An N-terminal variant of Trpv1 channel is required for osmosensory transduction
An N-terminal variant of Trpv1 channel is required for osmosensory transduction
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DOI：
10.1038/nn1614
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发表时间：
2006-01-01
影响因子：
25
通讯作者：
Bourque, CW
中科院分区：
文献类型：
--
作者：
Naeini, RS;Witty, MF;Bourque, CW
体液稳态需要神经垂体释放精氨酸-抗利尿激素（AVP）。这种释放是由下丘脑中特定且高度敏感的“渗透受体”控制的。事实上，视上核（SON）中的avp释放神经元具有直接渗透敏感性，这种渗透敏感性是由拉伸抑制阳离子通道介导的。然而，这些通道的分子性质仍然未知。在这里，我们发现SON神经元表达瞬时受体电位香草样蛋白1 （Trpv1）的n端剪接变体，也被称为辣椒素受体，但不是全长Trpv1。与野生型不同，Trpv1敲除（Trpv1(-/-)）小鼠的SON神经元在高渗刺激下不能产生钌红敏感的膜电导和去极化电位增加。此外，Trpv1（-/-）小鼠在基础条件下表现出明显的血清高渗透压，并且在体内对渗透刺激的AVP反应严重受损。这些结果表明，Trpv1基因可能编码渗透受体的一个核心成分。
Body fluid homeostasis requires the release of arginine-vasopressin (AVP, an antidiuretic hormone) from the neurohypophysis. This release is controlled by specific and highly sensitive 'osmoreceptors' in the hypothalamus. Indeed, AVP-releasing neurons in the supraoptic nucleus (SON) are directly osmosensitive, and this osmosensitivity is mediated by stretch-inhibited cation channels. However, the molecular nature of these channels remains unknown. Here we show that SON neurons express an N-terminal splice variant of the transient receptor potential vanilloid type-1 (Trpv1), also known as the capsaicin receptor, but not full-length Trpv1. Unlike their wild-type counterparts, SON neurons in Trpv1 knockout (Trpv1(-/-)) mice could not generate ruthenium red-sensitive increases in membrane conductance and depolarizing potentials in response to hyperosmotic stimulation. Moreover, Trpv1(-/-) mice showed a pronounced serum hyperosmolality under basal conditions and severely compromised AVP responses to osmotic stimulation in vivo. These results suggest that the Trpv1 gene may encode a central component of the osmoreceptor.