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The mechanism of general anesthetics

Research Project

Project/Area Number 13671618
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Anesthesiology/Resuscitation studies
Research InstitutionNippon Medical School

Principal Investigator

KITAMURA Akira  Nippon Medical School, Department of ANESTHESIOLOGY, Assistant professor, 医学部, 講師 (30291719)

Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥2,000,000 (Direct Cost: ¥2,000,000)
Keywordssynaptic transmission / patch-clamp / halothane / propofol / GABA / シングルチャネルレコーディング / カルシウムイオンチャンネル / NMDA / AMPA
Research Abstract

We studied the mechanism of action of general anesthetics on transmitter release and postsynaptic responses in both excitatory and inhibitory systems. Spontaneous miniature inhibitory and excitatory postsynaptic currents (mIPSCs and mEPSCs) were recorded with whole-cell and cell-atached patch-clamp techniques in rat cortical neurons established synaptic networks. The application of 0.6 mM halothane or 0.3μM propofol prolonged the duration of mIPSCs and enhanced the total charge during each spontaneous synaptic event. Halothane also decreased the frequency of mIPSC and miniature non-NMDA EPSCs. Experiments using specific high voltage-gated calcium channel blockers indicated that halothane blocked N-type and P/Q type calcium channels without effect on L-type calcium channels, thus leading to a decrease in the release of both excitatory and inhibitory neurotransmitters. Cell-attached patch-clamp recordings revealed no differences in single-channel conductance by application of each drug. Analysis of patch open probability revealed 4- to 5-fold increase in the open probability of channels on each drug, and indicated that halothane increased it with increasing the mean open life time, meanwhile propofol did with decreasing the interburst interval. The observed differences between halothane and propofol may be reflected in different clinical effects and usage.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (8 results)

All Other

All Publications (8 results)

  • [Publications] 北村晶他: "ラット皮質ニューロンにおける抑制性シナプス伝達へのハロセンおよびプロポフォールの作用への考察"麻酔と蘇生. 37. 69-70 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 佐藤良一, 北村晶: "重症心不全患者より得たヒト心筋細胞におけるKATPチャネルへのニコラジルの薬理効果"Therapeutic Research. 22. 685-687 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kitamura A, et al.: "Effects of Halothane and Propofol on Excitatory and Inhibitory Synaptic Transmission in Rat Cortical Neurons"The Journal of Pharmacology and Experimental Therapeutics. 304. 162-171 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kitamura A, et al.: "Halothane and Propofol Modulation of GABA_A Receptor-Mediated Inhibitory Postsynaptic Currents"Anesthesia and Resuscitation. 37. 69-70 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sato R, Kitamura A, et al.: "The effect of Nicorandil on K_<ATP> Channel in human cardiomyocyte"The rapentic Research. 22(4). 685-687 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kitamura A, et al.: "Effects of Halothene and Propofol on Excitatory and Inhibitory Synaptic Transmissino in Rat Cortical Neurons"The Journal of Pharmacology and Experimental Tharapeutics. 304. 162-171 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kitamura A.: "Effects of halothane and propofol on excitatory and inhibitory synaptic transmission in rat cortical neurons"The Journal of Pharmacology and Experimental Therapeutics. 304・1. 162-171 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 北村 晶: "ラット皮質ニューロンにおける抑制性シナプス伝達へのハロセン、プロポフォールの作用への考察"麻酔と蘇生. 37・3. 69-70 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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