Slow desensitization regulates the availability of synaptic GABA(A) receptors

At central synapses, a large and fast spike of neurotransmitter efficiently activates postsynaptic receptors. However, low concentrations of transmitt er can escape the cleft and activate presynaptic and postsynaptic receptors . We report here that low concentrations of GABA reduce IPSCs in hippocampa l neurons by preferentially desensitizing rather than opening GABA(A) chann els. GABA transporter blockade also caused desensitization by locally eleva ting GABA to similar to1 muM. Recovery of the IPSC required several seconds , mimicking recovery of the channel from slow desensitization. These result s indicate that low levels of GABA can regulate the amplitude of IPSCs by p roducing a slow form of receptor desensitization. Accumulation of channels in this absorbing state allows GABA(A) receptors to detect even a few molec ules of GABA in the synaptic cleft.