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Pathophysiological gignificance of endothelin receptor-mediated regulation of the cardiac ATP-sensitive K channel

Research Project

Project/Area Number 06670099
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field General pharmacology
Research InstitutionChiba University

Principal Investigator

NAKAYA Haruaki  Chiba University, School of Medicine, Professor, 医学部, 教授 (60113594)

Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1995: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1994: ¥1,300,000 (Direct Cost: ¥1,300,000)
KeywordsMyocardial infarction / Endothelin-1 / alpha_1-adreoceptor / K^+ channel opener / Action potential / ATP-sensitive K^+ current / Heart / ATP感受性Kチャネル / Kチャネル開口薬 / ATP感受性K電流
Research Abstract

Recently the number of patients suffering from ischemic heart disease such as angina pectoris and myocardial infarction is increasing in Japan. For the establihsment of the pharmacological strategy, it is important to understand the pathophysiology of ischemic cell damage and ventricular arrhythmias in acute myocardial infarction.
In the ischemic myocytes ATP-sensitive K^+ (K_<ATP>) channels are activated by a decrease in intracellular ATP,resulting in action potential shortening. Activation of K_<ATP> channels may protect ischemic myocardium by indirectly reducing transmembrane Ca^<++> influx. However, K_<ATP> channel opening may lead to occurrence of lethal ventricular arrhythmias due to decreases in action potential duration (APD) and effective refractory period. It has been reported that endogenous endothelin-1 (ET-1) in plasma and sympathetic activity are increased during acute myocardial ischemia. This study was undertaken to examine the effects of ET receptor and alpha_1-adreoceptor stimulation on cardiac K_<ATP> channels by using standard microelectrode and patch clamp techniques. I hoped that by so doing we would gain greater insight into the underlying mechanisms of ischem., cell injuries by these neurohumoral factors than was available from previous studies.
In isolated guinea-pig ventricular cells, stimulation of ET_A receptors and alpha_<1A>-receptors in common inhibited the ATP-sensitive K^+ current (I_<K.ATP>) activated by K^+ channel opener (KCO) , nicorandil or cromakalim. These receptor stimulation also partially reversed the action potential shortening induced by KCO.In addition, alpha_1-adrenergic stimulation inhibited the action potential shortening under an ischemia-simulating condition. Thus, the inhibition of I_<K.ATP> mdiated by ET_A-or alpha_<1A>-receptors may be deleterious for ischemic myocytes because it may produce intracellular Ca^<++> overload.

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] Kobayashi Satoru: "Endothelin-1 partially inhibits ATP-sensitive K^+ current in guinea pig ventricular cells." Journal of Cardiovascular Pharmacology. 27. 12-19 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Takizawa Taichi: "Effects of α_1-agonist on nicorandil-induced outward current in cardiac cells" Heart and Vessels. Supple.9. 38-40 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Nakaya Haruaki: "Recent Progress in Electropharmacology of the Heart" CRC Press, 107-117 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kobayashi Satoru: "Endothelin-1 partially inhibits ATP-sensitive K^+ current in guinea pig ventricular cells" Journal of Cardiovascular Pharmacology. 27. 12-19 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Takizawa Taichi: "Effects of alpha_1-agonist on nicorandil-induced outward current in cardiac cells" Heart and Vessels. Supple. 9. 38-40 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Nakaya Haruaki: "Recent Progress in Electropharmacology of the Heart" CRC Press. 107-117 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kobayashi Satoru: "Endothelin‐1 partially inhibits ATP‐sensitive K^+ current in guinea pig ventricular cells" Journal of Cardiovascular Pharmacology. 27. 12‐19 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Takizawa Taichi: "Effects of α_1‐agonist on nicorandil‐induced outward current in cardiac cells" Heart and Vessels. Supple.9. 38‐40 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Nakaya Haruaki: "Recent Progress in Electropharmacology of the Heart" CRC Press, 107‐117 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Satoru Kobayashi: "Effects of endothelin-1 on ATP-sensitive K^+ currentin cardiac cells" Heart and Vessels. Suppl.9. (1995)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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