Institute for Neural Signal Transduction, Center for Molecular Neurobiology, University Hospital Hamburg-Eppendorf, Falkenried 94, D-20253 Hamburg, Germany.
Endocrinology. 2010 Mar;151(3):1079-88. doi: 10.1210/en.2009-0718. Epub 2010 Jan 12.
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.
促性腺激素细胞中 LH 的分泌是由 GnRH 诱导的细胞内 Ca(2+)浓度增加(Ca(2+))引发的。Ca(2+)的增加是细胞内储存的 Ca(2+)释放和通过电压依赖性 Ca(2+)通道的 Ca(2+)内流的结果。在这里，我们描述了在原代小鼠促性腺激素细胞中的一种与 ether-à-go-go 相关基因 (erg) K(+)电流及其在控制 Ca(2+)内流中的可能作用。为了检测促性腺激素细胞，我们使用了一种 GnRH 受体表达细胞荧光标记的基因敲入小鼠品系。在 80-90%的促性腺激素细胞中记录到 erg K(+)电流。erg 电流的阻断剂 E-4031 将静息电位去极化 5-8 mV，并导致 Ca(2+)增加，该增加被硝苯地平所消除。GnRH 通过降低最大 erg 电流以及在一些细胞中另外通过将激活曲线移向更正的电位来抑制 erg 电流。总之，erg 电流有助于维持促性腺激素细胞的静息电位，从而通过限制 Ca(2+)内流来确保低 Ca(2+)。此外，erg 通道通过未知的信号级联被 GnRH 调节。
