The ρ1 GABA receptor cloned from rat retina is down-modulated by protons

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Abstract
We have cloned and sequenced the full-length cDNA of the rat GABA (γ-aminobutyric acid) ρ1 receptor subunit. The deduced amino acid sequence (474 amino acids) of the rat ρ1 receptor is 95% homologous to the previously cloned human ρ1 receptor. The ρ1 cDNA includes a 5' 129 bp and a 3' 2.6 kb untranslated region, which contains a sequence homologous to the human medium reiteration frequency repetitive sequence, MER18. The rat ρ1 receptor shows 45–50% similarity to the GABAA receptor β subunits. This similarity is among the highest between all GABAA receptor subunit classes, giving no support at the molecular level to the classification of the p subunits to a novel GABAC receptor class. The rat ρ1 cDNA formed functional GABA receptors insensitive to bicuculline, but sensitive to blockade by picrotoxin, when transiently expressed in the human embryonic kidney cell line HER 293. We studied the sensitivity of the ρ1-mediated GABA current to variations in extracellular pH (pH0), and found that these receptors are strongly down-modulated by H+ ions. A decrease in pH0 from 7.4 to 6.4 decreased the GABA current by 51 ± 8%, whereas an increase in pH0 from 7.4 to 8.4 increased the current by 77 ± 8%. In view of the up-regulatory effect of protons on the GABA current observed in a number of preparations, the ρ1 receptors may contain a novel down-regulatory binding site for protons characteristic to these receptors.

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