Figure 5: Shisa6 decreases AMPAR deactivation rate and desensitization rate, enhances the steady-state current and slows recovery from desensitization.
(a) Peak-scaled example traces of whole-cell recording from HEK293 cells expressing heteromeric AMPAR channels in the absence (grey) or presence (red) of Shisa6. Currents were evoked by direct application of 1 mM glutamate during 1 ms. (b) Bar graphs (mean±s.e.m.) summarize changes in rise time (1.06±0.06 versus 1.20±0.06 ms, P=0.101) and decay time (4.50±0.28 versus 5.81±0.35 ms, P=0.005) of AMPAR currents mediated by heteromeric AMPARs in HEK293 cells in the presence and absence of Shisa6. (c) Peak-scaled example trace of whole-cell recordings from HEK293 cells expressing a heteromeric AMPAR channel in the absence (grey) or presence (red) of Shisa6. Currents were evoked by direct application of 1 mM glutamate during 1 s. (d) Bar graphs (mean±s.e.m.) summarize changes in rise time (1.60±0.08 versus 2.04±0.12 ms, P=0.072), desensitization time constant and steady-state AMPAR-mediated currents. (norm., normalized) *P<0.050, **P<0.010, ***P<0.001 (t-test). (e) Example trace of repeated 1-ms glutamate application from HEK293 cells expressing a heteromeric AMPAR channel in the absence (grey) or presence (red) of Shisa6. (f) Recovery of desensitization (two 1-ms glutamate application with inter-pulse interval of 20, 50, 100, 200, 300, 400, 500, 750, 1,000 and 3,000 ms) from HEK293 cells expressing a heteromeric AMPAR channel in the absence (grey) or presence (red) of Shisa6. Inset (left) shows recovery up to 200 ms. In the presence of Shisa6, recovery is slower, yielding an increase in τrecovery (right inset). ***P<0.001.
