Project/Area Number |
10470438
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Surgical dentistry
|
Research Institution | KYUSHU UNIVERSITY |
Principal Investigator |
YOSHIDA Atsuya Dental Hospital, Kyushu University Assist. Prof., 歯学部・附属病院, 講師 (00284521)
|
Co-Investigator(Kenkyū-buntansha) |
ITO Shiniti Faculty of Dentistry. Kyushu University Res. Assist., 歯学部・附属病院, 助手 (00315095)
IKEMOTO Yshimi Faculty of Dentistry. Kyushu University Prof., 歯学部・附属病院, 教授 (90091272)
|
Project Period (FY) |
1998 – 2000
|
Project Status |
Completed (Fiscal Year 2001)
|
Budget Amount *help |
¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 2000: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1999: ¥1,800,000 (Direct Cost: ¥1,800,000)
|
Keywords | Patch-clamp technique / whole cell mode / human recombinant GABA-A receptors / glycine / mIPSCs / nystatine-perforated patch / リコンビナント / ヒトGABA受容体 |
Research Abstract |
We investigate the effects of various anesthetic drugs using patch-clamp technique on human recombinant GABA-A receptors expressed in Sf9 cells. Sf9 cells and expression of human recombinant GABA-A receptors were provided by the second department of Physiology, Faculty of Medicine, Kyushu University until last year, but we can manage all the procedure in our departments this year. We examined the mechanism of the effects of Benzodiazepines on this current. Benzodiazepinees have established efficacy in the treatment of anxiety, insomnia and epilepsy. And it is well known that they produce their pharmacological effects by positively modulating the action of GABA at GABA receptors. But still the detail is remained unclear. In recent Years, Flavone derivatives is reported that its affinity for benzodiaz epine is quite high. Its molecular structure is similar to diazepam. We use several fravone derivatives on human recombinant GABA-A receptors and investigate the effect, but no particular change was occurred. Effects of a volatile anesthetic, isoflurane, on glycinergic miniature inhibitory postsynaptic currents (mIPSCs) were mainly investigated in the mechanically dissociated rat trigeminal nucleus neurons attached with intact glycinergic interneuronal presynaptic nerve terminals. The nystatine-perforated patch recording configuration was used to record the mIPSCs under the voltage-clamp conditions. Isoflurane parallely shifted the glycine concentration-response curve of enzymatically dissociated neurons to the left without changing the maximum response. Isoflurane reversibly increased the frequency of the mIPSCs and prolonged the decay time constant without affecting the mean amplitude. The increase in the frequency of mIPSCs in the presence of isoflurane was also observed in a Ca^<2+>-free external solution.
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