Piezo1 Is a Mechanosensor Channel in Central Nervous System Capillaries

Author:

Harraz Osama F.12ORCID,Klug Nicholas R.1ORCID,Senatore Amanda J.1,Hill-Eubanks David C.1,Nelson Mark T.1234

Affiliation:

1. Department of Pharmacology, Larner College of Medicine (O.F.H., N.R.K., A.J.S., D.C.H.-E., M.T.N.), University of Vermont, Burlington.

2. Vermont Center for Cardiovascular and Brain Health (O.F.H., M.T.N.), University of Vermont, Burlington.

3. Division of Cardiovascular Sciences, School of Medical Sciences (M.T.N.), University of Manchester, United Kingdom.

4. Geoffrey Jefferson Brain Research Centre, The Manchester Academic Health Science Centre, Northern Care Alliance NHS Group (M.T.N.), University of Manchester, United Kingdom.

Abstract

Capillaries are equipped to sense neurovascular coupling agents released onto the outer wall of a capillary, translating these external signals into electrical/Ca 2+ changes that play a crucial role in blood flow regulation and ensuring that neuronal demands are met. However, control mechanisms attributable to forces imposed onto the lumen are less clear. Here, we show that Piezo1 channels act as mechanosensors in central nervous system capillaries. Electrophysiological analyses confirmed expression and function of Piezo1 channels in brain cortical and retinal capillaries. Activation of Piezo1 channels evoked currents that were sensitive to endothelial cell–specific Piezo1 deletion. Using genetically encoded Ca 2+ indicator mice and an ex vivo pressurized retina preparation, we found that activation of Piezo1 channels by mechanical forces triggered Ca 2+ signals in capillary endothelial cells. Collectively, these findings indicate that Piezo1 channels are capillary mechanosensors that initiate crucial Ca 2+ signals and could, therefore, have a profound impact on central nervous system blood flow control.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Cardiology and Cardiovascular Medicine,Physiology

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