| Project/Area Number |
25670719
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Otorhinolaryngology
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| Research Institution | Kumamoto University |
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Principal Investigator |
Wen-Jie Song 熊本大学, 生命科学研究部, 教授 (90216573)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | KCNQ1/KCNE1 / スフィンゴミエリン / PKD / SMS1 / KCNQ1 / KCNE1 / 血管条 / チャネル |
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| Outline of Final Research Achievements |
We previously showed that sphingomyelin synthase (SMS) deficiency leads to a reduction in expression of the K+ channel KCNQ1 in the inner ear, causing hearing loss. Here, we examined whether manipulation of SMS1 activity affects KCNQ1/KCNE1 currents in single cells. Application of tricyclodecan-9-ylxanthogenate, a nonspecific inhibitor of SMSs, significantly reduced current density and altered channel voltage dependence. Knockdown of SMS1 by a short hairpin RNA, however, reduced current density alone. Consistent with this, overexpression of SMS1 increased the current density without changing channel properties. Furthermore, application of protein kinase D inhibitors also suppressed current density without changing channel properties; this effect was nonadditive with that of SMS1 short hairpin RNA. These results suggest that SMS1 positively regulates KCNQ1/KCNE1 channel density in a protein kinase D-dependent manner.
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