Voltage-gated proton channels in microglia

Microglia. macrophages that reside in the brain, can express at least 12 di fferent ion channels. including voltage-gated proton channels. The properti es of H+ currents in microglia are similar to those in other phagocytes. Pr oton currents are elicited by depolarizing the membrane potential, but acti vation also depends strongly on both intracellular pH (pH(i)) and extracell ular pH (pH(o)). Increasing pH(o) or lowering pH(i) promotes H+ channel ope ning by shifting the activation threshold to more negative potentials. H+ c hannels in microglia open only when the pH gradient is outward, so they car ry 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. M icroglial 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+ cur rents in microglia. Cytochalasin D and colchicine decrease the current dens ity 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 bac tericidal superoxide anions into the phagosome and stoichiometrically relea ses protons into the cell, tending to depolarize and acidify the cell. H+ c urrents may help regulate both the membrane potential and pH(i) during the respiratory burst. By compensating for the efflux of electrons and countera cting intracellular acidification, H+ channels help maintain superoxide ani on production. (C) 2001 Elsevier Science Ltd. All rights reserved.