Roles of TRPC channel activation in the induction of ventricular tachycardias
| Project/Area Number |
21590276
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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 |
General pharmacology
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| Research Institution | Iwate Medical University (2010-2011)
Shinshu University (2009) |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
NAKADA Tsutomu 信州大学, 医学部, 助教 (70452141)
TAKEISHI Yasuchika 福島県立医科大学, 医学部, 教授 (40272067)
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| Project Period (FY) |
2009 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2009: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 心血管 / 血液 / 心不全 / TRPCチャネル / 心室性不整脈 / 早期後脱分極 / SK&F96365 |
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| Research Abstract |
Premature ventricular contraction(PVC) and/or VT were frequently observed in transgenic mice with transient cardiac expression of activated G proteinαq(Gαq-TG ; Model of HF) mice but not in Gαq/DGKζ-TG and wild-type(WT) mice(p<0.01). SK & F96365, a canonical transient receptor potential(TRPC) channel blocker, decreased the number of PVC and prevented VT in anesthetized Gαq-TG mice(p<0.05). 1-oleoyl-2-acyl-sn-glycerol(OAG), a diacylglycerol analogue, increased the number of PVC in isolated Gαq-TG hearts compared with WT hearts and induced VT in Gαq-TG hearts(p<0.01). SK & F96365 decreased the number of PVC and prevented VT in isolated Gαq-TG hearts(p<0.01) even in the presence of OAG. Early afterdepolarization(EAD)-induced triggered activity was frequently observed in single Gαq-TG ventricular myocytes. Moreover, SK & F96365 prevented the EAD-induced triggered activity. These results suggest that TRPC channels participate in VT induction in failing hearts. Chronic nicorandil administration, ATP-sensitive K channel opener, improved heart failure and decreased the number of PVC in Gαq-TG mice. However, it did not improve the increased protein expression levels of TRPC channels 3 and 6.Acute nicorandil administration shortened ventricular monophasic action potential duration in Langendorff-perfused Gαq-TG mouse hearts at age of 32 weeks. These results suggest that the increased protein expression levels of TRPC channels do not necessarily induce VT. Increases in left ventricular end-diastolic pressure(LVEDP) significantly increased the number of PVC in isolated Gαq-TG hearts compared with WT hearts. SK & F96365 decreased the number of PVC in isolated Gαq-TG hearts even in the presence of increased LVEDP. These results suggest that TRPC channels participate in VT induction in failing hearts with the increased LVEDP. This study provides new information regarding the possibility of the development of a new anti-arrhythmic drug.
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Report
(4 results)
Research Products
(13 results)
