Estrogen Transiently Increases Delayed Rectifier, Voltage-Dependent Potassium Currents in Ovine Gonadotropes

Abstract

Treatment of gonadotropes with estrogen (E) changes the electrophysiological response to gonadotropin-releasing hormone (GnRH) such that the cells are hyperpolarised immediately after stimulation with GnRH and then generate action potentials more frequently than non-E-treated cells. We investigated the role of K⁺ current in this altered response to GnRH using cultures of ewe pituitary cells enriched for gonadotropes. K⁺ current density was measured using nystatin-perforated whole-cell recordings in the voltage clamp mode. Treatment of cells with E for 16–20 h significantly (p < 0.01) increased the unit K⁺ current to 180% of that in vehicle-treated cells. Outward current in these cells flows predominantly through voltage-dependent, delayed rectifier K⁺ channels (I_K), and E alters the magnitude of this current. The effect of E to increase the K⁺ current was dose- and time-dependent and was maximal after 16–20 h. The unit K⁺ current values returned to pre-treatment levels after 36 h of E treatment. Several cells were studied both before and after E treatment and the average effect of E on these cells was to increase the unit K⁺ current by 90%. The time-course of the effect of E on K⁺ current density is the same as the effect of E to increase LH release in vitro and in vivo. We conclude that the increase in K⁺ current may be an important part of the mechanism whereby E acts on gonadotropes to facilitate the LH surge which triggers ovulation.