The Journal of Physiological Sciences

, Volume 68, Issue 2, pp 153–164 | Cite as

TRPC3 participates in angiotensin II type 1 receptor-dependent stress-induced slow increase in intracellular Ca2+ concentration in mouse cardiomyocytes

  • Yohei Yamaguchi
  • Gentaro IribeEmail author
  • Toshiyuki Kaneko
  • Ken Takahashi
  • Takuro Numaga-Tomita
  • Motohiro Nishida
  • Lutz Birnbaumer
  • Keiji Naruse
Original Paper


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+]i induced 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.


Transient receptor potential canonical 3 Angiotensin II type 1 receptor Ca2+ handling Stretch Cardiomyocyte Mathematical model 



The authors would like to thank Ms. Keiko Kaihara (Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Japan) for her skilled technical support, and Dr. Anastasia Khokhlova (Ural Federal University, Institute of Immunology and Physiology, Russia) for her support in improving the method of myocyte isolation. The authors also thank Ms. Yumiko Morishita (Central Research Laboratory, Okayama University Medical School, Japan) for technical assistance with the histological preparations. This study was funded by the Japan Society for the Promotion of Science (JSPS KAKENHI 23300167, 26282121 and 16K12878 to G.I.), by the Intramural Research Program of the NIH (Project Z01-ES-101864 to L.B.) and by the Life Science Foundation of Japan (as a travel grant to Y.Y.).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

Animal protocols were approved by the Animal Subjects Committee of Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences. All experiments were conducted in accordance with the Guiding Principles for the Care and Use of Animals approved by the Council of the Physiological Society of Japan.

Supplementary material

12576_2016_519_MOESM1_ESM.cellml (142 kb)
ESM1 (CELLML 142 kb)
12576_2016_519_MOESM2_ESM.pdf (348 kb)
ESM2 (PDF 349 kb)


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Copyright information

© The Physiological Society of Japan and Springer Japan 2017

Authors and Affiliations

  • Yohei Yamaguchi
    • 1
  • Gentaro Iribe
    • 1
    Email author
  • Toshiyuki Kaneko
    • 2
  • Ken Takahashi
    • 1
  • Takuro Numaga-Tomita
    • 3
  • Motohiro Nishida
    • 3
  • Lutz Birnbaumer
    • 4
  • Keiji Naruse
    • 1
  1. 1.Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesOkayama UniversityOkayamaJapan
  2. 2.Department of PhysiologyAsahikawa Medical UniversityAsahikawaJapan
  3. 3.Division of Cardiocirculatory Signaling, Okazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences)National Institutes of Natural SciencesOkazakiJapan
  4. 4.Neurobiology LaboratoryNational Institute of Environmental Health ScienceResearch Triangle ParkUSA

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