not-yet-known not-yet-known not-yet-known unknown Figure 7. MRS5474, through A3R activation, selectively enhances GABAergic currents in epileptic human hippocampal samples . The panel in A shows representative currents evoked by GABA (500µM, applied as indicated by the white horizontal bars) recorded before (black trace) and after (red trace) incubation with MRS5474 (5 μM, for 2h 30 min) and MRS1523 (third row, 10 μM) from oocytes injected with membranes prepared from epileptic patient tissue samples (TLE, left) or control (CTRL, right); each row shows recordings from the same oocyte. B : Concentration-response curves obtained in a non-cumulative manner; the ordinates represent the percentage change of the amplitude of GABA-evoked responses after incubation with different concentrations of MRS5474, as indicated in the abscissae; 100% represents the amplitude of currents recorded before exposure to MRS5474 in the same oocytes. The raw amplitude values before and after incubation for each concentration are the following: [0.05 μM], from 43.0 ± 10.0 nA , before incubation to 46.7 ± 13.8 nA , after incubation; n=8; # 1, 2; [0.5 μM], from 68.5 ± 10.0 nA, before incubation to 78.6 ± 15.6 nA , after incubation; n=8; # 2,3; [1.5 μM] from 41.4 ± 4.6 nA , before incubation to 52.8 ± 6.0 nA , after incubation; n=8; # 1, 2; [5 μM] from 47.3 ± 8.9 nA , before incubation to 71.0 ± 16.9, after incubation; n=15; # 1–3; [10 μM] from 43.6 ± 6.5 nA , before incubation to 62.5 ± 6.3, after incubation; n=8; # 1-3. C : Comparison (in another set of experiments), between the effect (as % change in the ordinates) in current amplitude caused by a submaximal concentration of MRS5474 (1.5 µM) in the absence (n=8 oocytes) and in the presence (n=11) of the A3R antagonist, MRS1523 (10 µM). D : Comparison between the effects of a near maximal concentration of MRS5474 (5µM) in oocytes injected with membrane samples from epileptic patients (same data as in B , n=15) and from oocytes injected with membranes from controls (n=10, #4). In B -D , values are expressed as mean ± SEM. Statistical analysis shown in B represents the comparison between current amplitude before and after MRS5474 (two tailed paired student’s t-test) and in C-D represents the comparison between the pooled data in the two conditions shown in each panel (two tailed unpaired Student’s t test). For all panels: *P<0.05, **P<0.01, ***P<0.005, ****P<0.0001.