| Project/Area Number |
16591531
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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 | Hirosaki University |
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Principal Investigator |
UENO Shinya Hirosaki University, School of Medicine, Professor, 医学部, 教授 (00312158)
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| Co-Investigator(Kenkyū-buntansha) |
HAYAKARI Makoto Hirosaki University, School of Medicine, Assistant Professor, 医学部, 助教授 (80156421)
MORIYAMA Tomoko Hirosaki University, School of Medicine, Assistant, 医学部, 助手 (90400134)
井上 浩一 浜松医科大学, 医学部, 助手 (80345818)
山田 順子 静岡大学, 大学院・電子科学研究科, 助手 (30334965)
福田 敦夫 浜松医科大学, 医学部, 教授 (50254272)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | neuropathic pain / patch clamp / GABA typeA receptor / P2 receptor / GABAtypeA受容体 / プリン受容体 / 細胞障害 / 異常回路形成 |
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| Research Abstract |
ATP receptors play an important role of establishment of neuropathic pain. Moreove, it has been found that a major inhibitory neurotransmitter, γ-aminobutyric acid (GABA) functions as an excitatory neurotransmitter through ATP receptor activation. Intracellular Cl^- concentration of normal neurons is less than 10 mM, and external Cl concentration in the brain is around 120-130mM. Under these conditions, GABA causes inward flux of Cl^- through GABA typeA channels. In contrast, when intracellular Cl^- concentration increases during development stage of neuros and peripheral nerve injury, GABA cause outward flux of Cl^-. Consequently, GABA relase resulted in neuronal excitation. This change of GABA function is also found in neuropathic pain model. Thus, functions of cloride transporters were investigated, using electorphysilogical approach and yeast two-hybrid system in this period.
The yeast two-hybrid system revealed that neuron-specific K^+-Cl^- cotransporter, KCC2, interacted with brain-type creatine kinase. In addition, using HEK293 cells stablly expressed KCC2, brain-type creatine kinase activated KCC2,resulting in an increase of intracellular Cl^-.
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