Prager-Khoutorsky M, Bourque C W
Centre for Research in Neuroscience, Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, Quebec, Canada.
J Neuroendocrinol. 2015 Jun;27(6):507-15. doi: 10.1111/jne.12270.
Rat magnocellular neurosecretory cells (MNCs) release vasopressin and oxytocin to promote antidiuresis and natriuresis at the kidney. The osmotic control of oxytocin and vasopressin release at the neurohypophysis is required for osmoregulation in these animals, and this release is mediated by a modulation of the action potential firing rate by the MNCs. Under basal (isotonic) conditions, MNCs fire action potentials at a slow rate, and this activity is inhibited by hypo-osmotic conditions and enhanced by hypertonicity. The effects of changes in osmolality on MNCs are mediated by a number of different factors, including the involvement of synaptic inputs, the release of taurine by local glial cells and regulation of ion channels expressed within the neurosecretory neurones themselves. We review recent findings that have clarified our understanding of how osmotic stimuli modulate the activity of nonselective cation channels in MNCs. Previous studies have shown that osmotically-evoked changes in membrane potential and action potential firing rate in acutely isolated MNCs are provoked mainly by a modulation of nonselective cation channels. Notably, the excitation of isolated MNCs during hypertonicity is mediated by the activation of a capsaicin-insensitive cation channel that MNCs express as an N-terminal variant of the transient receptor potential vanilloid 1 (Trpv1) channel. The activation of this channel during hypertonicity is a mechanical process associated with cell shrinking. The effectiveness of this mechanical process depends on the presence of a thin layer of actin filaments (F-actin) beneath the plasma membrane, as well as a densely interweaved network of microtubules (MTs) occupying the bulk of the cytoplasm of MNCs. Although the mechanism by which F-actin contributes to Trpv1 activation remains unknown, recent data have shown that MTs interact with Trpv1 channels via binding sites on the C-terminus, and that the force mediated through this complex is required for channel gating during osmosensory transduction. Indeed, displacement of this interaction prevents channel activation during shrinking, whereas increasing the density of these interaction sites potentiates shrinking-induced activation of Trpv1. Therefore, the gain of the osmosensory transduction process can be regulated bi-directionally through changes in the organisation of F-actin and MTs.
大鼠大细胞神经分泌细胞（MNCs）释放血管加压素和催产素，以促进肾脏的抗利尿和利钠作用。神经垂体中催产素和血管加压素释放的渗透调节对于这些动物的渗透压调节是必需的，并且这种释放是由MNCs对动作电位发放频率的调节介导的。在基础（等渗）条件下，MNCs以缓慢的速率发放动作电位，这种活动在低渗条件下受到抑制，而在高渗状态下增强。渗透压变化对MNCs的影响是由许多不同因素介导的，包括突触输入的参与、局部神经胶质细胞释放牛磺酸以及神经分泌神经元自身表达的离子通道的调节。我们综述了最近的研究发现，这些发现阐明了我们对渗透刺激如何调节MNCs中非选择性阳离子通道活性的理解。先前的研究表明，急性分离的MNCs中膜电位和动作电位发放频率的渗透诱发变化主要是由非选择性阳离子通道的调节引起的。值得注意的是，高渗状态下分离的MNCs的兴奋是由一种辣椒素不敏感的阳离子通道的激活介导的，MNCs将其表达为瞬时受体电位香草酸受体1（Trpv1）通道的N端变体。高渗状态下该通道的激活是一个与细胞收缩相关的机械过程。这个机械过程的有效性取决于质膜下方一层薄薄的肌动蛋白丝（F-肌动蛋白）的存在，以及占据MNCs细胞质大部分的密集交织的微管（MTs）网络。虽然F-肌动蛋白促进Trpv1激活的机制仍然未知，但最近的数据表明，MTs通过C端的结合位点与Trpv1通道相互作用，并且在渗透感觉转导过程中，通过这种复合物介导的力是通道门控所必需的。事实上，这种相互作用的位移会阻止收缩过程中的通道激活，而增加这些相互作用位点的密度会增强收缩诱导的Trpv1激活。因此，渗透感觉转导过程的增益可以通过F-肌动蛋白和MTs组织的变化进行双向调节。
