Ovarian acetylcholine and ovarian KCNQ channels: Insights into cellular regulatory systems of steroidogenic granulosa cells
Ovarian acetylcholine and ovarian KCNQ channels: Insights into cellular regulatory systems of steroidogenic granulosa cells
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DOI：
10.1016/j.lfs.2007.01.022
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发表时间：
2007-05-30
期刊：
影响因子：
6.1
通讯作者：
Mayerhofer, A.
中科院分区：
文献类型：
--
作者：
Kunz, L.;Roggors, C.;Mayerhofer, A.
乙酰胆碱(ACh)可能是一种卵巢信号分子，因为ACh是由来自有腔卵泡的非神经元颗粒细胞(GC)产生的，也可能是由生长卵泡中的体内对应细胞产生的。此外，M受体(MR)存在于GC膜和培养的人GC中，许多MR介导的作用已被描述，包括调节增殖和缝隙连接通讯。重要的是，毒扁豆碱刺激升高细胞内钙水平，从而打开钙激活的钾通道(BKCa)，引起膜超极化。在人GC的电生理实验过程中，我们还观察到ACh类似物(卡巴胆碱)对外向钾电流的可逆抑制作用。这种电流让人想起神经系统中所描述的所谓的M-电流，其中M-电流的调节是众所周知的。事实上，KCNQ受体阻滞剂XE991对电流是敏感的，并且通过RT-PCR和免疫组织化学方法在大卵泡中检测到可能的潜在通道KCNQ1(K(V)7.1/K(V)LQT1)。XE991对该通道的药理抑制阻断了促性腺激素刺激的类固醇的产生和促进细胞增殖，即卵巢中GC的基本过程。假设ACh在体内有类似的作用，该通道可能是生理GC功能的关键调节因子，与新的卵巢内信号分子ACh的作用有关。(C)2007 Elsevier Inc.保留所有权利。
Acetylcholine (ACh) may be an ovarian signaling molecule, since ACh is produced by non-neuronal granulosa cells (GCs) derived from the antral follicle, and likely also by their in vivo counterparts in the growing follicle. Furthermore, muscarinic ACh receptors (MR) are present in GC membranes and in cultured human GCs a number of MR-mediated actions have been described, including regulation of proliferation and gap junctional communication. Importantly, muscarinic stimulation elevates intracellular calcium levels, thereby opening a calcium-activated potassium channel (BKCa) and causing membrane hyperpolarization. In the course of electrophysiological experiments with human GCs we also observed a reversible inhibitory action of an ACh analogue (carbachol) on an outward potassium current. This current is reminiscent of a so-called M-current described in neuronal systems, of which muscarinic regulation is well-known. Indeed, the current is sensitive to the specific KCNQ blocker XE991 and a possible underlying channel, KCNQ1 (K(v)7.1/K(v)LQT1) was detected by RT-PCR in GCs and by immunohistochemistry in large ovarian follicles. Pharmacological inhibition of the channel by XE991 blocked gonadotropin-stimulated steroid production and increased cell proliferation, i.e. fundamental processes of GCs in the ovary. Assuming a similar effect of ACh in vivo, this channel may be a pivotal regulator of physiological GC function linked to actions of the novel intraovarian signaling molecule ACh. (c) 2007 Elsevier Inc. All rights reserved.