Functional roles and regulatory mechanisms of voltage-gated proton channels

Voltage-gated proton(H I D1+I D1)channels are unique mechanisms to exclude a massive amount of H I D1+I D 1 from the inside of cells，and are considered to contribute to a rapid regulation of intracellular pH.We studied expression and regulatory mechanisms of the H I D1+i D1 currents in cells with different functions，such as，bone marrow-derived mast cells(BMMC)，rat spinal microglia and murine osteoclasts.Recently high sensitivity to temperature has been found to be a common feature of H I D1+e D1 currents in many types of cells.In both BMMC and microglia，the amplitude of steady-state currents，the activation delay，and the activation rate depended greatly on temperature between22 and 36℃。The half activation voltage was shifted to more negative potentials by heating in both cells.The temperature set-point for the current activation was higher in BMMC possibly due to its intrinsic gating properties or modulatory mechanisms。More than 90%of round/amoeboid microglia expressed H I D…More 1+I D 1 currents。The H I D1+I D1 currents were increased in association with cell swelling induced by intracellular dialysis with acidic pipette solutions(pH5.5-6.8)。The acidosis-induced cell swelling and the accompanying potentiation of the H I D1+ii D1 currents required non-hydrolytic actions of intracellular ATP and were inhibited by agents affecting actin filaments(Phalloidin And Cytochalasin D)，as the hypotonically-activated Cl I D1-I D1 channel in osteoclasts.These findings suggest that cell swelling induced by either intracellular acidification or osmotic imbalance is a crucial signal to increase the H I D1+ii D1 currents of microglia.The swelling-mediated regulation of the H I D1+I D1 channel might operate as a negative feedback mechanism to protect microglia from cytotoxic acidification and swelling in the pathological CNS。These results suggest that activities of the H I D1+i D1 channels are regulated in relation to their functional states and phenotypes and are involved in the various pathophysiolocal effects.Less：Less

Voltage-gated proton (HィイD1+ィエD1) channels are unique mechanisms to exclude a massive amount of HィイD1+ィエD1 from the inside of cells, and are considered to contribute to a rapid regulation of intracellular pH. We studied expression and regulatory mechanisms of the HィイD1+ィエD1 currents in cells with different functions, such as, bone marrow-derived mast cells (BMMC), rat spinal microglia and murine osteoclasts. Recently high sensitivity to temperature has been found to be a common feature of HィイD1+ィエD1 currents in many types of cells. In both BMMC and microglia, the amplitude of steady-state currents, the activation delay, and the activation rate depended greatly on temperature between 22 and 36℃. The half activation voltage was shifted to more negative potentials by heating in both cells. The temperature set-point for the current activation was higher in BMMC possibly due to its intrinsic gating properties or modulatory mechanisms. More than 90% of round/amoeboid microglia expressed HィイD … More 1+ィエD1 currents. The HィイD1+ィエD1 currents were increased in association with cell swelling induced by intracellular dialysis with acidic pipette solutions (pH 5.5-6.8). The acidosis-induced cell swelling and the accompanying potentiation of the HィイD1+ィエD1 currents required non-hydrolytic actions of intracellular ATP and were inhibited by agents affecting actin filaments (phalloidin and cytochalasin D), as the hypotonically-activated ClィイD1-ィエD1 channel in osteoclasts. These findings suggest that cell swelling induced by either intracellular acidification or osmotic imbalance is a crucial signal to increase the HィイD1+ィエD1 currents of microglia. The swelling-mediated regulation of the HィイD1+ィエD1 channel might operate as a negative feedback mechanism to protect microglia from cytotoxic acidification and swelling in the pathological CNS. These results suggest that activities of the HィイD1+ィエD1 channels are regulated in relation to their functional states and phenotypes and are involved in the various pathophysiolocal effects. Less