このエントリーをはてなブックマークに追加
ID 53904
FullText URL
Author
Iwasaki, Keiichiro
Ujihara, Yoshihiro
Takatsu, Satomi
Nishitsuji, Koki
Kanagawa, Motoi
Sudo, Atsushi
Toda, Tatsushi
Katanosaka, Kimiaki
Mohri, Satoshi
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 Ca2+ 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.
Note
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
Published Date
2014-05-29
Publication Title
Nature Communications
Volume
volume5
Publisher
Nature Publishing Group
Start Page
3932
ISSN
2041-1723
NCID
AA12645905
Content Type
Journal Article
Official Url
http://dx.doi.org/10.1038/ncomms4932
Related Url
http://ousar.lib.okayama-u.ac.jp/metadata/53904
language
英語
Copyright Holders
© 2014 Macmillan Publishers Limited. All rights reserved. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
File Version
publisher
Refereed
True
DOI
PubMed ID
Web of Science KeyUT