Acid-Sensing Ion Channel 3, But Not Capsaicin Receptor TRPV1, Plays a Protective Role in Isoproterenol-Induced Myocardial Ischemia in Mice
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概要
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Background: Cardiac angina is the hallmark of myocardial ischemia, but the role of the cardiac sensory nerve has received relatively little attention. Recently, both acid-sensing ion channel 3 (ASIC3) and capsaicin receptor (TRPV1) have been suggested as important mediators in sensing cardiac ischemia. However, studies comparing the physiological roles of ASIC3 and TRPV1 in the neuronal-cardiac sensing circuits in vivo are lacking. Methods and Results: Isoproterenol (1.5mg/kg, intraperitoneally) was used to induce transient cardiac ischemia in Asic3+/+ and Asic3-/- mice and a radio-telemetry system was used for electrocardiography with mice in a conscious state. Isoproterenol-induced cardiac ischemia was first demonstrated with ST-segment depression and further confirmed by hypoxia-mediated chemical reactions in cardiac tissue. Mice lacking Asic3 showed prolonged duration of ST-segment depression compared with Asic3+/+ mice (44.3±3.1 vs. 31.7±2.9min; P<0.05). Although ischemia was transient, severe cardiac fibrosis was found in Asic3-/- but not in Asic3+/+ mice littermates. In contrast, isoproterenol-injected Trpv1+/+ and Trpv1-/- mice showed no difference in duration of ST-segment depression and, surprisingly, deletion of Trpv1 did not aggravate cardiac fibrosis. Conclusions: An isoproterenol-induced cardiac ischemia model mimicking clinical conditions of early cardiac angina was used to demonstrate that ASIC3 but not TRPV1 plays a protective role in sensing cardiac ischemia. (Circ J 2011; 75: 174-178)
- 2010-12-25
著者
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Cheng Ching-feng
Institute Of Biomedical Sciences Academia Sinica
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Kuo Terry
Institute of Brain Science, Yang Ming University
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Chen Chih-Cheng
Institute of Biomedical Sciences, Academia Sinica
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Kuo Terry
Institute Of Brain Sciences Yang Ming University
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Cheng Mei-hsin
Institute Of Biomedical Sciences Academia Sinica
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Chen I-lun
Institute Of Biomedical Sciences Academia Sinica
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Lian Wei-shiung
Institute Of Biomedical Sciences Academia Sinica
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Lin Chao-chieh
Institute Of Biomedical Sciences Academia Sinica
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Chen Chih-cheng
Institute Of Biomedical Sciences Academia Sinica
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Kuo Terry
Institute Of Brain Science Yang Ming University
関連論文
- PE-036 Abnormal cardiac autonomic regulation and susceptibility to cardiac ischemia in mice lack of ASIC3(Autonomic nervous system(03)(H),Poster Session(English),The 72nd Annual Scientific Meeting of the Japanese Circulation Society)
- Acid-Sensing Ion Channel 3, But Not Capsaicin Receptor TRPV1, Plays a Protective Role in Isoproterenol-Induced Myocardial Ischemia in Mice
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