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Figure 4. Mechanism of zolpidem modulatory actions at α1β3 and α1β3γ2 GABAA receptors.Xenopus laevis oocytes were injected with cRNA and subjected to two-electrode voltage clamp electrophysiology as described in the methods. (A–C) Full GABA concentration-response relationships were obtained in presence of the indicated concentrations of zolpidem (Zolp) at receptors stemming from injection of cRNA of free subunits (A,C) or a concatenated construct (B). Baseline subtracted GABA + zolpidem peak current amplitudes were normalized to a maximal GABA control response (3 mM) in the same oocytes. Averaged normalized data points are depicted as means ± S.E.M. as a function of the GABA concentration and fitted to the Hill equation with regression results are presented in Table 1. Each data point represents experiments from n = 5–7 oocytes from ≥2 batches. GABA concentration response relationships in absence of zolpidem (from Fig. 1) are included for comparison. (D) The depiction of α1β3 GABAA receptor stoichiometries from Fig. 2D was modified to indicate zolpidem binding in the α1(+)-α1(−) subunit interface (red/green arrowhead). Image published in: Che Has AT et al. (2016) Copyright © 2016, Macmillan Publishers Limited. This image is reproduced with permission of the journal and the copyright holder. This is an open-access article distributed under the terms of the Creative Commons Attribution license Larger Image Printer Friendly View

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