2002 Fiscal Year Final Research Report Summary
The mechanism of general anesthetics
| Project/Area Number |
13671618
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | Nippon Medical School |
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Principal Investigator |
KITAMURA Akira Nippon Medical School, Department of ANESTHESIOLOGY, Assistant professor, 医学部, 講師 (30291719)
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| Project Period (FY) |
2001 – 2002
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| Keywords | synaptic transmission / patch-clamp / halothane / propofol / GABA |
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| 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.
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