| Project/Area Number |
15591651
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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 | University of Yamanashi (2005)
Yokohama City University (2003-2004) |
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Principal Investigator |
ANDOH Tomio UNIVERSITY OF YAMANASHI, DEPARTMENT OF RESEARCH INTERDISCIPLINARY GRADUATE SCHOOL OF MEDICINE AND ENGINEERING, PROFESSOR, 大学院・医学工学総合研究部, 教授 (00193110)
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| Co-Investigator(Kenkyū-buntansha) |
ECHIGO Noriyuki YOKOHAMA CITY UNIVERSITY SCHOOL OF MEDICINE, RESEARCH ASSOCIATE, 医学部, 助手 (00363797)
原田 高志 横浜市立大学, 医学部附属病院, 助手 (40326038)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2005: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2004: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2003: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Keywords | ATP sensitive K channel / neuron / substantia nigra / adenosine / ischemia-reperfusion / mitochondria / oxygen radical / 黒質ドーパミンニューロン / protein kinase C / フラビン蛋白 |
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| Research Abstract |
ATP-sensitive K (K_<ATP>) channels are widely expressed in cytoplasmic membranes of neurons and couple cell metabolism to excitability. They are considered to play important roles in controlling seizure activity during hypoxia and in neuroprotection against cell damage during hypoxia, ischemia and excitotoxicity by hyperpolarizing neurons and reducing excitability. It is known that adenosine augments opening of cardiac surface K_<ATP> by reducing sensitivity of these channels to ATP blockade. We investigated if similar modulation works in neuronal channels. Whole cell voltage-clamp recordings were made using rat midbrain slices to record the membrane current and conductance in principal neurons of substantia nigra pars compacta (SNc).
When a pipette solution contained 1mM ATP and an external solution contained 25mM glucose, the membrane current at -60mV and cellular conductance remained stable for at least 15min. When slices were treated with (-)-N^6-2-phenylisopropyl adenosine (R-PIA), a selective agonist for A1 adenosine receptors, the outward current with the amplitude of 109.9±26.6pA developed slowly for 15 to 20min in the same condition and conductance increased to 229±50% of the baseline. These changes were strongly inhibited by 200μM tolbutamide, suggesting that opening of K_<ATP> channels mediated these changes. Pretreatment with 8-cyclopentyltheophylline (CPT), a selective A1 adenosine receptor antagonist, abolished the outward current and conductance increases. These results suggest that activation of A1 adenosine receptor promotes opening of K_<ATP> channels in principal neurons of SNc by removing blockade with ATP.
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