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Studies on colonic autonomic rhythmicity and its pacemaker mechanism in pathological model animals

Research Project

Project/Area Number 14370189
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionNara Medical University

Principal Investigator

TAKAKI Miyako  Nara Medical University, Physiology II, Professor, 医学部, 教授 (00033358)

Co-Investigator(Kenkyū-buntansha) KADOWAKI Makoto  Nara Medical University], Physiology II, Research Associate, 医学部, 助手 (20305709)
FUKUI Hiroshi  Nara Medical University, Internal medicine III, Professor, 医学部, 教授 (80145838)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥10,500,000 (Direct Cost: ¥10,500,000)
Fiscal Year 2003: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2002: ¥7,400,000 (Direct Cost: ¥7,400,000)
Keywordspacemaker cell / interstitial cells of Cajal / Ca channel / mitochondria / sarcoplasmic reticulum / ryanodine receptor / IP_3 receptor / autonomic rhythmicity
Research Abstract

To clarify the generation mechanisms for autonomic rhythmicity (pacemaker mechanisms) in pathological gut model, pacemaker mechanisms in the normal gut was elucidated by various approaches. (1)The role of pacemaker cells located in the submucosa of the mouse proximal colon. (Submucosal interstitial cells of Cajal : ICC-SM) were investigated by direct recording of pacemaker potentials ICC-SM cells. The result revealed the pacemaker potentials of ICC-SM do not contribute to the generation of peristaltic movements in the longitudinal and circular muscles. (2)To clarify the role of pacemaker potentials of ICC-SM cells, the simultaneous recordings of longitudinal and circular muscle contractions and pacemaker potentials of ICC-SM cells were made. The results suggest that pacemaker potentials drive antiperistaltic movements in the proximal colon to absorb the water from the intraluminal contents to make feces. The pacemaker potentials of ICC-SM is mainly generated and controlled by intracellular calcium handling mechanisms. (3)The results from the mutant mouse genetically deficient of myenteric ICC suggest that several ICC networks localized in the gut wall function as mutual supplementary mechanisms and that enteric nervous system has a crucial role on the compensatory mechanism for deficiency of either ICC network. (4)From mouse embryonic stem (ES) cells, the embryoid body and then cell clusters of gut (ES-gut) were differentiated spontaneously after 3 weeks. Ca oscillation was expressed in ES-guts, and ICC & gap junctions were well differentiated. Such ES guts generate peristalsis-like movements at the frequency of 14 -15 min^<-1>. All results indicated that ICC has an important role on autonomic movements. Possible changes of ICC in inflammatory bowel disease model should be further explored.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (17 results)

All Other

All Publications (17 results)

  • [Publications] Satoshi Yoneda: "Properties of spontaneously active cells distributed in submucosal layer of the mouse proximal colon."J Physiol. 542・3. 887-891 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Satoshi Yoneda: "Effects of nifedipine and nickel ions, inhibitors of voltage-gated Ca-channels, on plateau potentials generated in submucosal interstitial cells of the mouse proximal colon."J Smooth Muscle Res. 39・3. 55-65 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tadao Ishikawa: "Characterization of in vitro gut-like organ formed from mouse embryonic stem cells."Am J Physiol (Cell Physiology). (in press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Satoshi Yoneda: "Pacemaker activity from submucosal interstitial cells of Cajal drives high-frequent and low-amplitude circular muscle contractions in the mouse proximal colon."Neurogastroenterol and Motil. (in press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Miyako Takaki: "Gut Pacemaker Cells : the Interstitial Cells of Cajal (ICC). (J Smooth Muscle Res)"The Japanese Society of Smooth Muscle Research. 24 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Satoshi Yoneda: "Properties of spopntaneously active cells distributed in submucosal layer of the mouse proximal colon"J Physiol. 542-3. 887-897 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Satoshi Yoneda: "Effects of nifedipine and nickel ions, inhibitors of voltage-gated Ca-channels, on plateau potentials generated in submucosal intersititial cells of the mouse proximal colon"J Smooth Muscle Res. 39-3. 55-65 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tadao Ishikawa: "Characterization of in vitro gut-like organ formed from mouse embryonic stem cells"Am J Physiol (Cell Physiology). (in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Satoshi Yoneda: "Pacemaker activity from submucosal interstitial cells of Cajal drives high-frequent and low-amplitude circular muscle contractions in the mouse proximal colon"Neurogastroenterol and Motil. (in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Miyako Takaki: "Gut Pacemaker Cells : the Interstitial Cells of Cajal (ICC)"J Smooth Muscle Res The Japanese Society of Smooth Muscle Research. 24 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Miyako Takaki: "special Reviews : Pacemaker cells in the heart and gut"J Smooth Muscle Res The Japanese Society of Smooth Muscle Research. 1 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Satoshi Yoneda: "Properties of spontaneously active cells distributed in submucosal layer of the mouse proximal"J Physiol. 542・3. 887-897 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Satoshi Yoneda: "Effects of nifedipine and nickel ions, inhibitors of voltage-gated Ca-channels, on plateau"J Smooth Muscle Res. 39・3. 55-65 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tadao Ishikawa: "Characterization of in vitro gut-like organ formed from mouse embryonic stem cells."Am J Physiol (Cell Physiology). in press. (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Miyako Takaki: "J Smooth Muscle Res"The Japanese Society of Smooth Muscle Research. 24 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yoneda S., Takano H., Takaki M., Suzuki H.: "Properties of spontaneously active cells distributed in submucosal layer of the mouse proximal colon"J. Physiol. 542(3). 887-897 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yoneda S., Takano H., Torihashi S., Takaki M., Suzuki H.: "Effects of nifedipine and nickel ions, inhibitors of voltage-gated Ca-channels, on plateau potentials generated in submucosal interstitial cells of the mouse proximal colon"J. Smooth Muscle Res. 39(発表予定). (2003)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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