Microglial cells interact with all components of the central nervous system (CNS) and are increasingly recognized to play essential roles during brain development, homeostasis and disease pathologies. Functions of microglia include maintaining tissue integrity, clearing cellular debris and dead neurons through the process of phagocytosis, and providing tissue repair by releasing anti-inflammatory cytokines and neurotrophic factors. Changes of microglial ionic homeostasis (Na⁺, Ca²⁺, K⁺, H⁺, Cl⁻) are important for microglial activation, including proliferation, migration, cytokine release and reactive oxygen species production, etc. These are mediated by ion channels and ion transporters in microglial cells. Here, we review the current knowledge about the role of major microglial ion channels and transporters, including several types of Ca²⁺ channels (store-operated Ca²⁺ entry (SOCE) channels, transient receptor potential (TRP) channels and voltage-gated Ca²⁺ channels (VGCCs)) and Na⁺ channels (voltage-gated Na⁺ channels (Nav) and acid-sensing ion channels (ASICs)), K⁺ channels (inward rectifier K⁺ channels (K_ir), voltage-gated K⁺ channels (K_V) and calcium-activated K⁺ channels (K_Ca)), proton channels (voltage-gated proton channel (Hv1)), and Cl⁻ channels (volume (or swelling)-regulated Cl⁻ channels (VRCCs) and chloride intracellular channels (CLICs)). In addition, ion transporter proteins such as Na⁺/Ca²⁺ exchanger (NCX), Na⁺-K⁺-Cl^- cotransporter (NKCC1), and Na⁺/H⁺ exchanger (NHE1) are also involved in microglial function in physiology and brain diseases. We discussed microglial activation and neuroinflammation in relation to the ion channel/transporter stimulation under brain disease conditions and therapeutic aspects of targeting microglial ion channels/transporters for neurodegenerative disease, ischemic stroke, traumatic brain injury and neuropathic pain.

小胶质细胞与中枢神经系统 (CNS) 的所有组成部分相互作用，并且越来越被认为在大脑发育、体内平衡和疾病病理过程中发挥重要作用。小胶质细胞的功能包括维持组织完整性，通过吞噬作用清除细胞碎片和死亡神经元，并通过释放抗炎细胞因子和神经营养因子来提供组织修复。小胶质细胞离子稳态的变化（Na ⁺、Ca ²⁺、K ⁺、H ⁺、Cl ^-) 对小胶质细胞的激活很重要，包括增殖、迁移、细胞因子释放和活性氧的产生等。这些是由小胶质细胞中的离子通道和离子转运蛋白介导的。在这里，我们回顾了目前关于主要小胶质细胞离子通道和转运蛋白的作用的知识，包括几种类型的 Ca ²⁺通道（存储操作的 Ca ²⁺进入（SOCE）通道、瞬时受体电位（TRP）通道和电压门控通道）。 Ca ²⁺通道 (VGCC)) 和 Na ⁺通道（电压门控 Na ⁺通道 (Nav) 和酸敏感离子通道 (ASIC)）、K ⁺通道（内向整流器 K ⁺通道（K _ir)、电压门控 K ⁺通道 (K _V ) 和钙激活的 K ⁺通道 (K _Ca ))、质子通道（电压门控质子通道 (Hv1)）和 Cl ^-通道（体积（或膨胀）调节）Cl ^-通道（VRCC）和氯细胞内通道（CLIC））。此外，离子转运蛋白如 Na ⁺ /Ca ²⁺交换器 (NCX)、Na ⁺ -K ⁺ -Cl ^-协同转运蛋白 (NKCC1) 和 Na ⁺ /H ⁺交换器 (NHE1) 也参与生理学和脑部疾病中的小胶质细胞功能。我们讨论了与脑疾病条件下的离子通道/转运蛋白刺激相关的小胶质细胞激活和神经炎症，以及针对神经退行性疾病、缺血性中风、创伤性脑损伤和神经性疼痛的靶向小胶质细胞离子通道/转运蛋白的治疗方面。