TRPV2 is critical for the maintenance of cardiac structure and function in mice

Yuki Katanosaka, Keiichiro Iwasaki, Yoshihiro Ujihara, Satomi Takatsu, Koki Nishitsuji, Motoi Kanagawa, Atsushi Sudo, Tatsushi Toda, Kimiaki Katanosaka, Satoshi Mohri, Keiji Naruse

Research output: Contribution to journalArticle

56 Citations (Scopus)

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 Ca2+ -dependent intracellular Ca2+ 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.

Original languageEnglish
Article number3932
JournalNature Communications
Volume5
DOIs
Publication statusPublished - May 29 2014

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TRPV Cation Channels
maintenance
mice
Maintenance
muscle cells
Insulin-Like Growth Factor I
Muscle Cells
IGF Type 1 Receptor
insulin
secretions
hemodynamics
impairment
Hemodynamics
Somatomedins
Phosphatidylinositol 3-Kinases
stimulation
Cardiac Myocytes
Cations
Dilatation
Down-Regulation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)
  • Medicine(all)

Cite this

TRPV2 is critical for the maintenance of cardiac structure and function in mice. / Katanosaka, Yuki; Iwasaki, Keiichiro; Ujihara, Yoshihiro; Takatsu, Satomi; Nishitsuji, Koki; Kanagawa, Motoi; Sudo, Atsushi; Toda, Tatsushi; Katanosaka, Kimiaki; Mohri, Satoshi; Naruse, Keiji.

In: Nature Communications, Vol. 5, 3932, 29.05.2014.

Research output: Contribution to journalArticle

Katanosaka, Y, Iwasaki, K, Ujihara, Y, Takatsu, S, Nishitsuji, K, Kanagawa, M, Sudo, A, Toda, T, Katanosaka, K, Mohri, S & Naruse, K 2014, 'TRPV2 is critical for the maintenance of cardiac structure and function in mice', Nature Communications, vol. 5, 3932. https://doi.org/10.1038/ncomms4932
Katanosaka, Yuki ; Iwasaki, Keiichiro ; Ujihara, Yoshihiro ; Takatsu, Satomi ; Nishitsuji, Koki ; Kanagawa, Motoi ; Sudo, Atsushi ; Toda, Tatsushi ; Katanosaka, Kimiaki ; Mohri, Satoshi ; Naruse, Keiji. / TRPV2 is critical for the maintenance of cardiac structure and function in mice. In: Nature Communications. 2014 ; Vol. 5.
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