A novel γ-aminobutyric acid receptor subunit (ρ₂) cloned from human retina forms bicuculline-insensitive homooligomeric receptors in Xenopus oocytes

The ρ₂ 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 ρ₁ subunit that forms homooligomeric bicuculline-, barbiturate-, and benzodiazepine-insensitive GABA receptors. The ρ₂ subunit also forms homooligomeric GABA-activated chloride channels when expressed in Xenopus oocytes. The amplitudes of the whole-cell currents of ρ₂ receptors are always smaller than those of ρ₁ receptors, but the affinity and cooperativity of GABA are very similar. Like the ρ₁ subunit, the currents generated by ρ₂ are insensitive to GABA(A) receptor modulators including bicuculline, hexobarbital, and diazepam and can be reversibly inhibited by ZnCl₂. Homooligomeric ρ₂ and ρ₁ receptors are less sensitive to muscimol and picrotoxin, and desensitize slower than GABA(A) receptors. These data demonstrate that homooligomeric receptors formed by ρ₂ and ρ₁ subunits have a number of electrophysiologic and pharmacologic characteristics that differ from receptors formed by GABA(A) receptor subunits. The distinctive properties of ρ 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.