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

Baptiste Rode, Jian Shi, Naima Endesh, Mark J. Drinkhill, Peter J. Webster, Sabine J. Lotteau, Marc A. Bailey, Nadira Y. Yuldasheva, Melanie J. Ludlow, Richard M. Cubbon, Jing Li, T. Simon Futers, Lara Morley, Hannah J. Gaunt, Katarzyna Marszalek, Hema Viswambharan, Kevin Cuthbertson, Paul D. Baxter, Richard Foster, Piruthivi Sukumar, Andrew Weightman, Sarah C. Calaghan, Stephen B. Wheatcroft, Mark T. Kearney and David J. Beech ()
Additional contact information
Baptiste Rode: University of Leeds
Jian Shi: University of Leeds
Naima Endesh: University of Leeds
Mark J. Drinkhill: University of Leeds
Peter J. Webster: University of Leeds
Sabine J. Lotteau: University of Leeds
Marc A. Bailey: University of Leeds
Nadira Y. Yuldasheva: University of Leeds
Melanie J. Ludlow: University of Leeds
Richard M. Cubbon: University of Leeds
Jing Li: University of Leeds
T. Simon Futers: University of Leeds
Lara Morley: University of Leeds
Hannah J. Gaunt: University of Leeds
Katarzyna Marszalek: University of Leeds
Hema Viswambharan: University of Leeds
Kevin Cuthbertson: University of Leeds
Paul D. Baxter: University of Leeds
Richard Foster: University of Leeds
Piruthivi Sukumar: University of Leeds
Andrew Weightman: University of Manchester
Sarah C. Calaghan: University of Leeds
Stephen B. Wheatcroft: University of Leeds
Mark T. Kearney: University of Leeds
David J. Beech: University of Leeds

Nature Communications, 2017, vol. 8, issue 1, 1-11

Abstract: 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.

Date: 2017
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DOI: 10.1038/s41467-017-00429-3

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