DESENSITIZATION AND NONCOMPETITIVE BLOCKADE OF GABA(A) RECEPTORS IN VENTRAL MIDBRAIN NEURONS BY A NEUROSTEROID DEHYDROEPIANDROSTERONE-SULFATE

Dehydroepiandrosterone sulfate (DHEAS) blocked the GABA(A) receptor no ncompetitively in neurons grown in primary culture from the ventral mi dbrains of fetal rats. The apparent dissociation constant for this blo ckade was 4.5 mu M, and one molecule of DHEAS was sufficient to block the receptor. The affinity of the blocked receptor for GABA was dimini shed by about one half. The findings that the DHEAS caused no rectific ation of chloride currents and that it did not shorten the durations o f open ion channels indicated that DHEAS did not act by occluding open ion channels. Neither did it diminish their conductance. DHEAS accele rated desensitization in at least one population of receptors, diminis hed the amplitudes of inhibitory postsynaptic currents, and shortened their decay time constants in a concentration dependent manner.