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+)](i)). This increase in [Ca(2+)](i) 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+)](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 [Ca(2+)](i) by restricting Ca(2+) influx. In addition, the erg channels are modulated by GnRH by an as-yet unknown signal cascade.
Hirdes
Wiebke
W
Institute for Neural Signal Transduction, Center for Molecular Neurobiology, University Hospital Hamburg-Eppendorf, Falkenried 94, D-20253 Hamburg, Germany. whirdes@zmnh.uni-hamburg.de
Dinu
Crenguta
C
Bauer
Christiane K
CK
Boehm
Ulrich
U
Schwarz
Jürgen R
JR
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D045604:Extracellular Fluid / Q000378:metabolism; D052681:Gonadotrophs / Q000378:metabolism*; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism* / Q000494:pharmacology; D007424:Intracellular Fluid / Q000378:metabolism; D007986:Luteinizing Hormone / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
D051638:Ether-A-Go-Go Potassium Channels; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone; D002118:Calcium