Objective To investigate functional homooligomeric GABAρ1 receptors expressed in Xenopus oocytes and the modulation of divalent cations. Methods GABAρ1 cDNA from human retina was transcribed in vitro to obtain sense ρ1 mRNA, which was microinjected into Xenopus oocytes. Two-electrodes voltage clamp technique was performed to record GABA-induced currents. Results Expressed receptors were found to have similar properties to GABA C receptors characterized in the retina. Cl-currents induced by GABA were blocked by picrotoxin instead of bicuculline. GABA-induced currents reversed at -19±2.5 mV, and EC 50 was 3.3 μmol/L. Zn ++ modulated GABA-induced currents with an IC 50=9.6 μ mol/L. Ni ++, Cu ++ and Cd ++ inhibited GABA ρ1 obviously, too. Their rank order of potency was Zn ++>Ni ++>Cu ++>Cd ++. Conclusion Zinc(10 μmol/L) inhibited GABA-induced currents in a competitive manner, and its action was sensitive to extracellular pH. Site-directed mutagenesis revealed that substitution of a single histidine residue (H44 and H48) failed to affect zinc sensitivity.
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