title: TRPC3 participates in angiotensin II type 1 receptor-dependent stress-induced slow increase in intracellular Ca2+concentration in mouse cardiomyocytes.
abstract: When a cardiac muscle is held in a stretched position, its [Ca2+] transient increases slowly over several minutes in a process known as stress-induced slow increase in intracellular Ca2+concentration ([Ca2+]i) (SSC). Transient receptor potential canonical (TRPC) 3 forms a non-selective cation channel regulated by the angiotensin II type 1 receptor (AT1R). In this study, we investigated the role of TRPC3 in the SSC. Isolated mouse ventricular myocytes were electrically stimulated and subjected to sustained stretch. An AT1R blocker, a phospholipase C inhibitor, and a TRPC3 inhibitor suppressed the SSC. These inhibitors also abolished the observed SSC-like slow increase in [Ca2+]iinduced by angiotensin II, instead of stretch. Furthermore, the SSC was not observed in TRPC3 knockout mice. Simulation and immunohistochemical studies suggest that sarcolemmal TRPC3 is responsible for the SSC. These results indicate that sarcolemmal TRPC3, regulated by AT1R, causes the SSC.
authors.affiliation: Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, 700-8558, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Yamaguchi
authors.affiliation: Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, 700-8558, Japan. iribe@okayama-u.ac.jp.
authors.forename: Gentaro
authors.initials: G
authors.lastname: Iribe
authors.affiliation: Department of Physiology, Asahikawa Medical University, Asahikawa, Hokkaido, 078-8510, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kaneko
authors.affiliation: Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, 700-8558, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Division of Cardiocirculatory Signaling, Okazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences), National Institutes of Natural Sciences, Okazaki, Aichi, 444-8787, Japan.
authors.forename: Takuro
authors.initials: T
authors.lastname: Numaga-Tomita
authors.affiliation: Division of Cardiocirculatory Signaling, Okazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences), National Institutes of Natural Sciences, Okazaki, Aichi, 444-8787, Japan.
authors.forename: Motohiro
authors.initials: M
authors.lastname: Nishida
authors.affiliation: Neurobiology Laboratory, National Institute of Environmental Health Science, Research Triangle Park, NC, 27709, USA.
authors.forename: Lutz
authors.initials: L
authors.lastname: Birnbaumer
authors.affiliation: Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, 700-8558, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Naruse
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D050052:TRPC Cation Channels / Q000378:metabolism*
chemical_list: D044140:Receptor, Angiotensin, Type 1; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; D000804:Angiotensin II; D002118:Calcium
keywords: Angiotensin II type 1 receptor; Ca2+ handling; Cardiomyocyte; Mathematical model; Stretch; Transient receptor potential canonical 3