| Project/Area Number |
16590672
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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 | Nagoya University |
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Principal Investigator |
INDEN Yasuya Nagoya University, University Hospital, Assistant Professor, 医学部附属病院, 講師 (10359747)
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| Co-Investigator(Kenkyū-buntansha) |
MUROHARA Toyoaki Nagoya University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (90299503)
KONDO Takahisa Nagoya University, University Hospital, Assistant Professor, 医学部附属病院, 講師 (00303644)
TAKADA Yasunobu Nagoya University, University Hospital, Research Associate, 医学部附属病院, 助手 (80378067)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | pacemaker cell / ionic channel / gene therapy |
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| Research Abstract |
As for the treatment to the bradyarrhythmia, a cardiac pacemaker is generally implanted. And now, the prognosis and QOL of the bradyarrhythmia patient are improving by the artificial pacemaker therapy. However there are some problems in pacemaker therapy. The artificial cardiac pacemaker is very expensive and the battery life is limited. The patients need reoperation for the battery exchange and receive the operative-stress. Therefore as the regeneration medicine to the bradyarrhythmia, making the biological pacemaker cell, which has an automaticity as same as the sinus nodal cell, is tried by the gene introduction. It is because the 4th phase diastolic depolarization happens due to the lack of the inward rectifie K+ channel and the existence of the hyperpolarization-activated inward current channel that the sinus nodal cell has automaticity. This hyperpolarization-activated inward current channel is prescribed by the HCN gene family and it needs the extraction of HCN2 and the HCN4 gene in this HCN gene family to create the pacemaker cell. We evaluated bradyarrhythmia in klotho mutant mice, ageing model. We found that klotho gene expression is essential for the sinoatrial node. We got the HCN4 from the human heart cDNA by the technique of PCR and inserted the HCN4 full length arrangement in the plasmid pcDMA3.1. After the confirmation the full length arrangement of the HCN4-plaemid, we confirmed protein manifestation by Western blot using the human kidney cell. To create the recombinant adenovirus which contained a gotten gene, the HCN4-plaemid was introduced to cosmid-vector pAxCAwtit2. Which means the There is possibility to create the biological pacemaker cell which has automaticity through the diastolic depolarization by introducing the HCN4 gene into the cardiomyocyte using the recombinant adenovirus.
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