Gonadotropin-releasing hormone inhibits ether-à-go-go-related gene K+ currents in mouse gonadotropes.

Secretion of LH from gonadotropes is initiated by a GnRH-induced increase in intracellular Ca(2+) concentration (Ca(2+)). This increase in Ca(2+) is the result of Ca(2+) release from intracellular stores and Ca(2+) influx through voltage-dependent Ca(2+) 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 Ca(2+) 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 Ca(2+), 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 Ca(2+) by restricting Ca(2+) influx. In addition, the erg channels are modulated by GnRH by an as-yet unknown signal cascade.