| Project/Area Number |
07671889
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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 |
Otorhinolaryngology
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| Research Institution | Kansai Medical University |
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Principal Investigator |
OHNISHI Sumio Kansai Medical University, School of Medicine, assistant, 医学部, 助手 (80257914)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1996: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1995: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | Cochlear outer hair cell / Chloride channel / Potassium channel / Calcium calmodulin-dependent protein kinaseII / Protein phosphatase / N-acetylsphingosine / Calyculin A / 細胞収縮 / 体積減少 / カルシウムイオンチャネル / カリウムイオンチャネル / カルシウム-カルモデュリン / 蛋白脱リン酸化 / カルシウムチャネル / 収縮運動 |
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| Research Abstract |
The intracellular mechanisms of slow shortening in isolated guinea pig cochlear outer hair cells were investigated using inhibitors and/or an activator of protein kinases and protein phosphatases. The slow shortening was induced by tetanic electrical field stimulation.and changes in the cell length volume and intracellular CI^- concentration were microscopically monitored using a chloride-sensitive fluorescent dye. The slow shortening was inhibited by a calmodulin inhibitor. W-7, and a calcium calmodulin-dependent protein kinase II (CaMKII) inhibitor. KN-62. The inhibition by W-7 or KN-62, was abolished by the supplemented conductance of K^+ with valinomycin. Among the protein phosphatase inhibitors tested a type 1 and 2A protein phosphatase inhibitor. calyculin A.inhibited the slow shortening. The inhibition by calyculin A was abolished by the increased CI^- permeability. but neither by the increased K^+ conductance with valinomycin nor by the increased Ca^<2+> conductance with A23187. A protein serine/threonine phosphatase activator, N-acetylsphingosine. inhibited the shortening which was abolished by either valinomycin or a type 2A protein phosphatase inhibitor. okadaic acid but not by calyculin A.These findings suggest the following signaling mechanisms in the slow shortening of outer hair cells : the K^+ channel opening is facilitated through protein phosphorylation by CaMKII and suppressed via okadaic acid-sensitive dephosphorylation, and the C1^- channel opening depends on calyculin A-sensitive protein phosphatase activity.B.V.
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