CHANGES IN PROTON CURRENTS IN MURINE MICROGLIA INDUCED BY CYTOSKELETAL DISRUPTIVE AGENTS

Voltage-gated proton currents (I-PR) were investigated in cultured mur ine microglia using the whole-cell configuration of the patch clamp te chnique. At a gradient of 1.5 between intracellular (pH(i) = 6.0) and extracellular pH (pH(o) = 7.5) values, outward I-PR were detected at d epolarizing potentials, while the activation threshold of I-PR was -40 mV. Time-dependent activation of I-PR was fitted by a single exponent ial with a time constant of 661 ms at +40 mV. An increase in the activ ation time constant of I-PR was seen after exposure of microglia to th e cytoskeletal disruptive agents cytochalasin D or colchicine. Moreove r, the current density of I-PR was significantly reduced by 49% in cel ls treated with cytochalasin D and by 27% in cells treated with colchi cine for 24 h. In contrast, voltage-dependence of steady-state activat ion of I-PR was unchanged after disruption of the cytoskeleton. Exposu re of microglia to the cytoskeletal stabilizers phalloidin and taxol d id not affect I-PR Of microglia. (C) 1998 Elsevier Science Ireland Ltd .