Fig. 4.
Abl kinase inhibition selectively reduces the quantal size of nAChR-dependent synaptic events. A, cumulative histogram of mean mEPSC amplitudes (as) acquired in the presence of 1 μM TTX from control neurons (▵; nT,m = 1153 mEPSCs, n = 19 neurons) and neurons treated with 10 μM STI571 (▴; nT,m = 226 mEPSCs, n = 20 neurons) from the same cultures (N = 5). Treatments with 10 μM STI571 for 1 and 24 h gave similar results, and the data have been pooled. The inset depicts sample mEPSCs (top) and mean amplitudes (bottom) from control and treated neurons. as* represents mean mEPSC amplitude for treated relative to sham-treated control neurons from the same experiments (*, p < 0.05 by Student's t test). B, Abl kinase inhibition with STI571 applied at increasing concentrations progressively reduced mEPSC amplitude but failed to alter frequency. Each point represents the mEPSC amplitude or frequency (± S.E.M.) from neurons treated with 1, 3, or 10 μM STI571 (n = 9–12) relative to untreated control neurons (n = 3–5) (as*, ● or fs*, ■) assayed in the same experiments (N = 5). The STI571 concentration predicted to achieve 50% inhibition (IC50) of as* was ≈2.0 μM. C and D, AFK inhibition reduces the amplitude of stimulus evoked EPSCs. Records in C depict sample eEPSCs (●) and failures (○) from control (top) and STI571-treated neurons after fascicle stimulation (arrow). Calibrations represent 50 pA and 5 ms. Bar graph in D represents cumulative eEPSC amplitudes from STI571-treated neurons (n = 6; 10 μM) relative to untreated control neurons (n = 6) (Ae*) tested in the same experiments (N = 2). *, p < 0.05 by Student's t test.