title: TRPV2 is critical for the maintenance of cardiac structure and function in mice.
abstract: The heart has a dynamic compensatory mechanism for haemodynamic stress. However, the molecular details of how mechanical forces are transduced in the heart are unclear. Here we show that the transient receptor potential, vanilloid family type 2 (TRPV2) cation channel is critical for the maintenance of cardiac structure and function. Within 4 days of eliminating TRPV2 from hearts of the adult mice, cardiac function declines severely, with disorganization of the intercalated discs that support mechanical coupling with neighbouring myocytes and myocardial conduction defects. After 9 days, cell shortening and Ca(2+) handling by single myocytes are impaired in TRPV2-deficient hearts. TRPV2-deficient neonatal cardiomyocytes form no intercalated discs and show no extracellular Ca(2+)-dependent intracellular Ca(2+) increase and insulin-like growth factor (IGF-1) secretion in response to stretch stimulation. We further demonstrate that IGF-1 receptor/PI3K/Akt pathway signalling is significantly downregulated in TRPV2-deficient hearts, and that IGF-1 administration partially prevents chamber dilation and impairment in cardiac pump function in these hearts. Our results improve our understanding of the molecular processes underlying the maintenance of cardiac structure and function.
authors.affiliation: Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Shikata-cho 2-5-1, Okayama city, Okayama 700-8558, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Katanosaka
authors.affiliation: Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Shikata-cho 2-5-1, Okayama city, Okayama 700-8558, Japan.
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Iwasaki
authors.affiliation: 1] Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Shikata-cho 2-5-1, Okayama city, Okayama 700-8558, Japan [2] Department of Physiology, Kawasaki Medical School, Matsushima 577, Kurashiki, Okayama 701-0192, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ujihara
authors.affiliation: Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Shikata-cho 2-5-1, Okayama city, Okayama 700-8558, Japan.
authors.forename: Satomi
authors.initials: S
authors.lastname: Takatsu
authors.affiliation: Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Shikata-cho 2-5-1, Okayama city, Okayama 700-8558, Japan.
authors.forename: Koki
authors.initials: K
authors.lastname: Nishitsuji
authors.affiliation: Division of Neurology/Molecular Brain Science, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Motoi
authors.initials: M
authors.lastname: Kanagawa
authors.affiliation: Division of Neurology/Molecular Brain Science, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sudo
authors.affiliation: Division of Neurology/Molecular Brain Science, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Toda
authors.affiliation: 1] Department of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8601, Japan [2] College of Life and Health Sciences, Chubu University, Matsumoto-cho 1200, Kasugai, Aichi 487-8501, Japan.
authors.forename: Kimiaki
authors.initials: K
authors.lastname: Katanosaka
authors.affiliation: 1] Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Shikata-cho 2-5-1, Okayama city, Okayama 700-8558, Japan [2] Department of Physiology, Kawasaki Medical School, Matsushima 577, Kurashiki, Okayama 701-0192, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Mohri
authors.affiliation: 1] Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Shikata-cho 2-5-1, Okayama city, Okayama 700-8558, Japan [2] ICORP-SORST-Cell Mechanosensing Project, Japan Science and Technology Agency, Nagoya, Aichi 466-8550, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Naruse
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics* / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006321:Heart; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D051379:Mice; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D050916:TRPV Cation Channels / Q000235:genetics* / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D050916:TRPV Cation Channels; C485717:Trpv2 protein, mouse; D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases; D017526:Receptor, IGF Type 1; D051057:Proto-Oncogene Proteins c-akt; D002118:Calcium