Repetitive activation of postsynaptic GABA(A) receptors by rapid, focal agonist application onto intact rat striatal neurones in vitro

GABA(A) receptor-mediated Cl- currents were evoked by rapid and short (0.75-1.5 ms), focal iontophoretic applications of GABA to proximal dendrites of cultured striatal neurones. The mean amplitude (232+/-21.0 pA) was in the range of large miniature inhibitory postsynaptic currents (mIPSCs), while the 10-90% rise times (3.4+/-0.20 ms) and the time constants of decay (60.0+/-8.4 ms) were three times slower. Responses to paired-pulse application of GABA at inter-pulse intervals (IPIs) of 30, 100 and 300 ms showed no depression of the second response (R2) relative to the first (R1). At short IPIs, at which RI and R2 showed temporal summation, the net amplitude of R2 (R2(net)) was partially occluded. Lowering the iontophoretic intensity during paired-pulse application at an IPI of 30 ins reduced R1 by 69.5+/-3.3%, while occlusion of R2(net) decreased significantly, indicating that the receptor occupancy had been lowered. During the course of ten pulses of GABA at 10 Hz, responses declined by 8.7+/-3.9%, which probably reflects slow cumulative desensitization. In conclusion, rapid focal iontophoresis of exogenous GABA onto GABA(A) receptors does not result in activity-dependent depression of the postsynaptic response. This result suggests that fast desensitization is unlikely to occur during repetitive GABA(A) receptor-mediated synaptic transmission in striatal neurones.