DESENSITIZED STATES PROLONG GABA(A) CHANNEL RESPONSES TO BRIEF AGONIST PULSES

We studied the role of desensitization at inhibitory synapses by compa ring nonequilibrium GABA(A) channel gating with inhibitory postsynapti c currents (IPSCs). Currents activated by brief pulses of 1-10 mM GABA to outside-out patches from cultured hippocampal neurons mimicked GAB A-mediated IPSCs. Although the average open time of single GABA(A) cha nnels following brief pulses was less than 10 ms, channels entered lon g (tau = 38-69 ms) closed states and subsequently reopened. Movement t hrough these states resulted in paired-pulse desensitization. The time required for deactivation after removal of agonist also increased in proportion to the extent of desensitization. These results suggest tha t visits to desensitized states buffer the channel in bound conformati ons and underlie the expression of long-lasting components of the IPSC . Reopening after GABA(A) receptor desensitization may thus enhance in hibitory synaptic transmission by prolonging the response to a brief s ynaptic GABA transient.