| Project/Area Number |
10670047
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General physiology
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| Research Institution | Osaka City University |
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Principal Investigator |
KUNO Miyuki Osaka City Univ., Dept.of Physiol., Assoc.Prof., 医学部, 助教授 (00145773)
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| Co-Investigator(Kenkyū-buntansha) |
NSAKAMURA Fusao Osaka City Univ., Dept.of Physiol., Research Assoc., 医学部, 助手 (80271196)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1999: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1998: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | proton channels / proton signals / pH regulation / temperature dependency / microglia / mast cells / osteoclasts / cell swelling / アシドーシス / 細胞膨化 / 温度依存性 |
|---|
| Research Abstract |
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
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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
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