A novel gamma-aminobutyric acid receptor subunit (rho 2) cloned from human retina forms bicuculline-insensitive homooligomeric receptors in Xenopus oocytes.
The rho 2 subunit, a novel GABA receptor subunit, has been cloned from a human retinal complementary DNA library. This subunit shares 74% amino acid sequence identity with the rho 1 subunit that forms homooligomeric bicuculline-, barbiturate-, and benzodiazepine-insensitive GABA receptors. The rho 2 subunit also forms homooligomeric GABA-activated chloride channels when expressed in Xenopus oocytes. The amplitudes of the whole-cell currents of rho 2 receptors are always smaller than those of rho 1 receptors, but the affinity and cooperativity of GABA are very similar. Like the rho 1 subunit, the currents generated by rho 2 are insensitive to GABAA receptor modulators including bicuculline, hexobarbital, and diazepam and can be reversibly inhibited by ZnCl2. Homooligomeric rho 2 and rho 1 receptors are less sensitive to muscimol and picrotoxin, and desensitize slower than GABAA receptors. These data demonstrate that homooligomeric receptors formed by rho 2 and rho 1 subunits have a number of electrophysiologic and pharmacologic characteristics that differ from receptors formed by GABAA receptor subunits. The distinctive properties of rho receptors are very similar to those of bicuculline-insensitive GABA-gated chloride channels identified in retina, suggesting a molecular basis for this form of GABA receptor in visual pathways.
Department of Pediatrics, Johns Hopkins University, School of Medicine, Baltimore, Maryland 21205.
T L
TL
Wang
W B
WB
Guggino
G R
GR
Cutting
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology*; D055598:Chemical Phenomena; D002621:Chemistry; D018118:Chloride Channels / Q000378:metabolism / Q000502:physiology; D003001:Cloning, Molecular; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005260:Female; D006801:Humans; D009118:Muscimol / Q000494:pharmacology; D009865:Oocytes / Q000378:metabolism*; D010852:Picrotoxin / Q000494:pharmacology; D018079:Receptors, GABA / Q000145:classification / Q000187:drug effects* / Q000235:genetics*; D012160:Retina / Q000378:metabolism*; D014981:Xenopus / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D001640:Bicuculline; D018118:Chloride Channels; D009118:Muscimol; D010852:Picrotoxin; D018079:Receptors, GABA; D005680:gamma-Aminobutyric Acid