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 SukumarAndrew Weightman, Sarah C. Calaghan, Stephen B. Wheatcroft, Mark T. Kearney, David J. Beech

    Research output: Contribution to journalArticlepeer-review

    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.

    Original languageEnglish
    Article number429
    JournalNature Communications
    Volume8
    Issue number1
    Early online date24 Aug 2017
    DOIs
    Publication statusPublished - 2017

    Research Beacons, Institutes and Platforms

    • Manchester Institute for Collaborative Research on Ageing

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