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Osmosensing mechanism of co-operation of Nax and TRPV4 channel

Nax和TRPV4通道合作的渗透传感机制

基本信息

批准号：
18590899
负责人：
SUZUKI Makoto
金额：
$ 2.49万
依托单位：
Jichi Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590899/
关键词：
Ca channel Na channel Osmolality Tonicity Vasopressin Neuronal cell TRPV4 Caチャネル TRPチャネル

项目摘要

TRPV4 was first reported to be a "hypoosmolality-sensing" cation channel. On the following studies with knockout mice(Trpv4^<-/->), we have reported that response of vasopressin to hypertonicity was exaggerated but another group has reported that it was abolished in Trpv4^<-/->. Although controversial in the response, both reports suggest that TRPV4 can be responsive to hypertonic stimuli. To elucidate "hyperosmolality- sensing" in TRPV4 activation, we designed to re-examine the response in vivo and investigate whether TRPV4 was sensitive to hyperosmolality in cultured neuronal cells. Trpv4^<-/->and Trpv4^<+/+> mice were subjected to dehydration from 24 to 96 hrs. Then plasma osmolality and water intake were measured. There was not remarkable difference in plasma osmolality at any period of dehydration but a significant decrease in plasma osmolality of Trpv4^<-/-> at 72 hrs dehydration. Water-crave behavior and amount of water intakes after the dehydrations were not changed. Thus TRPV4 channel may respond to hyperosmolality. Neuronal cell lines with and without TRPV4 and Nax expression were established from the Neuro2a cell line. Hyperosmoliality(400 mOsm)induced robust Ca influx in the TRPV4(+) cells, irrespective of the presence of Nax, while not in the TRPV4(-)cells. The influx was not modified with indomethacin, partially blocked with genistein, miconazole, and completely blunted with pBPB, a blocker of PLA_2. Therefore, TRPV4 is hyperosmolality-sensng channel through activation of PLA_2 in the neuronal cells.

TRPV 4是第一个被报道为“低渗敏感”阳离子通道。在以下对基因敲除小鼠（Trpv 4 ^<-/->）的研究中，我们报道了加压素对高渗的反应被夸大，但另一组报道了它在Trpv 4 ^<-/->中被消除。尽管在反应上存在争议，但两份报告都表明TRPV 4可以对高渗刺激作出反应。为了阐明TRPV 4激活中的“高渗感知”，我们设计重新检查体内反应并研究TRPV 4是否对培养的神经元细胞中的高渗敏感。使Trpv 4 ^<-/->和Trpv 4 ^<+/+>小鼠经历24至96小时的脱水。然后测定血浆渗透压和饮水量。在脱水的任何时期，血浆渗透压均无显著差异，但在脱水72小时时，Trpv 4 ^<-/->的血浆渗透压显著降低。脱水后的渴水行为和饮水量没有改变。因此TRPV 4通道可能对高渗反应。从Neuro 2a细胞系建立具有和不具有TRPV 4和Nax表达的神经元细胞系。高渗（400 mOsm）在TRPV 4（+）细胞中诱导了强烈的Ca内流，而在TRPV 4（-）细胞中则没有。吲哚美辛不改变内流，染料木素、咪康唑可部分阻断内流，PLA_2阻断剂pBPB可完全阻断内流。因此，TRPV 4是通过激活PLA_2而在神经细胞中起高渗敏感作用的通道。