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Molecular Mechanisms for Regulation of Renal Ion Channels

Research Project

Project/Area Number 09670059
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General physiology
Research InstitutionIwate Medical University (1998)
Osaka Medical College (1997)

Principal Investigator

KUBOKAWA Manabu  Physiology II,Iwate Medical University Prof., 歯学部, 教授 (70153327)

Co-Investigator(Kenkyū-buntansha) MORI Yoshiaki  Physiology, Osaka Medical College Assist.Prof., 医学部, 講師 (70268192)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1998: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1997: ¥2,000,000 (Direct Cost: ¥2,000,000)
Keywordskidney / proximal tubule / ion transport / K^+ channel / protein kinase A / protein kinase C / cyclic GMP / phosphorylation / 蛋白脱燐酸化 / K^+ channel
Research Abstract

The regulatory mechanism and physiological significance of K^+ channels in the basolateral membrane of proximal tubule cells have been investigated by using the patch-clamp technique. In bullfrog kidneys, inwardly rectifying K^+ channels with the inward conductance of about 50 pS are present in the basolateral membrane of isolated proximal tubule tubule cells. Activity of the K^+ channel is enhanced by intracellular alkalinization, and is inhibited by its acidification in cell-attached patches in the presence of H^+ ionophore, FCCP.The channel is regulated also by intracellular ATP, and plays a major role in formation of the basolateral membrane potential of the proximal tubule cell.
In opossum kidney proximal tubule (OKP) cells, the K^+ channel with inward conductance of about 90 pS was observed, which was also reported to be pH-sensitive and regulated by ATP.Activity of the K^+ channel is inhibited by protein kinase inhibitors, and is enhanced by application of dibutyryl-cAMP or dibutyryl-cGMiP in cell-attached patches. Direct application of cAMP- or cGMP-dependent protein kinase (PKA or PKG) enhanced channel activity in inside-out patches in the presence of ATP (3 mM). In contrast, activity of the K^+ channel is inhibited by direct application of protein kinase C (PKC) in the presence of Ca^<2+> (1muM).These results suggest that the K^+ channel in OKP cells is regulated at least in part by two different phosphorylation processes, PKA or PKG-mediated phosphorylation and PKC-mediated phosphorylation. Moreover, our results suggest that atrial natriuretic peptide is one of the agonist which stimulates PKG-mediated phosphorylation in OKP cells.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] Kubokawa, M., et al: "Modulation of inwardly rectifying ATP-Regulated K^+ channel by phosphorylation process in opossum kidney cells." Japanese Journal of Physiology. 47巻1号. 111-119 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kubokawa, M., et al.: "Dual phosphorylation processes mediate inwardly rectifying K^+ channel in opossum kidney proximal tubule cell." Wiener Klinische Wochenschrift. 109巻12-13号. 509-509 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kubokawa, M., et al.: "Basolateral pH-sensitive K^+ channels mediate membrane potential of proximal tubule cells in bullfrog kidney." Japanese Journal of Physiology. 48巻1号. 1-8 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kubokawa, M., et al.: "Activation of inwardly rectifying K^+ channel in OK proximal tubule cells involves cGMP-dependent phosphorylation process." Japanese Journal of Physiology. 48巻6号. 467-476 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 窪田隆裕、久保川 学: "腎疾患(別冊・医学のあゆみ)" 成清卓二、浅野 泰 編、医歯薬出版, 13-16 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kubokawa, M., Mori, Y., and Kubota, T.: "Modulation of inwardly rectifying ATP-regulated K^+ channel by phosphorylation process in opossum kidney cells." Jpn.J.Physiol.47. 111-119 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kubokawa, M., Mori, Y., and Kubota, T.: "Dual phosphorylation processes mediate inwardly rectifying K^+ channel in opossum kidney proximal tuuble cell." Wein.Klin.Wochenschr.109. 509 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kubokawa, M., Mori, Y., Fujimoto, M., and Kubota, T.: "Basolateral pH-sensitive K^+ channels mediate membrane potential of proximal tubule cells in bullfrog kidney" Jpn.J.Physiol. 48. 1-8 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kubokawa, M., Nakaya, S., Yoshioka Y., Nakamura, K., Sato, F., Mori, Y., and Kubota, T.: "Activation of inwardly recitifying K^+ channel in OK proximal tubule cells by cGMP-dependent phosphorylation process." Jpn.J.Physiol.48. 467-476 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kubota, T.and Kubokawa, M.: Ion Transport in Renal Tubule(in Japanese). In : Renal Disease, Special Issue of Igaku-no-Ayumi, Eds.by Naruse, T.and Asano, Y.Ishiyaku-Shuppan, Tokyo, 13-16 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kubokawa,M.,et al.: "Modulation of inwardly rectifying ATP-regulated K^+ channel by phosphorylation process in opossum kidney cells." Japanese Journal of Physiology. 47巻1号. 111-119 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kubokawa,M.,et al.: "Dual phosphorylation processes mediate inwardly rectifying K^+ channel in opossum kidney proximal tubule cell." Wiener Klinische Wochenschrift. 109巻. 509-509 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kubokawa,M.,et al.: "Basolateral pH-sensitive K^+ channels mediate membrane potential of proximal tubule cells in bullfrog kidney." Japanese Journal of Physiology. 48巻1号. 1-8 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kubokawa,M.,et al.: "Activation of inwardly rectifying K^+ channel in OK proximal tubule cells involves cGMP-dependent phosphorylation process." Japanese Journal of Physiology. 48巻6号. 467-476 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 窪田隆裕、久保川 学: "腎疾患(別冊・医学のあゆみ)" 成清卓二、浅野 泰 編、医歯薬出版, 13-16 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kubokawa,M., et al.: "Modulation of inwardly rectifying ATP-regulated K^+ channel by phosphorylation process in opossum kidney cells." Japanese Journal of Physiology. 47(1). 111-119 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kubokawa,M., et al.: "Dual phosphorylation processes mediate inwardly rectifying K^+ channel in opossum kidney proximal tubule cell." Wiener Klinische Wochenschrift. 109. 509-509 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kubokawa,M., et al.: "Basolateral pH-sensitive K^+ channels mediate membrane potential of proximal tubule cells in bullfrog kidney." Japanese Journal of Physiology. 48(1)(印刷中). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] 窪田隆裕、他: "腎疾患(別冊・医学のあゆみ)" 成清卓二、浅野 泰 編、医歯薬出版, 13-16 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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