Piezo1 channels sense whole body physical activity to reset cardiovascular homeostasis and enhance performance

Abstract

Mammalian biology adapts to physical activity but the molecular mechanisms sensing the activity remain enigmatic. Recent studies have revealed how Piezo1 protein senses mechanical force to enable vascular development. Here, we address Piezo1 in adult endothelium, the major control site in physical activity. Mice without endothelial Piezo1 lack obvious phenotype but close inspection reveals a specific effect on endothelium-dependent relaxation in mesenteric resistance artery. Strikingly, the Piezo1 is required for elevated blood pressure during whole body physical activity but not blood pressure during inactivity. Piezo1 is responsible for flow-sensitive non-inactivating non-selective cationic channels which depolarize the membrane potential. As fluid flow increases, depolarization increases to activate voltage-gated Ca2+ channels in the adjacent vascular smooth muscle cells, causing vasoconstriction. Physical performance is compromised in mice which lack endothelial Piezo1 and there is weight loss after sustained activity. The data suggest that Piezo1 channels sense physical activity to advantageously reset vascular control.

Metadata

Item Type:	Article
Authors/Creators:	Rode, B Shi, J Endesh, N Drinkhill, MJ Webster, PJ Lotteau, SJ Bailey, MA Yuldasheva, NY Ludlow, MJ Cubbon, RM Li, J Futers, TS Morley, L Gaunt, HJ Marszalek, K Viswambharan, H Cuthbertson, K Baxter, PD Foster, R Sukumar, P Weightman, A Calaghan, SC Wheatcroft, SB Kearney, MT Beech, DJ
Copyright, Publisher and Additional Information:	© The Author(s) 2017. Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Keywords:	Cardiovascular biology; Membrane biophysics
Dates:	Accepted: 20 June 2017 Published (online): 24 August 2017 Published: 24 August 2017
Institution:	The University of Leeds
Academic Units:	The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Genetics, Health and Therapeutics (LIGHT) > Academic Unit of Cardiovascular Medicine (Leeds)
Depositing User:	Symplectic Publications
Date Deposited:	25 Aug 2017 09:19
Last Modified:	25 Aug 2017 09:19
Status:	Published
Publisher:	Nature Publishing Group
Identification Number:	10.1038/s41467-017-00429-3
Open Archives Initiative ID (OAI ID):	oai:eprints.whiterose.ac.uk:120585

CORE (COnnecting REpositories)

Piezo1 channels sense whole body physical activity to reset cardiovascular homeostasis and enhance performance

Abstract

Metadata

Download

Published Version

Export

Statistics