Voltage-Gated Proton Channel HV1 in Microglia
Voltage-Gated Proton Channel HV1 in Microglia
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DOI：
10.1177/1073858413519864
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发表时间：
2014-01
期刊：
影响因子：
--
通讯作者：
Long-Jun Wu
中科院分区：
文献类型：
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作者：
Long-Jun Wu
小胶质细胞是大脑常驻的免疫细胞，它们的功能与正常和患病的大脑有关。小胶质细胞表达大量离子通道，包括 K+ 通道、Na+ 通道、TRP 通道、Cl− 通道和质子通道。这些离子通道在小胶质细胞增殖、迁移以及细胞因子、趋化因子和神经毒性或神经营养物质的产生/释放中发挥着关键作用。在小胶质细胞离子通道中，电压门控质子通道HV1是最近克隆的离子通道，可快速去除去极化细胞质中的质子，并在免疫系统中高表达。然而，人们对小胶质细胞 HV1 在大脑中的功能知之甚少。最近的研究表明，HV1 在小胶质细胞中选择性表达，但在大脑神经元中不表达。在细胞水平上，小胶质细胞 HV1 调节细胞内 pH 值并有助于 NADPH 氧化酶依赖性活性氧的产生。在大脑中动脉闭塞的小鼠模型中，小胶质细胞 HV1 导致神经元细胞死亡和缺血性脑损伤。这篇综述讨论了大脑中小胶质细胞 HV1 质子通道的发现、特性、调节和病理生理学。
Microglia are brain resident immune cells and their functions are implicated in both the normal and diseased brain. Microglia express a plethora of ion channels, including K+ channels, Na+ channels, TRP channels, Cl− channels, and proton channels. These ion channels play critical roles in microglial proliferation, migration, and production/release of cytokines, chemokines, and neurotoxic or neurotrophic substances. Among microglial ion channels, the voltage-gated proton channel HV1 is a recently cloned ion channel that rapidly removes protons from depolarized cytoplasm and is highly expressed in the immune system. However, the function of microglial HV1 in the brain is poorly understood. Recent studies showed that HV1 is selectively expressed in microglia but not neurons in the brain. At the cellular level, microglial HV1 regulates intracellular pH and aids in NADPH oxidase-dependent generation of reactive oxygen species. In a mouse model of middle cerebral artery occlusion, microglial HV1 contributes to neuronal cell death and ischemic brain damage. This review discusses the discovery, properties, regulation, and pathophysiology of microglial HV1 proton channel in the brain.