Kv3.3 channels harboring a mutation of spinocerebellar ataxia type 13 alter excitability and induce cell death in cultured cerebellar neurons
| Project/Area Number |
24790230
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
General physiology
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| Research Institution | National Institute of Health Sciences |
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Principal Investigator |
IRIE Tomohiko 国立医薬品食品衛生研究所, 薬理部, 主任研究官 (20546551)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Keywords | 小脳 / 小脳失調症 / プルキンエ細胞 / イオンチャネル |
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| Research Abstract |
The cerebellum plays crucial roles in controlling sensorimotor functions, and patients of spinocerebellar ataxia type 13 exhibit cerebellar atrophy and cerebellar symptoms. The disease is an autosomal dominant disorder and caused by missense mutations in the voltage-gated K+ channels Kv3.3 expressed intensely in the cerebellar Purkinje cells, the sole output neurons from the cerebellar cortex. We examined how these mutations caused the cerebellar disease by lentiviral expression of the mutant Kv3.3 in mouse cultured Purkinje cells. Mutant Kv3.3 suppressed outward currents, broadened action potentials, and elevated basal intracellular calcium concentration in Purkinje cells.The mutant-expressing Purkinje cells showed impaired dendrites, which were significantly rescued by blockade of P/Q-type Ca2+ channels. These results suggest that Purkinje cells in the patients also exhibit similar abnormalities, which may account for the pathology of the disease.
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Report
(3 results)
Research Products
(15 results)
