title: Abnormal cardiac autonomic regulation in mice lacking ASIC3.
abstract: Integration of sympathetic and parasympathetic outflow is essential in maintaining normal cardiac autonomic function. Recent studies demonstrate that acid-sensing ion channel 3 (ASIC3) is a sensitive acid sensor for cardiac ischemia and prolonged mild acidification can open ASIC3 and evoke a sustained inward current that fires action potentials in cardiac sensory neurons. However, the physiological role of ASIC3 in cardiac autonomic regulation is not known. In this study, we elucidate the role of ASIC3 in cardiac autonomic function using Asic3(-/-) mice. Asic3(-/-) mice showed normal baseline heart rate and lower blood pressure as compared with their wild-type littermates. Heart rate variability analyses revealed imbalanced autonomic regulation, with decreased sympathetic function. Furthermore, Asic3(-/-) mice demonstrated a blunted response to isoproterenol-induced cardiac tachycardia and prolonged duration to recover to baseline heart rate. Moreover, quantitative RT-PCR analysis of gene expression in sensory ganglia and heart revealed that no gene compensation for muscarinic acetylcholines receptors and beta-adrenalin receptors were found in Asic3(-/-) mice. In summary, we unraveled an important role of ASIC3 in regulating cardiac autonomic function, whereby loss of ASIC3 alters the normal physiological response to ischemic stimuli, which reveals new implications for therapy in autonomic nervous system-related cardiovascular diseases.
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, 128 Academia Road, Section 2, Taipei 115, Taiwan ; Department of Medical Research, Tzu Chi General Hospital and Department of Pediatrics, Tzu Chi University, Hualien 970, Taiwan.
authors.forename: Ching-Feng
authors.initials: CF
authors.lastname: Cheng
authors.affiliation: Institute of Brain Science, Yang Ming University, Taipei 112, Taiwan.
authors.forename: Terry B J
authors.initials: TB
authors.lastname: Kuo
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, 128 Academia Road, Section 2, Taipei 115, Taiwan.
authors.forename: Wei-Nan
authors.initials: WN
authors.lastname: Chen
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, 128 Academia Road, Section 2, Taipei 115, Taiwan.
authors.forename: Chao-Chieh
authors.identifier: 0000-0001-5890-9004
authors.initials: CC
authors.lastname: Lin
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, 128 Academia Road, Section 2, Taipei 115, Taiwan ; Taiwan Mouse Clinic-National Comprehensive Mouse Phenotyping and Drug Testing Center, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Chih-Cheng
authors.identifier: 0000-0003-4768-5660
authors.initials: CC
authors.lastname: Chen
mesh_terms: D062565:Acid Sensing Ion Channels / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000235:genetics; D006339:Heart Rate / Q000235:genetics; D006801:Humans; D007545:Isoproterenol / Q000633:toxicity; D051379:Mice; D008822:Mice, Transgenic; D017202:Myocardial Ischemia / Q000235:genetics* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D011984:Sensory Receptor Cells / Q000378:metabolism* / Q000473:pathology; D013610:Tachycardia / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology
chemical_list: C508378:ASIC3 protein, mouse; D062565:Acid Sensing Ion Channels; D007545:Isoproterenol