Effects of progesterone, epipregnanolone and RU 38486 on potassium uptake in cultured cortical neurons

Abstract

It was previously reported that progesterone and its metabolites influence electrical properties of the CNS in many different ways. In the present study we elicited the effects of progesterone, its 5β reduced metabolite epipregnanolone and the anti-progestin compound RU 38486 on potassium uptake in cultured cortical neurons. K⁺ was substituted by the tracer substance ⁸⁶Rb. When hormone treatment (10⁻⁹−10⁻⁷ M/1) was performed for 3 days, addition of progesterone and epipregnanolone led to a significant decrease of ⁸⁶Rb uptake whereas treatment with RU 38486 markedly increased ⁸⁶Rb uptake. The effect of the anti-progestin could be reversed by the addition of increasing amounts of progesterone. Hormone actions were dose-dependent and most distinct when performed from the very first day of culture. Short-term (15min) hormone treatment of neurons did not significantly alter ⁸⁶Rb uptake. These findings suggest a specific receptor mediated progestin action which, in a long-term course, controls potassium uptake across excitable membranes.