Eder C, DeCoursey T E
Institut für Physiologie der Charité, Humboldt Universität, Tucholskystr. 2, D 10117 Berlin, Germany.
Prog Neurobiol. 2001 Jun;64(3):277-305. doi: 10.1016/s0301-0082(00)00062-9.
Microglia, macrophages that reside in the brain, can express at least 12 different ion channels, including voltage-gated proton channels. The properties of H+ currents in microglia are similar to those in other phagocytes. Proton currents are elicited by depolarizing the membrane potential, but activation also depends strongly on both intracellular pH (pH(i)) and extracellular pH (pH(o)). Increasing pH(o) or lowering pH(i) promotes H+ channel opening by shifting the activation threshold to more negative potentials. H+ channels in microglia open only when the pH gradient is outward, so they carry only outward current in the steady state. Time-dependent activation of H+ currents is slow, with a time constant roughly 1 s at room temperature. Microglial H+ currents are inhibited by inorganic polyvalent cations, which reduce H+ current amplitude and shift the voltage dependence of activation to more positive potentials. Cytoskeletal disruptive agents modulate H+ currents in microglia. Cytochalasin D and colchicine decrease the current density and slow the activation of H+ currents. Similar changes of H+ currents, possibly due to cytoskeletal reorganization, occur in microglia during the transformation from ameboid to ramified morphology. Phagocytes, including microglia, undergo a respiratory burst, in which NADPH oxidase releases bactericidal superoxide anions into the phagosome and stoichiometrically releases protons into the cell, tending to depolarize and acidify the cell. H+ currents may help regulate both the membrane potential and pH(i) during the respiratory burst. By compensating for the efflux of electrons and counteracting intracellular acidification, H+ channels help maintain superoxide anion production.
小胶质细胞是存在于大脑中的巨噬细胞，可表达至少12种不同的离子通道，包括电压门控质子通道。小胶质细胞中H⁺电流的特性与其他吞噬细胞中的相似。质子电流是通过使膜电位去极化而引发的，但激活也强烈依赖于细胞内pH值（pH(i)）和细胞外pH值（pH(o)）。提高pH(o)或降低pH(i)会通过将激活阈值转移到更负的电位来促进H⁺通道开放。小胶质细胞中的H⁺通道仅在pH梯度向外时开放，因此它们在稳态下仅携带外向电流。H⁺电流的时间依赖性激活很慢，在室温下时间常数约为1秒。小胶质细胞H⁺电流受到无机多价阳离子的抑制，无机多价阳离子会降低H⁺电流幅度并将激活的电压依赖性转移到更正的电位。细胞骨架破坏剂可调节小胶质细胞中的H⁺电流。细胞松弛素D和秋水仙碱会降低电流密度并减慢H⁺电流的激活。在小胶质细胞从阿米巴样形态转变为分支状形态的过程中，可能由于细胞骨架重组，H⁺电流会发生类似变化。包括小胶质细胞在内的吞噬细胞会经历呼吸爆发，其中NADPH氧化酶将杀菌超氧阴离子释放到吞噬体中，并按化学计量将质子释放到细胞中，趋于使细胞去极化和酸化。H⁺电流可能有助于在呼吸爆发期间调节膜电位和pH(i)。通过补偿电子外流并抵消细胞内酸化，H⁺通道有助于维持超氧阴离子的产生。
