IGF, Université de Montpellier, CNRS, INSERM, Montpellier, France.
LabEx 'Ion Channel Science and Therapeutics', Montpellier, France.
FASEB J. 2021 May;35(5):e21400. doi: 10.1096/fj.202000841RR.
Anterior pituitary endocrine cells that release hormones such as growth hormone and prolactin are excitable and fire action potentials. In these cells, several studies previously showed that extracellular sodium (Na ) removal resulted in a negative shift of the resting membrane potential (RMP) and a subsequent inhibition of the spontaneous firing of action potentials, suggesting the contribution of a Na background conductance. Here, we show that the Na leak channel NALCN conducts a Ca - Gd -sensitive and TTX-resistant Na background conductance in the GH cell line, a cell model of pituitary endocrine cells. NALCN knockdown hyperpolarized the RMP, altered GH cell electrical properties and inhibited prolactin secretion. Conversely, the overexpression of NALCN depolarized the RMP, also reshaping the electrical properties of GH cells. Overall, our results indicate that NALCN is functional in GH cells and involved in endocrine cell excitability as well as in hormone secretion. Indeed, the GH cell line suitably models native pituitary cells that display a similar Na background conductance and appears as a proper cellular model to study the role of NALCN in cellular excitability.
分泌生长激素和催乳素等激素的垂体前叶内分泌细胞具有兴奋性，可以产生动作电位。在此之前的几项研究表明，细胞外钠离子（Na+）的去除会导致静息膜电位（RMP）负移，并随后抑制动作电位的自发发放，提示存在 Na+背景电导的贡献。在这里，我们表明 NALCN 钠泄漏通道在 GH 细胞系（一种垂体内分泌细胞的细胞模型）中传导一种 Ca-Gd-敏感和 TTX-抵抗的 Na+背景电导。NALCN 的敲低使 RMP 超极化，改变了 GH 细胞的电特性并抑制催乳素的分泌。相反，NALCN 的过表达使 RMP 去极化，也重塑了 GH 细胞的电特性。总的来说，我们的结果表明 NALCN 在 GH 细胞中具有功能，参与内分泌细胞的兴奋性以及激素的分泌。事实上，GH 细胞系适当地模拟了具有类似 Na+背景电导的天然垂体细胞，并且作为研究 NALCN 在细胞兴奋性中的作用的合适细胞模型。
