Estrogen transiently increases delayed rectifier, voltage-dependent potassium currents in ovine gonadotropes

Treatment of gonadotropes with estrogen (E) changes the electrophysiologica l response to gonadotropin-releasing hormone (GnRH) such that the cells are hyperpolarised immediately after stimulation with GnRH and then generate a ction potentials more frequently than non-E-treated cells. We investigated the role of K+ current in this altered response to GnRH using cultures of e we pituitary cells enriched for gonadotropes, K+ current density was measur ed using nystatin-perforated whole-cell recordings in the voltage clamp mod e. 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 curr ent in these cells flows predominantly through voltage-dependent, delayed r ectifier 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 wa s maximal after 16-20 h, The unit K+ current values returned to pre-treatme nt 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 in crease 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 v itro and in vivo. We conclude that the increase in K+ current may be an imp ortant part of the mechanism whereby E acts on gonadotropes to facilitate t he LH surge which triggers ovulation.