Ion Channels of Pituitary Gonadotrophs and Their Roles in Signaling and Secretion.
Ion Channels of Pituitary Gonadotrophs and Their Roles in Signaling and Secretion.
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DOI：
10.3389/fendo.2017.00126
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发表时间：
2017
影响因子：
5.2
通讯作者：
Zemkova H
中科院分区：
文献类型：
--
作者：
Stojilkovic SS;Bjelobaba I;Zemkova H
促性腺激素细胞是垂体前叶的嗜碱性细胞，其特化为响应细胞内钙浓度升高而分泌促性腺激素。这些细胞自发地激发动作电位（AP），加上电压门控钙内流的幅度不足，触发促性腺激素释放。促性腺激素细胞的自发兴奋性反映了其质膜（PM）上电压门控钠、钙、钾、非选择性阳离子传导和氯离子通道的表达。这些细胞还在PM表达超极化激活和环核苷酸门控阳离子通道，以及分别由γ-氨基丁酸（GABA）、乙酰胆碱（ACh）和ATP门控的GABAA、烟碱和嘌呤能P2 X通道。这些通道的激活导致起搏活性的启动或放大、钙内流的促进和胞吐途径的激活。促性腺激素细胞也在内质网膜上表达钙离子传导通道，这些通道由三磷酸肌醇和细胞内钙离子门控。这些通道被下丘脑促性腺激素释放激素（GnRH）有效激活，而被几种旁分泌钙动员激动剂（包括垂体腺苷酸环化酶激活肽、内皮素、ACh、加压素和催产素）激活的效力较低。这些通道的激活引起振荡钙释放和快速促性腺激素释放，伴随着从单个AP的紧张性放电到周期性爆发型电活动的转变，这解释了持续的钙信号传导和促性腺激素分泌。本文综述了我们目前对离子通道作为促性腺激素细胞信号分子的认识，GnRH和旁分泌激动剂在其门控中的作用，以及通道间的串扰。
Gonadotrophs are basophilic cells of the anterior pituitary gland specialized to secrete gonadotropins in response to elevation in intracellular calcium concentration. These cells fire action potentials (APs) spontaneously, coupled with voltage-gated calcium influx of insufficient amplitude to trigger gonadotropin release. The spontaneous excitability of gonadotrophs reflects the expression of voltage-gated sodium, calcium, potassium, non-selective cation-conducting, and chloride channels at their plasma membrane (PM). These cells also express the hyperpolarization-activated and cyclic nucleotide-gated cation channels at the PM, as well as GABAA, nicotinic, and purinergic P2X channels gated by γ-aminobutyric acid (GABA), acetylcholine (ACh), and ATP, respectively. Activation of these channels leads to initiation or amplification of the pacemaking activity, facilitation of calcium influx, and activation of the exocytic pathway. Gonadotrophs also express calcium-conducting channels at the endoplasmic reticulum membranes gated by inositol trisphosphate and intracellular calcium. These channels are activated potently by hypothalamic gonadotropin-releasing hormone (GnRH) and less potently by several paracrine calcium-mobilizing agonists, including pituitary adenylate cyclase-activating peptides, endothelins, ACh, vasopressin, and oxytocin. Activation of these channels causes oscillatory calcium release and a rapid gonadotropin release, accompanied with a shift from tonic firing of single APs to periodic bursting type of electrical activity, which accounts for a sustained calcium signaling and gonadotropin secretion. This review summarizes our current understanding of ion channels as signaling molecules in gonadotrophs, the role of GnRH and paracrine agonists in their gating, and the cross talk among channels.