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2003 Fiscal Year Final Research Report Summary

Proton signaling mediated by voltagegated proton channels

Research Project

Project/Area Number 14570045
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General physiology
Research InstitutionOsaka City University

Principal Investigator

KUNO Miyuki  Osaka City University, Graduate School of Medicine, Department of Physiology, Associate Professor, 大学院・医学研究科, 助教授 (00145773)

Project Period (FY) 2002 – 2003
Keywordsproton channel / temperature dependence / osteoclast / cell swelling / pH regulation / proton sensor / phorbol ester / microglia
Research Abstract

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.

  • Research Products

    (17 results)

All Other

All Publications (17 results)

  • [Publications] Sakuta, K., Morihata, H., Mori, H., Sakai, H., Kuno, M.: "Cell swelling as an intermediate signal leading to activation of a Cl^- channel in extracellular calcium-sensing of murine osteoclasts."Osaka City Med.J.. 48. 29-38 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sakuta, K., Sakai, H., Mori, H., Morihata, H., Kuno, M.: "Na^+-dependence of extracellular calcium-sensing mechanisms leading to activation of an outwardly rectifying Cl^- channel in murine osteoclasts."Bone. 31. 374-380 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 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)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Mori, H., Sakai, H., Morihata, H., Yamano, T., Kuno, M.: "A voltage-gated H^+ channel is a powerful mechanism for pH homeostasis in murine osteoclasts."Kobe J.Med.Sci.. 48. 87-96 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 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)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Mori, H., Sakai, H., Morihata, H., Kawawaki, J., Amano, H., Yamano, T., Kuno, M.: "Regulatory mechanisms and physiological relevance of a voltage-gated H^+ channel in murine osteoclasts : phorbol myristate acetate induced cell acidosis and the channnel activation."J.Bone Miner.Res.. 18. 2069-2076 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sakuta, K., Morihata, H., Mori, H., Sakai, H., Kuno, M.: "Cell swelling as an intermediate signal leading to activation of a Cl^-channel in extracellular calcium-sensing of murine osteoclasts"Osaka City Med J.. 48. 29-38 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sakuta, K., Sakai, H., Mori, H., Morihata, H., Kuno, M.: "Na^+-dependence of extracellular calcium-sensing mechanisms leading to activation of an outwardly rectifying Cl^-channel in murine osteoclasts"Bone. 31. 374-380 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] 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 overexpressed in the rat brain after limbic seizures"Brain Res. 956. 67-73 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] 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)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yasuo, M., Inagaki, c., Kuno, M., Inoue, T., Okada, Y., Imaizumi, Y.: "Yakurigaku no QOL eno kouken 2: Saibou Zoushoku・bunka・shi o seigyosuru ion mechanism to souyaku"Folia Pharmacol.Jpn.. 122. 201-214 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Mori, H., Sakai, H., Morihata, H., Kawawaki, J., Amano, H., Yamano, T., Kuno, M.: "Regulatory mechanisms and physiological relevance of a voltage-gated H^+ channel in murine osteoclasts : Phorbol myristate acetate induces cell acidosis and the channel activation"J.Bone Miner.Res.. 18. 2069-2076 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sakai, H., Mori H., Morihata, H., Kawawaki, J., Shioi, A., Kuno, M.: "(Abstract form) Effect of membrane potential on acid-secretion via proton-translocating subunit (c) of a vacuolar type H^+-ATPase from murine osteoclasts"J.bone Miner.Res.. 17(Supple 1). S255 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] 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)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Morihata, H., Tsutada, T., Kawawaki, J., Mori, H., Miki, T., Kuno, M.: "Elevation of intracellular Ca^<2+> induced by external acidosis in microglia"Neurosci.Res.. Suppl 26. S105 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kuno, M.: "Ion signaling of osteoclasts in bone remodeling"Jpn.J.Physiol.. 53,Suppl.. S54 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] 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)

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      「研究成果報告書概要(欧文)」より

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Published: 2005-04-19  

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