PATCH-CLAMP ANALYSIS OF DIRECT STEROIDAL MODULATION OF GLUTAMATE RECEPTOR-CHANNELS

Steroid hormones regulate the neuroendocrine and behavioral functions of the brain by using a number of diverse cellular mechanisms. Many st eroids exert rapid electrophysiological effects on neurons, involving specific interactions with membrane components, such as neurotransmitt er receptors. Previous studies suggest that the steroids, estrogen and pregnenolone sulfate (PS), might directly modulate glutamate receptor s. The present experiments utilized patch-clamp recording of glutamate receptor-channels in excised membrane patches to test for direct modu lation by these steroids. Characteristic single-channel activity from N-methyl-D-aspartate (NMDA) receptors could be elicited in both inside -out and outside-out patches excised from acutely dissociated hippocam pal neurons. PS, but not 17 beta-estradiol, increased the open probabi lity of NMDA channel activity in inside-out and outside-out patches. T he PS-induced increase in open probability could be attributed to an i ncrease in both frequency of opening and mean open time of the NMDA re ceptor, though the effect on frequency of opening was more prominent. The non-NMDA agonist, kainate, induced continuous shifts and increased noise in the baseline current of outside-out patches, but rarely acti vated clearly resolvable single-channel openings. 17 beta-estradiol an d PS had no apparent effect on the kainate-induced currents. These fin dings suggest that some steroids can directly modulate glutamate recep tors, but other steroids may utilize indirect mechanisms for regulatin g glutamatergic synaptic transmission.