Remodeling of mitochondrial ATP-sensitive K^+ channels in response to heart failure and atrial fibrillation
| Project/Area Number |
15590719
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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 |
Circulatory organs internal medicine
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| Research Institution | Chiba University |
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Principal Investigator |
SATO Toshiaki Chiba University, Graduate School of Medicine, Associate Professor, 大学院・医学研究院, 助教授 (60244159)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAYA Haruaki Chiba University, Graduate School of Medicine, Professor, 大学院・医学研究院, 教授 (60113594)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2003: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | ATP-sensitive K^+ channel / Mitochondria / Heart failure / Remodeling / Protein kinase C |
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| Research Abstract |
It is well known that the remodeling of ion channels occurs during heart failure and atrial fibrillation. However, the remodeling of ATP-sensitive K^+ channel in inner mitochondrial membrane (mitoK_<ATP> channel) is poorly understood. This study was undertaken to know cardiac mitoK_<ATP> channels are remodeled by heart failure. Single ventricular myocytes were isolated from Bio 14.6 cardiomyopathic hamsters and the mitochondrial flavoprotein oxidation by diazoxide was used to quantify mitoK_<ATP> channel activity. The application of diazoxide elicited oxidation of flavoprotein after a latency of 〜15 min. The latency of the response in Bio 14.6 ventricular myocytes was significantly greater than that in normal F1b hamsters. However, the degree of flavoprotein oxidation in Bio 14.6 cardiomyocytes was comparable to that achieved in F1b cardiomyocytes. These results suggest that the density of mitoK_<ATP> channels seems to be unaltered during heart failure. Opening of mitoK_<ATP> channels has been shown to be potentiated by protein kinase C. We therefore examined if activation of protein kinase C by bradykinin modulates mitoK_<ATP> channel in failing cardiomyocytes. Bradykinin increased mitoK_<ATP> channel activity and abbreviated the latency to mitoK_<ATP> channel opening. These results suggest that the impaired protein kinase C-dependent signal transduction cascade may secondarily modulate the mitoK_<ATP> channel activity in Bio 14.6 cardiomyopathic hamsters.
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Report
(3 results)
Research Products
(40 results)
