Molecular and pharmacological properties of GABA-rho subunits from white perch retina.
Five gamma-aminobutyric acid (GABA)-rho subunits were cloned from a white perch retinal cDNA library and expressed in Xenopus oocytes. The deduced amino acid sequences indicated that all are highly homologous to the GABA-rho subunits cloned from mammalian retinas; two clones (perch-rho 1A and perch-rho 1B) were in the rho 1 family, two (perch-rho 2A and perch-rho 2B) were in the rho 2 family, and one clone has been tentatively identified as a perch-rho 3 subunit. When expressed in Xenopus oocytes, all but one of the subunits (rho 3) formed functional homooligomeric receptors. However, the receptors expressed by each of the GABA-rho subunits displayed unique response properties that distinguished one from the other. For example, receptors formed by perch-rho 1B subunits were more sensitive to GABA than the receptors formed by other GABA-rho subunits, the dose-response curves for the various receptors revealed different Hill coefficients, and there were differences in the kinetics of the GABA-induced currents. In addition, the GABA-mediated current-voltage curve for rho 2 receptors was approximately linear, whereas the responses from rho 1 receptors showed outward rectification. A further division in the properties of the GABA-rho subunits was revealed in their responses to imidazole-4-acetic acid (I4AA); the drug behaved as an antagonist on A-type rho receptors and a partial agonist on the B-type rho receptors. These results suggest that there is a large diversity of GABAC receptors in the vertebrate retina, probably formed by homooligomeric and heterooligomeric combinations of GABA rho subunits, that exhibit different functional properties.
Qian
H
H
Lions of Illinois Eye Research Institute, Department of Ophthalmology and Visual Sciences, University of Illinois College of Medicine 60612, USA.
Dowling
J E
JE
Ripps
H
H
D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology; D015723:Gene Library; D007700:Kinetics; D008969:Molecular Sequence Data; D009865:Oocytes / Q000378:metabolism; D010471:Perches / Q000378:metabolism*; D010852:Picrotoxin / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000145:classification; D012160:Retina / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid; D014981:Xenopus; D015032:Zinc / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000737:chemistry / Q000494:pharmacology*
D018756:GABA Antagonists; D010852:Picrotoxin; D011963:Receptors, GABA-A; D015032:Zinc; D005680:gamma-Aminobutyric Acid