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1993 Fiscal Year Final Research Report Summary

Effect of Na-K exchanger inhibitor bepridil on neuronal death -single fiber study-

Research Project

Project/Area Number 04670487
Research Category

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

Allocation TypeSingle-year Grants
Research Field Neurology
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

KAJI Ryuji  KYOTO UNIVERSITY, Faculty of Medicine Department of Neurology, Lecture, 医学部, 講師 (00214304)

Co-Investigator(Kenkyū-buntansha) NAGAMINE Takashi  Faculty of Medicine Department of Brain Pathophysiology, Assistant, 医学部, 助手 (10231490)
KIMURA Jun  Faculty of Medicine Department of Neurology, Professor, 医学部, 教授 (10204976)
Project Period (FY) 1992 – 1993
Keywordssingle fiber / Na-Ca Exchanger / Na-K pump / K channel / conduction block / blood-nerve barrier / multifocal motor neuropathy / anti-GM1 antibody
Research Abstract

Neuronal death is a consequence of abnormal Ca influx into the cell. This Ca influx is caused by reverse operation of Na-Ca exchanger, which normally excretes calcium in exchange of sodium out of the cell. Recent report suggested a protective effect of Na-K exchanger inhibitors on ischemic neuronal death through preventing the reverse operation (Stys 1991, Ann Neurol 30 : 375). We examined the effect of bepridil, a inhibitor, on the conduction disturbance in a single fiber recording caused by ischemia. Twelve Wistar rats were anesthetized with pentobarbital and had laminectomy over the lower thoracic and lumber spines. After cutting the dura, we made a pool of paraffin over the cauda equina and picked up ventral roots from the tail. A root was hung over a pair of microelectrocles to record a single fiber action potential by stimulating the tail(Figure below). After having made a stable recording, we ligated the proximal end of the root to produce ischemia. Recording were made every minutes, and the procedures were reproduced applying a normal saline or bepridil (0.1 M) over the entire distal stump of the root in order to observe their specific effects. All the 21 fibers treated with saline from 12 rats showed conduction failure by 32 minutes after ligation (mean 22.8(〕SY.+-.〔)4.1). There was however no significant difference between normal saline-treated group and bepridil-treated group (mean 21.1(〕SY.+-.〔)5.2, n=14). The present study did not reveal any beneficial effect of the Na-K exchanger in contrast to the previous reoprt (Stys et al 1991). The difference may be accounted for by two factors. First, ischemic conduction disturbance may be overshadowed by depolarization brought about through suppression of the sodium potassium pump, which normally hyperpolarizes the membrane. Second, bepridil may have other actions than inhibiting the exchanger. Whatever the reason may be, bepridil may not warrant its further clinical trials for ischemic nervous system disorders

  • Research Products

    (13 results)

All Other

All Publications (13 results)

  • [Publications] Kaji R: "Fasciculations evoked by cortical stimulation in amyotrophic lateral sclerosis." Ann Neurol. (in press). (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hamano T: "Lack of prolonged cerebral blood flow change after transcranial magnestic stimulation." Electroenceph Clin Neurophysiol. 89. 207-210 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kaji R: "Pathological findings at the site of conduction block in maltifocal motor neuropathy." Ann Neurol. 33. 152-158 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kaji R: "Amyotrophic lateral sclerosis:what makes the direct cortiospinal tract so vulnerable." Muscle Nerve. 16. 872-874 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kaji R: "Anti-GM1 Antibodies and Impaired Blood-Nerve Barrier May Interfere with Remyelination in Multifocal Motor Neuropathy." Muscle Nerve. 17. 108-110 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hamano T: "Vivration-evoked sensory nerve action potentials derived from Paccinian corpuscles." Electroencephalogr Clin Neurophysiol. 89. 278-286 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kaji R: "Botulinum and Tetanus Neurotoxins." B.R.Das Gupta;Plenum Press,New York, 798 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kaji R,et al.: "Fasciculation evoked by cortical stimulation in amyotrophic lateral sclerosis." Ann Neurol. (in press). (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hamano T,et al.: "Lack of prolonged cerebral blood flow change after transcranial magnestic stimulation." Electroenceph Clin Neurophysiol. 89. 207-210 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kaji R,et al.: "Pathological findings at the site of conduction block in maltifocal motor neuropathy." Ann Neurol. 33. 152-158 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kaji R,et al.: "Amyotrophic lateral sclerosis : what makes the direct cortiospinal tract so vulnerable." Mucle Nerve. 16. 872-874 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kaji R,et al.: "Anti-GM1 Antibodies amd Impaired Blood-Nerve Barrier May Interfer with Remyelination in Multifocal Motor Neuropathy." Muscle Nerve. 17. 108-110 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hamano T,et al.: "Vivration-evoked sensory nerve action potentials derived from Paccinian corpuscles." Electroencephalogr Clin Neurophysiol. 89. 278-286 (1993)

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

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Published: 1995-03-27  

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