γ-Amino butyric acid (GABA)_A–activated Cl^– channels are the targets for a range of clinically used drugs. However, in the absence of well characterised fast Cl^–-sensitive fluorophores, configuring meaningful high throughput, functional assays for these channels remains a challenge. In this study we have explored population patch clamp (PPC) using the IonWorks Quattro planar array electrophysiology platform (Finkel et al, 2006) as a possible approach to this end. HEK293 cells stably co-expressing human GABA_A α1, β3 and γ2 subunits were used as a model system throughout. GABA-evoked currents were recorded 8s post-drug addition, in a PBS external solution (containing 138mM NaCl) and K-gluconate (140mM), MgCl₂ (5mM) based internal, containing 100μM amphotericin (theoretical Cl^– E_rev -66mV). Confounding leak currents were minimised by measuring currents at 0mV (John et al, 2007). GABA (30μM), evoked currents in GABA_A (969 ± 208pA, mean ± SD, n=384) but not wild-type HEK293 cells (<50pA), that reversed close to E_Cl (-56mV). Concentration-response curve analysis yielded a pEC₅₀ value of 5.4 ± 0.1 and n_H of 1.5 ± 0.3 (n=12). Muscimol and isoguvacine also elicited currents with pEC₅₀ values of 5.9 ± 0.1 (n=10) and 4.4 ± 0.1 (n=10), respectively. Positive modulators augmented the GABA EC₂₀ response (1μM) with pEC₅₀ and % max potentiation values for diazepam of 7.0 ± 0.2 and 291 ± 51% (n=10), zolpidem of 6.8 ± 0.2 and 378 ± 48% (n=10), pentobarbital of 4.5 ± 0.2 and 811 ± 81% (n=10) and tracazolate of 5.3 ± 0.1 and 571 ± 99% (n=2). GABA responses were inhibited by bicuculline, picrotoxin and gabazine with pIC₅₀ values of 4.8 ± 0.1 (n=6), 5.6 ± 0.1 (n=6) and 5.7 ± 0.1 (n=6), respectively. Bicuculline and gabazine produced concentration-dependent, parallel rightward displacement of GABA curves with pA₂ and slope values of 5.7 and 1.0 for bicuculline and 6.7 and 1.0 for gabazine, indicating competitive antagonism. Picrotoxin depressed the GABA response with minimal shift in the pEC₅₀ value implying a non-competitive antagonism. In conclusion, despite the inability to resolve the peak GABA responses, PPC can quantify agonist, modulator and antagonist pharmacology in the GABA_A cell line. Agonist and modulator potencies were 3-10-fold greater than expected, with steep Hill slopes, presumably reflecting concentration-dependent desensitisation that serves to underestimate the true response curve asymptote. This is a significant technical limitation. For antagonists and blockers, where such kinetic constraints are less important, our Schild analysis and ability to discern competitive and non-competitive antagonism are very encouraging. These data suggest that PPC may be a valuable approach for screening GABA_A receptors and other slow ligand-gated ion channels.