Patch clamp electrophysiology techniques and an ultrafast ligand excha
nge system (100 mu s exchange time) were used to study opening rates o
f GABA-A receptor chloride channels in excised outside-out patches of
fetal rat cortical neurons in culture. Receptor activation kinetics we
re studied using GABA (0.5 mu M-10 mM) using rapid ligand exchanges. P
atches contained 5-25 channels and were voltage clamped at -75 mV in s
ymmetrical chloride solutions at room temperature. Responses were anal
yzed individually and as ensemble averages for each patch. Current ris
e times (10-90%) decreased with increased GABA concentration to a mini
mum of about 0.5 ms at 1 and 10 mM. Rates of channel activation at sat
urating GABA concentrations were similar to that recorded for miniatur
e inhibitory currents at GABA. synapses in these neurons. These data s
uggest that the synaptic concentration of GABA to activate GABA-A rece
ptors in these neurons is at least 1 mM.