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1998 Fiscal Year Final Research Report Summary

Novel physiological function of cardiac beta-adrenoceptor-dependent chloride channel

Research Project

Project/Area Number 09670047
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General physiology
Research InstitutionSaga Medical School

Principal Investigator

EHARA Tsuguhisa  Saga Medical School, Fac.of Med., Prof., 医学部, 教授 (50037446)

Co-Investigator(Kenkyū-buntansha) SHIOYA Takao  Saga Medical School, Fac.of Med., Assist., 医学部, 助手 (20253594)
Project Period (FY) 1997 – 1998
Keywordschloride channel / CFTR / RVD / cardiac cell / guinea-pig / cell-volume regulation / cell-swelling
Research Abstract

1. C1 channels in ventricular cells
Experiments were performed to investigate whether guinea-pig ventricular cells possess the swelling-activated chloride channels (I_C_1, _s_w_e_l_l). The results showed that, in these preparations, I_C_1, _s_w_e_l_l was consistently activated by hypotonic challenges.
2. Role of CFTR C1 current in volume regulation in cardiac cells
A new reliable method was developed to monitor the changes in cell volume. The microscopic cell images taken by a CCD camera were continuously processed by a high-speed computer to calculate the area of cell contour, which reflected the cell volume. With this method, the following results were obtained. When cells were exposed to hypotonic solutions, there was a definite cell-swelling, and activation of CFTR current by adrenaline produced a decrease of cell volume in the osmotically inflated cells (RVD). The activation of CFTR current was found to play a role in the cell-volume regulation even under isotonic conditions. In isotonic solutions with external 5 to 10 Mm K, activation of CFTR tended to decrease the cell volume, whereas at 40 to 140 mM K it increased the cell volume depending on the K concentration which determined the cell membrane potential. These effects of CFTR current were inhibited by removal of external C1 ions, C1 channel blockers, and acetylcholine. These findings indicate that CFTR current, in association with the flow of transmembrane K currents, can regulate the volume of cardiac cells under isotonic conditions. It can also be inferred that CFTR current may regulate the content of intracellular solutes in cardiac cells under various physiological and pathophysiological conditions.
Thus, it has been clarified that two types of C1 current play an important role in the regulation of cell volume in cardiac cells.

  • Research Products

    (8 results)

All Other

All Publications (8 results)

  • [Publications] K.Hirahara: "Intracellular Mg^<2+> depletion depresses the delayed rectifier K^+ current in guinea-pig ventricular myocytes." Jpn.J.Physiol.48(1). 81-89 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Ishihara: "A repolarization-induced transient increase in the outward current of the inward rectifier K^+ channel in guinea-pig cardiac myocytes." J.Physiol.510(3). 755-771 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Matsubayashi: "On the mechanism of the enhancement of delayed rectifier K^+ current by extracellular ATP in guinea-pig ventricular myocytes." Pfliigers Arch.-Eur.J.Physiol.(in press). (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Matsubayashi, T.et al.: "On the mechanism of the enhancement of delayed rectifire K^+ current by extracellular ATP in guinea-pig ventricular myocytes." Pflugers Arch.(in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ishihara, K.et al.: "A repolarization-induced transient increase in the outward current of the inward rectifier K^+ current in guinea-pig cardiac myocytes." J.Physiol.510. 755-771 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hirahara, K.et al.: "Intracellular Mg^<2+> depletion depresses the delayed rectifier K^+ current in guinea pig ventricular myocytes." Jpn.J.Physiol.48. 81-89 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sakaguchi, M.et al.: "The swelling-induced Cl^- current in guinea-pig atrial myocytes : Inhibition by glibenclamide." J.Physiol.505. 41-52 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Matsuura, H.et al.: "Selective enhancement of the slow componet of delayed rectifier K^+ current in guinea-pig atrial cells by external ATP." J.Physiol.503. 45-54 (1997)

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

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Published: 1999-12-08  

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