Action and mechanism of general anesthtics on subtypes of K channels
| Project/Area Number |
13671575
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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 | KYOTO UNIVERSITY |
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Principal Investigator |
NAMBA Tsunehisa Kyoto Univ., Graduate School of Medicine, Instructor, 医学研究科, 助手 (30283609)
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| Co-Investigator(Kenkyū-buntansha) |
ISHII takahiro Kyoto Univ., Graduate School of Medicine, instructor, 医学研究科, 助手 (40303812)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2001: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Keywords | hyperpolarization-activated / Ca-activated K channel / volatile anesthetics / IK / SK / HCN |
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| Research Abstract |
Action of general anesthetics is not confined to only CNS. They have numerous important actions on many cells including neurons, endothelial cells and-smooth muscle cells. Because K channel is expressed in many cells and has important roles, we believe understanding the action of anesthetics on K channels is essential for the understanding of anesthetic action on whole body. To achieve this goal, we selected Ca-activated K channels (SK and IK) and hyperpolarization-activated channels (HAC)
We tried to construct an ultra rapid drug application system using piezo-driven applicator. This aparatus successfully changes two different solutions in 2 to 3 ms
1) Ca-activated K channels: Using this application system, we have identified that IK, but not SK is inhibited by halothane with time constant of 7 ms in outside-out configuration. From chimeras IK and SK, importance of pore domain for anesthetic inhibition has been suggested. Moreover, in insideout patches, inhibition timeconstant of anesthetic was significantly slower. Therefore we concluded anesthetics act on extracellular side of the pore of IK
2) HAC: We have cloned mammalian clones of HACl and HAC4 and identified that HAC1 and 4 are quite different in activation kinetics. Chimeraic channels between HAC1 and 4 have been constructed to determine the sites important for different activation kinetics. S1, S1-S2 and S6-CNBD are implicated for regulation of the activation
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Report
(3 results)
Research Products
(16 results)
