Figure 1

Glycine receptors expressed show expression-system dependent agonist pharmacology. (A) Glycine has a reduced potency in L-cells compared to HEK cells. Glycine current responses were plotted versus the log concentration of glycine and normalized to a maximal concentration of glycine (3–10 mM). Data are presented as mean ± SEM; 4 ≤ n ≤ 9 cells for each concentration. Concentration response relationships for GlyRα₂ (□; EC₅₀ = 221 μM) and GlyRα₂β (○; 269 μM) in HEK cells and in L-cells (GlyRα₂, ■, 446 μM; GlyRα₂β, ●; 667 μM) were derived from logistic equation fits to individual cells. (B) β-alanine has both reduced apparent affinity and efficacy for most glycine receptor isoforms transiently expressed in L-cells compared to HEK 293 cells. β-alanine apparent potency in HEK 293 cells was 717 μM for GlyRα₂ (□, n = 6) and 560 μM for GlyRα₂β (○, n = 7). For L-cells, β-alanine potency for GlyRα₂ (■, n = 5–8) was 1.61 mM and 1.79 mM for GlyRα₂β (●, n = 7). Current responses were normalized to a maximal concentration of glycine (10 mM). Note the reduced apparent efficacy of α₂β receptors compared to the α₂ homomeric isoforms. (C) Taurine has both reduced apparent affinity and efficacy to GlyRs transiently expressed in L-cells compared to HEK 293 cells. Taurine concentration-response relationship in HEK 293 for GlyRα₂ (□; 442 μM, n = 5–6) and GlyRα₂β (○; 1.25 mM, n = 3–5). Taurine concentration-response relationship in L-cells yielded GlyRα₂ (■, n = 4) and GlyRα₂β (●, n = 7) potencies estimated at ≥ 3 mM. Current responses were plotted versus the log concentration of taurine and normalized to a maximal concentration of glycine.