Mechanism underlying the effect of pregnenolone sulfate on the kainate-induced current in cultured chick spinal cord neurons

The effect of the neurosteroid pregnenolone sulfate on the kainate receptor-mediated response was studied in cultured chick spinal cord neurons using the whole-cell voltage-clamp recording technique. Pregnenolone sulfate rapidly and reversibly inhibits the kainate-induced current in a dose-dependent manner, with an EC(50) of 67 mu M and maximal inhibition of 38%. Inhibition by pregnenolone sulfate of the kainate response is not attenuated by increasing concentrations of kainate, suggesting that the blocking action of pregnenolone sulfate is non-competitive. Antagonism of the kainate response by pregnenolone sulfate is neither agonist- nor voltage-dependent, indicating that pregnenolone sulfate does not act as an open-channel blocker. Furthermore, our results demonstrate that pregnenolone sulfate and 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine (GYKI 52466; a potent non-competitive kainate antagonist) do not act through a common site. (C) 1997 Elsevier Science Ireland Ltd.