1999 Fiscal Year Final Research Report Summary
Generation of transgenic mice with arrythmia expressing a dominant-negative Isk
| Project/Area Number |
10557004
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
General physiology
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| Research Institution | Kobe University |
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Principal Investigator |
TAKUMI Toru Kobe University, School of Medicine, Associate Professor, 医学部, 講師 (00222092)
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| Co-Investigator(Kenkyū-buntansha) |
SHIBANO Toshiro Daiichi Pharmaceutical Co.,Ltd., New Product Research Laboratories II, Senior Researcher, 創薬第二研究所, 主任研究員
MATSUDA Hiroko Kansai Medical University, Professor, 医学部, 教授 (10181736)
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| Project Period (FY) |
1998 – 1999
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| Keywords | Arrythmia / Myocyte / Transgenic mice / K channel |
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| Research Abstract |
To understand physiological function of the Isk channel in heart, we investigated behavior of the Isk channels in three different ways ; in mammalian cultured cells, in isolated ventricular myocytes and in the heart of transgenic mice.
(1)In COS7 cells transfected, Isk was associated with KvLQT1 and HERG. The rapidly activating potassium current was abolished by cotransfection of D77N dominant negative Isk and HERG cDNA.
(2)In isolated ventricular myocytes, two types of outward KィイD2+ィエD2 currents, the rapidly activating potassium channel (which corresponds to IKr) and the slowly activating potassium channels (which corresponds to IKs), are identified. The outward KィイD2+ィエD2 currents were inhibited by the antisense Isk oligonucleotide or D77N dominant negative Isk mutant. The action potential duration in ventricular myocyte was significantly prolonged by introduction of D77N dominant negative mutant.
(3)Transgenic mice expressing a dominant-negative D77N Isk in heart were generated under the control of α-myosin heavy chain promoter. The introduced Isk was strongly expressed in the heart. The electrocardiogram of the mice and electrophysiology using the isolated ventricular myocytes from the mice have been analyzed.
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[Publications] T.Takumi, K.Taguchi, S.Miyake, Y.Sakakida, N.Takashima, C.Matsubara, Y.Maebayashi, K.Okumura, S.Takekida, S.Yamamoto, K.Yagita, L.Yan, M.W.Young and H.Okamura: "A light independent oscillatory gene mPer3 in mouse SCN and OVLT"EMBO J.. 17. 4753-4759 (1998)
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[Publications] T.Takumi, Y.Nagamine, S.Miyake, C.Matsubara, K.Taguchi, S.Takekida, Y.Sakakida, K.Nishikawa, T.Kishimoto, S.Niwa, K.Okumura and H.Okamura: "A mammalian ortholog of Drosophila timeless, highly expressed in SCN and retina, forms a complex with mPER1"Genes Cells. 4. 67-75 (1999)
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