Figure 5. The src-family tyrosine kinase inhibitor PP1 occludes the effect of AMPAR inhibition.

A and B, 10 μm PP1 (+0.1% DMSO) was added to the internal solution and allowed to diffuse for 20 min into the postsynaptic Purkinje cell via the patch pipette. C and D, interleaved control experiments with 0.1% DMSO added to the internal solution. A and C, average amplitude plot of first AMPA EPSC and mGluR EPSC normalised to the response at the beginning of AMPA block. A, with PP1, there is no significant increase of the sEPSC amplitude following NBQX application. C, with DMSO only, there is a large increase of the mGluR sEPSC following NBQX application. B and D show average traces with no significant increase when PP1 is infused into the cell and a large increase for the DMSO-only experiment. E, bar graph of average amplitude ±s.e.m. of mGluR sEPSC for cells recorded with PP1 supplemented internal (black) and control with DMSO (grey). Control values were taken at 20 min whole cell recording and NBQX values at the peak of the effect. With PP1 the control value was increased and there was no further effect of NBQX whereas in interleaved DMSO recordings there was a potentiation of the sEPSC. The increased sEPSC in PP1 was significantly different to DMSO controls, P < 0.01. NBQX significantly increased the sEPSC in DMSO control experiments (P < 0.05) but not with internal PP1. F, bar graph of average amplitude ±s.e.m. of mGluR sEPSC in control, during extracellular application of 10 μm PP1 and addition of 1 μm NBQX. Extracellular application of PP1 had no effect on the sEPSC.