Figure 1.

VU573 inhibits mGluR8-activated Kir3.1/3.2 channel activity in thallium flux assays. (A) Representative FluoZin-2 fluorescence traces recorded from HEK-293 cells stably expressing mGluR8 and Kir3.1/3.2 before and after co-application of thallium and different doses of glutamate (shaded box). From an 11-point glutamate concentration–response curve (not shown), the glutamate concentration evoking approximately 80% (EC₈₀) of the maximal response (EC_max) was determined and used for subsequent experiments. (B) Representative traces for changes of Tl⁺-induced FluoZin-2 fluorescence following 20 min pre-treatment of cells with the indicated concentrations of VU573 and subsequent thallium and glutamate-EC₈₀ addition (shaded box). (C) Mean ± SEM concentration–response curve for VU573-dependent inhibition of Kir3.1/3.2 (n = 3). The chemical structure of VU573 is shown in the inset. (D) Representative FluoZin-2 fluorescence traces recorded from monoclonal Kir1.1-S44D expressing cells cultured overnight in absence (−Tet) or presence (+Tet) of Tetracycline. (E) Representative traces for changes of Tl⁺-induced FluoZin-2 fluorescence following pre-treatment of cells with the indicated concentrations of VU573 and then exposed to thallium (shaded box). (F) Mean ± SEM concentration–response curve for VU573-dependent inhibition of Kir1.1-S44D (n = 3).