Figure 7. The kinetic modelling of the experimental data.

The scheme in A was used for the kinetic modelling. It includes agonist-free (R), agonist-bound (RA/RAA) open (R*AA) and desensitized (RAAD) states of the channel and its complexes with a blocker (symbol B is added). In the model the blocking molecule is able to permeate through the open channel (k_perm component of the unbinding rate constant) and escape from the closed states by leaking into the cytoplasm (k_esc unipolar arrows). B, the calculated kainate-activated current and its inhibition by 5 μm IEM-1925. The continuous presence of agonist IEM-1925 induces deep block of the current (compare with Fig. 3A). C, the model prediction for the response evoked by 1 ms pulse of 1 mm glutamate (control) imitating eEPSC and its inhibition by 5 μm IEM-1925 at two different stimulation frequencies. In agreement with the experimental data (see Fig. 4A and B), the increase of stimulation frequency results in enhancement of block. D, the calculated eEPSC has smaller amplitude in the presence of bath-applied agonist (100 μm) than in control. In these conditions 5 μm IEM-1925 produces strong block of calculated EPSCs even at 0.1 Hz simulation (compare with Fig. 6D and E).