Fig. 3.

Abl kinase activity sustains nAChR-mediated synaptic activity. A to C, Abl kinase inhibition with 10 μM STI571 reduced the frequency and amplitude of sEPSCs. A, example whole-cell current records from neurons in sham-treated (Control, top) and STI571-treated (STI571, bottom) 4-day CG cultures, calibration bars depicting 20 pA and 250 ms. B and C, cumulative histograms of mean sEPSC frequencies (F_s, B) and amplitudes (A_s, C) acquired in individual experiments from control neurons (□,○; N_T,s = 3495 EPSCs, n = 35 neurons, N = 7 cultures) and neurons treated with 10 μM STI571 (■, ●; N_T,s = 529 EPSCs, n = 16 neurons, N = 5 cultures). STI571 treatments of 1 and 24 h gave similar results, and the data have been combined. Inset bar graphs depict relative sEPSC frequencies and amplitudes (F_s* and A_s*, respectively), representing F_s and A_s values normalized to controls from the same experiments (*, p < 0.05 by Student's t test). D and E, Abl kinase inhibition reduced synaptic activity in a dose-dependent fashion. STI571 applied for 24 h at increasing concentrations progressively reduced F_s* (■, D) and A_s* (●, E). Each point in D and E represents the F_s* or A_s* value (± S.E.M.) from neurons treated with 1, 3, or 10 μM STI571 (n = 10–14) relative to untreated control neurons (n = 13–17) tested in the same experiments (N = 5). The STI571 concentrations predicted to achieve 50% F_s* and A_s* inhibition (IC₅₀) were 1.0 and 1.8 μM, respectively (arrowheads).