Gonadotropin-Releasing Hormone Inhibits Ether-à-Go-Go-Related Gene K+ Currents in Mouse Gonadotropes

Abstract

Secretion of LH from gonadotropes is initiated by a GnRH-induced increase in intracellular Ca2+ concentration ([Ca2+]i). This increase in [Ca2+]i is the result of Ca2+ release from intracellular stores and Ca2+ influx through voltage-dependent Ca2+ channels. Here we describe an ether-à-go-go-related gene (erg) K+ current in primary mouse gonadotropes and its possible function in the control of Ca2+ influx. To detect gonadotropes, we used a knock-in mouse strain, in which GnRH receptor-expressing cells are fluorescently labeled. Erg K+ currents were recorded in 80–90% of gonadotropes. Blockage of erg currents by E-4031 depolarized the resting potential by 5–8 mV and led to an increase in [Ca2+]i, which was abolished by nifedipine. GnRH inhibited erg currents by a reduction of the maximal erg current and in some cells additionally by a shift of the activation curve to more positive potentials. In conclusion, the erg current contributes to the maintenance of the resting potential in gonadotropes, thereby securing a low [Ca2+]i by restricting Ca2+ influx. In addition, the erg channels are modulated by GnRH by an as-yet unknown signal cascade.