2005 Fiscal Year Final Research Report Summary
Trafficking abnormality in genetic arrhythmias and its modulation.
| Project/Area Number |
16590664
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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 | Niigata University |
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Principal Investigator |
AIZAWA Yoshifusa Niigata University, Institute of Medicine and Dentistry, Professor, 医歯学系, 教授 (50143780)
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| Co-Investigator(Kenkyū-buntansha) |
HANAWA Haruo Niigata University, Institute of Medicine and Dentistry, Lecturer, 医歯学系, 講師 (40282983)
CHINUSHI Masaomi Niigata University, Institute of Medicine and Dentistry, Associate Professor, 医歯学系, 助教授 (40303151)
YAMASHITA Fumio Niigata University, Medical and Dental Hospital, Resident, 医歯学総合病院, 医員 (90401752)
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| Project Period (FY) |
2004 – 2005
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| Keywords | genetic arrhythmias / channel protein / electrophysiology / trafficking |
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| Research Abstract |
1. Screening of Genes of myocardial channels and functional assay.
In congenital long QT syndrome, we found abnormal genes coding potassium channel (mainly LQT1) and 5 were de novo. Of these, the amino-acid at the filter site of the pore was found abnormal and loss of function was confirmed. The structure of the membrane domain of LQT1 by a computer showed precisely the abnormal site. New abnormal genes were also found in catecholaminergic polymorphic ventricular tachycardia and reported as the first case from Japan. Totally negative results for gene abnormalities were found in Brugada syndrome, so far.
2. Modulation of trafficking defect.
The C terminal is essential for trafficking of LQT1 and found two cases showing trafficking defect. One is with a case with T578M mutation but the prediction of structural change of the C-terminal of LQT1 by computer analysis was failed. To modulate the trafficking defect, RNA was attempted but mRNA with a single mutation was not suppressed. This led to the re-study of RNAi in mRNA with co-expressed with wild type. Over-expression of K-channel by transfection was possible but, so far, it provided a model of arrhythmia.
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