Activation of human α1 and α2 homomeric glycine receptors by taurine and GABA

1 Two ligand binding α subunits, α1 and α2, of the human (H) glycine receptor (GlyR) are involved at inhibitory synapses in the adult and neonatal spinal cord, respectively. The ability of homomeric αH1 and αH2 GlyRs to be activated by glycine, taurine and GABA was studied in Xenopus oocytes or in the human embryonic kidney HEK‐293 cell line. 2 In outside‐out patches from HEK cells, glycine, taurine and GABA activated both GlyRs with the same main unitary conductance, i.e. 85 ± 3 pS (n= 6) for αH1, and 95 ± 5 pS (n = 4) for αH2. 3 The sensitivity of both αH1 and αH2 GlyRs to glycine was highly variable. In Xenopus oocytes the EC50 for glycine (EC50gly) was between 25 and 280 μm for αH1 (n= 44) and between 46 and 541 μm for αH2 (n= 52). For both receptors, the highest EC50gly values were found on cells with low maximal glycine responses. 4 The actions of taurine and GABA were dependent on the EC50gly: (i) their EC50 values were linearly correlated to EC50gly, with EC50tau≈ 10 EC50gly and EC50GABA≈ 500‐800 EC50gly; (ii) they could act either as full or weak agonists depending on the EC50gly. 5 The Hill coefficient (nH) of glycine remained stable regardless of the EC50gly whereas nH for taurine decreased with increasing EC50tau. 6 The degree of desensitization, evaluated by fast application of saturating concentrations of agonist on outside‐out patches from Xenopus oocytes, was similar for glycine and taurine on both GlyRs and did not exceed 50 %. 7 Our data concerning the variations of EC50gly and the subsequent behaviour of taurine and GABA could be qualitatively described by the simple del Castillo‐Katz scheme, assuming that the agonist gating constant varies whereas the binding constants are stable. However, the stability of the Hill coefficient for glycine was not explained by this model, suggesting that other mechanisms are involved in the modulation of EC50.