-01
Project End
2000-11-30
Budget Start
1998-12-01
Budget End
2000-11-30
Support Year
7
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Pediatrics
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
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Enz, R; Ross, B J; Cutting, G R (1999) Expression of the voltage-gated chloride channel ClC-2 in rod bipolar cells of the rat retina. J Neurosci 19:9841-7
Enz, R; Cutting, G R (1999) Identification of 70 amino acids important for GABA(C) receptor rho1 subunit assembly. Brain Res 846:177-85
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