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伸展失活阳离子通道:视上核神经元渗透压敏感性调节的细胞靶点。

Stretch-inactivated cation channels: cellular targets for modulation of osmosensitivity in supraoptic neurons.

作者信息

Bourque Charles W, Voisin Daniel L, Chakfe Yassar

机构信息

Centre for Research in Neuroscience, Montreal General Hospital, McGill University, 1650 Cedar Avenue, Montreal, QC H3G 1A4, Canada.

出版信息

Prog Brain Res. 2002;139:85-94. doi: 10.1016/s0079-6123(02)39009-5.

DOI:10.1016/s0079-6123(02)39009-5
PMID:12436928
Abstract

Rat magnocellular neurosecretory cells (MNCs) show an intrinsic sensitivity to acute changes in fluid osmolality. Experiments in acutely isolated supraoptic MNCs have shown that these responses are due to in part to the cell volume-dependent modulation of gadolinium-sensitive 33 pS stretch-inactivated cation (SIC) channels. Previous studies in vivo have shown that the slope (i.e. gain) of the 'osmosensory' relation between VP release and plasma osmolality can be increased or decreased under various physiological and pathological conditions. Here, we review recent work that shows how changes in external [Na] and excitatory neuropeptides such as angiotensin II (Ang II), cholecystokinin (CCK) and neurotensin (NT), may influence osmosensory gain in acutely isolated MNCs. Whole-cell and single-channel recording experiments have revealed that changes in external Na cause proportional changes in osmosensory gain as a result of modified SIC channel permeability and not by affecting mechanotransduction. In contrast, Ang II, CCK, or NT appear to convergently, and directly, stimulate the osmosensory cation conductance in MNCs. Preliminary analysis in current clamp further suggests that osmosensory gain may be increased upon exposure to these excitatory peptides. Whether such mechanisms contribute to the modulation of osmosensory gain in vivo remains to be established.

摘要

大鼠大细胞神经分泌细胞(MNCs)对体液渗透压的急性变化表现出内在敏感性。对急性分离的视上核MNCs进行的实验表明,这些反应部分归因于细胞体积依赖性调节的钆敏感的33 pS拉伸失活阳离子(SIC)通道。以往的体内研究表明,在各种生理和病理条件下,血管加压素(VP)释放与血浆渗透压之间“渗透压感受”关系的斜率(即增益)可增加或降低。在此,我们综述了最近的研究工作,这些研究表明细胞外[Na]的变化以及诸如血管紧张素II(Ang II)、胆囊收缩素(CCK)和神经降压素(NT)等兴奋性神经肽如何影响急性分离的MNCs中的渗透压感受增益。全细胞和单通道记录实验表明,细胞外Na 的变化会导致渗透压感受增益成比例变化,这是由于SIC通道通透性改变而非影响机械转导所致。相比之下,Ang II、CCK或NT似乎通过共同且直接刺激MNCs中的渗透压感受阳离子电导来发挥作用。电流钳的初步分析进一步表明,暴露于这些兴奋性肽后,渗透压感受增益可能会增加。此类机制是否有助于体内渗透压感受增益的调节仍有待确定。

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