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Figure 3. Zolpidem modulation of GABA-evoked currents from 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. Control currents (Icontrol) were evoked using a GABA concentration corresponding to ~EC5–10 and modulation by zolpidem was evaluated by co-applications with GABAcontrol. (A–C) Representative GABA-evoked current traces from oocytes injected with the denoted cRNA mixtures. Bars above each trace indicate GABA, zolpidem (Zolp) and flumazenil (Flu) concentrations and application periods. Dotted lines indicate the peak current amplitude by GABAcontrol and “/” a wash period. For the specific traces, zolpidem had no robust effects at receptors from α1 + β3 (1:1) injection (A), but showed 130% modulation at receptors from α1 + β3 (30:1) injection which was inhibited 95% by co-application of flumazenil (B). Zolpidem likewise modulated receptors from injection of α1 + β3 + γ2 (1:1:5) by 160% which could be inhibited 85% by flumazenil (C). (D,E) Concentration-response relationships of zolpidem modulation of GABAcontrol-evoked currents at α1β3 or α1β3γ2 receptors stemming from injecting the indicated cRNA mixtures using free subunits (D) or a concatenated β3-α1 construct (E). Average modulatory values were depicted as means ± S.E.M as a function of the zolpidem concentration and fitted to the Hill equation by non-linear regression. Each data point represents experiments from n = 5–7 oocytes from ≥2 batches and regression results are presented in Table 1.

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

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