The increased activity of TRPV4 channel in the astrocytes of the adult rat hippocampus after cerebral hypoxia/ischemia.
The increased activity of TRPV4 channel in the astrocytes of the adult rat hippocampus after cerebral hypoxia/ischemia.
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DOI：
10.1371/journal.pone.0039959
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Anderova M
中科院分区：
文献类型：
--
作者：
Butenko O;Dzamba D;Benesova J;Honsa P;Benfenati V;Rusnakova V;Ferroni S;Anderova M
多模态瞬时受体电位香草酸4（TRPV 4）通道是TRP通道家族的成员，是钙可渗透的阳离子通道，其被各种刺激（例如细胞肿胀、低pH和高温）门控。因此，TRPV 4介导的钙内流可能参与与中枢神经系统的各种疾病（如缺血）相关的神经元和神经胶质病理生理学。TRPV 4通道最近在成年大鼠皮层和海马星形胶质细胞中被发现，然而，其在星形胶质细胞病理生理学中的作用仍然没有确定。在本研究中，我们研究了脑缺氧/缺血（H/I）对成年大鼠海马CA 1区星形胶质细胞TRPV 4通道功能表达的影响，采用免疫组织化学分析，膜片钳技术和微荧光细胞内钙成像对星形胶质细胞切片，以及对那些分离自假手术或缺血性海马CA 1区。缺氧/缺血是通过双侧颈总动脉闭塞15分钟结合缺氧条件诱导的。我们的免疫组化分析显示，7天后H/I，TRPV 4的表达显着增强海马星形胶质细胞的CA 1区，增加TRPV 4的表达与星形胶质细胞增生的发展相一致。此外，切片中的成年海马星形胶质细胞或培养的海马星形胶质细胞通过细胞内钙的增加和阳离子电流的激活对TRPV 4激活剂4-α-佛波醇-12，13-二癸酸酯（4αPDD）作出反应，这两者都可通过去除细胞外钙或暴露于TRP拮抗剂（如钌红或RN 1734）而消除。缺氧/缺血损伤后，星形胶质细胞对4αPDD的反应明显增强。总的来说，我们发现TRPV 4通道参与缺血诱导的反应性星形胶质细胞钙离子进入，因此，可能参与缺血性损伤后星形胶质细胞反应性的致病机制。
The polymodal transient receptor potential vanilloid 4 (TRPV4) channel, a member of the TRP channel family, is a calcium-permeable cationic channel that is gated by various stimuli such as cell swelling, low pH and high temperature. Therefore, TRPV4-mediated calcium entry may be involved in neuronal and glia pathophysiology associated with various disorders of the central nervous system, such as ischemia. The TRPV4 channel has been recently found in adult rat cortical and hippocampal astrocytes; however, its role in astrocyte pathophysiology is still not defined. In the present study, we examined the impact of cerebral hypoxia/ischemia (H/I) on the functional expression of astrocytic TRPV4 channels in the adult rat hippocampal CA1 region employing immunohistochemical analyses, the patch-clamp technique and microfluorimetric intracellular calcium imaging on astrocytes in slices as well as on those isolated from sham-operated or ischemic hippocampi. Hypoxia/ischemia was induced by a bilateral 15-minute occlusion of the common carotids combined with hypoxic conditions. Our immunohistochemical analyses revealed that 7 days after H/I, the expression of TRPV4 is markedly enhanced in hippocampal astrocytes of the CA1 region and that the increasing TRPV4 expression coincides with the development of astrogliosis. Additionally, adult hippocampal astrocytes in slices or cultured hippocampal astrocytes respond to the TRPV4 activator 4-alpha-phorbol-12,-13-didecanoate (4αPDD) by an increase in intracellular calcium and the activation of a cationic current, both of which are abolished by the removal of extracellular calcium or exposure to TRP antagonists, such as Ruthenium Red or RN1734. Following hypoxic/ischemic injury, the responses of astrocytes to 4αPDD are significantly augmented. Collectively, we show that TRPV4 channels are involved in ischemia-induced calcium entry in reactive astrocytes and thus, might participate in the pathogenic mechanisms of astroglial reactivity following ischemic insult.
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影响因子：
4.7
作者：
Hill, K;Tigue, NJ;Randall, AD
通讯作者：
Randall, AD
影响因子：
6.3
作者：
Anderova, Miroslava;Vorisek, Ivan;Sykova, Eva
通讯作者：
Sykova, Eva
影响因子：
3.4
作者：
Bai, Ji-Zhong;Lipski, Janusz
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Lipski, Janusz
影响因子：
5.5
作者：
Golovina, VA
通讯作者：
Golovina, VA
影响因子：
16.2
作者：
Agulhon, Cendra;Petravicz, Jeremy;McMullen, Allison B.;Sweger, Elizabeth J.;Minton, Suzanne K.;Taves, Sarah R.;Casper, Kristen B.;Fiacco, Todd A.;McCarthy, Ken D.
通讯作者：
McCarthy, Ken D.