Proton signaling mediated by voltagegated proton channels
由电压门控质子通道介导的质子信号传导
基本信息
- 批准号:14570045
- 负责人:
- 金额:$ 2.18万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (C)
- 财政年份:2002
- 资助国家:日本
- 起止时间:2002 至 2003
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
We have investigated how the voltage-gated proton (H^+) channels regulate H^+ signaling in osteoclasts, microglia and bone-marrow-derived mast cells (BMMC). The Q_<10> value was > 2.0 for conductance and 3 -6 for gating parameters. These high Q_<10> values were preserved well in both microglia and BMMC, which differed in the expression rate of the channel, implying that the high temperature dependence resides in the channel itself. The Q_<10> value for the conductance was, however, often decreased at high temperature or in swollen cells, thus, indicating that the activation status of the H^+ channel is heterogeneous. To clarify actions of the H^+ channel in intact cells, the channel activity in response to various types of cell acidosis was examined in the perforated-whole cell recordings under intrinsic pH buffers. In osteoclasts, an activator for protein kinase C, PMA, induced cell acidosis and activation of the H^+ channel. The reversal potential was served as a real-time monitor for changes in cellular pH in clamped cells. In microglia, the H^+ channel was activated accompanying either acute or prolonged cell acidosis. The channel activation terminated upon removal of the acidosis due to the H^+ extrusion. A part of the activation was, however, modified by ΔpH-independent processes. In addition, sometimes increases in intracellular Ca^<2+> or flux of CL^-, a counter ion for H^+, were associated with the acidosis. Thus H^+ signaling is intimately related to synergistic actions of other ion signals. This study has provided evidences that the H^+ can maintain cellular pH homeostasis by sensing minor changes in pH disturbances and, simultaneously, would trigger H^+ to the surrounding cells.
我们研究了电压门控质子(H^+)通道如何调节破骨细胞、小胶质细胞和骨髓源性肥大细胞(BMMC)中的H^+信号。Q_<;10>;值为电导为>;2.0,门控参数为3-6。这些高Q值在小胶质细胞和BMMC中都保存得很好,这两种细胞的通道表达速率不同,这意味着高温依赖存在于通道本身。然而,在高温或肿胀的细胞中,电导的Q_10>;值往往降低,从而表明H^+通道的激活状态是不均匀的。为了阐明H~+通道在完整细胞中的作用,在固有的pH缓冲液中,在穿孔全细胞记录中检测了不同类型细胞酸化时的通道活性。在破骨细胞中,蛋白激酶C的激活剂PMA诱导细胞酸化和H^+通道的激活。反转电位被用作钳制细胞中细胞pH变化的实时监测。在小胶质细胞中,H^+通道被激活,并伴有急性或长期的细胞酸中毒。由于H^+的挤出,当酸中毒消除时,通道激活终止。然而,部分激活被Δ不依赖于pH的过程修饰。此外,有时细胞内Ca~(2+)和Gt~(2+)或H~(2+)的拮抗剂CL~(-)流量的增加与酸中毒有关。因此,H^+信号与其他离子信号的协同作用密切相关。这项研究提供了证据,表明H~(++)可以通过感知pH扰动的微小变化来维持细胞的pH动态平衡,同时也会触发H~(++)到周围细胞。
项目成果
期刊论文数量(58)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
森泰生, 稲垣千代子, 久野みゆき, 井上隆司, 岡田泰伸, 今泉祐治: "薬理学のQOLへの貢献2:細胞増殖・分化・死を制御するイオンメカニズムと創薬"Folia Pharmacol.Jpn.. 122. 201-214 (2003)
Yasuo Mori、Chiyoko Inagaki、Miyuki Kuno、Takashi Inoue、Yasunobu Okada、Yuji Imaizumi:“药理学对 QOL 2 的贡献:控制细胞增殖、分化和死亡的离子机制和药物发现” Folia Pharmacol.Jpn.. 122 .201 -214 (2003)
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Morihata, H., Mori, H., Sakai, H., Kawawaki, J., sawada, M., Tsutada, T., Kuno, M.: "Activation of voltage-gated proton channels and calcium mobilization upon acute and prolonged cell acidosis in rat micorogilia"Biophys.J.. 86. 129a (2004)
Morihata, H.、Mori, H.、Sakai, H.、Kawawaki, J.、sawada, M.、Tsutada, T.、Kuno, M.:“电压门控质子通道的激活和急性和长时间的钙动员
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Shimakawa, S., Suzuki, S., Miyamoto, R., Takitani, K., Tanaka, K., Tanabe, T., Wakamiya, E., Nakamura, F., Kuno, M., Matsuura, S., Watanabe, Y., Tamai, H.: "Neuropilin-2 is overexpresed in the rat brain after limbic seizures."Brain Res.. 956. 67-73 (2002)
岛川,S.,铃木,S.,宫本,R.,泷谷,K.,田中,K.,田边,T.,若宫,E.,中村,F.,久野,M.,松浦,S.,
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Mori, H., Sakai, H., Morihata, H., Yamano, T., Kuno, M.: "A voltage-gated H^+ channel is a powerful mechanism for pH homeostasis in murine steoclasts"Kobe J Med Sci. 48. 87-96 (2002)
Mori, H.、Sakai, H.、Morihata, H.、Yamano, T.、Kuno, M.:“电压门控 H^ 通道是小鼠破骨细胞 pH 稳态的强大机制”Kobe J Med Sci。
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Kuno, M., Morihata, H., Mori H., Kawawaki, J.: "Effects of temperature on the voltage-gated proton channels and proton signaling"Jpn.J.Physiol.. Vol.52,Suppl.. S117 (2002)
Kuno, M.、Morihata, H.、Mori H.、Kawawaki, J.:“温度对电压门控质子通道和质子信号传导的影响”Jpn.J.Physiol.. Vol.52,Suppl.. S117(
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KUNO Miyuki其他文献
KUNO Miyuki的其他文献
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{{ truncateString('KUNO Miyuki', 18)}}的其他基金
Functions of vacuolar H+-ATPases and voltage-gated proton channels coexisted in the plasma membrane of osteoclasts
破骨细胞质膜中液泡H-ATP酶和电压门控质子通道的功能共存
- 批准号:
23390043 - 财政年份:2011
- 资助金额:
$ 2.18万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Temperature-sensitive recruitment of voltage-gated proton channels
电压门控质子通道的温度敏感募集
- 批准号:
20590213 - 财政年份:2008
- 资助金额:
$ 2.18万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Roles of proton channels in proton signaling : pH-clamp and analysis of proton current oscillation
质子通道在质子信号传导中的作用:pH钳和质子电流振荡分析
- 批准号:
16590168 - 财政年份:2004
- 资助金额:
$ 2.18万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Regulatory mechanisms of activity and expression of voltage-gated proton channels
电压门控质子通道的活性和表达的调节机制
- 批准号:
12670045 - 财政年份:2000
- 资助金额:
$ 2.18万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Functional roles and regulatory mechanisms of voltage-gated proton channels
电压门控质子通道的功能作用和调节机制
- 批准号:
10670047 - 财政年份:1998
- 资助金额:
$ 2.18万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Ion channels and the regulatory mechanisms in different phenotypic mast cells derived from bone marrow hematopoietic stem cells
骨髓造血干细胞不同表型肥大细胞的离子通道及调控机制
- 批准号:
05670052 - 财政年份:1993
- 资助金额:
$ 2.18万 - 项目类别:
Grant-in-Aid for General Scientific Research (C)
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