Permeability and single channel conductance of human homomeric ρ1 GABAC receptors

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Abstract
Homomeric human ρ1 GABAC receptors were expressed in Xenopus oocytes and in human embryonic kidney cells (HEK293) in order to examine their conductance and permeability. Reversal potentials of currents elicited by γ-aminobutyric acid (GABA) were measured in extracellular solutions of various ionic composition to determine relative permeability of homomeric ρ1 receptors. The rank order of anionic permeability was: SCN− > I− > NO3− > Br− > Cl− > formate (For−) > HCO3− > acetate (Ac−) ≈ proprionate (Prop−) ≈ isethionate (Ise−) ≈ F−≈ PO4−. In the oocyte expression system, relative permeabilities to SCN−, I−, NO3−, Br− and HCO3− were higher for ρ1 GABAC receptors than α1β2γ2L GABAA receptors. Expression of ρ1 GABAC receptors in Xenopus oocytes and in HEK293 cells gave similar relative permeabilities for selected anions, suggesting that the expression system does not significantly alter permeation properties. The pore diameter of the homomeric ρ1 GABAC receptor expressed in oocytes was estimated to be 0.61 nm, which is somewhat larger than the 0.56 nm pore diameter estimated for α1β2γ2L GABAA receptors. Homomeric ρ1 GABA receptors expressed in oocytes had a single channel chord conductance of 0.65 ± 0.04 pS (mean ±s.e.m.s) when the internal chloride concentration ([Cl−]i) was 20 mm. With a [Cl−]i of 100 mm, the single channel chord conductance was 1.59 ± 0.24 pS. The mean open time directly measured from 43 GABA-induced channel openings in six patches was 3.2 ± 0.8 s. The mean open time in the presence of 100 μm picrotoxin was 0.07 ± 0.01 s (77 openings from 3 patches). The differences observed in ionic permeabilities, pore size, single channel conductance and mean open time suggest that the ρ1 homomeric receptor may not be the native retinal GABAC receptor reported previously.