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Science. 2018 Oct 26;362(6413):464-467. doi: 10.1126/science.aau6324.

PIEZOs mediate neuronal sensing of blood pressure and the baroreceptor reflex.

Author information

1
Howard Hughes Medical Institute, Neuroscience Department, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
2
Howard Hughes Medical Institute, Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
3
Abboud Cardiovascular Research Center, Department of Internal Medicine and Molecular Physiology and Biophysics, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
4
Veterans Affairs Medical Center, Iowa City, IA 52242, USA.
5
Howard Hughes Medical Institute, Neuroscience Department, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA 92037, USA. ardem@scripps.edu.

Abstract

Activation of stretch-sensitive baroreceptor neurons exerts acute control over heart rate and blood pressure. Although this homeostatic baroreflex has been described for more than 80 years, the molecular identity of baroreceptor mechanosensitivity remains unknown. We discovered that mechanically activated ion channels PIEZO1 and PIEZO2 are together required for baroreception. Genetic ablation of both Piezo1 and Piezo2 in the nodose and petrosal sensory ganglia of mice abolished drug-induced baroreflex and aortic depressor nerve activity. Awake, behaving animals that lack Piezos had labile hypertension and increased blood pressure variability, consistent with phenotypes in baroreceptor-denervated animals and humans with baroreflex failure. Optogenetic activation of Piezo2-positive sensory afferents was sufficient to initiate baroreflex in mice. These findings suggest that PIEZO1 and PIEZO2 are the long-sought baroreceptor mechanosensors critical for acute blood pressure control.

PMID:
30361375
DOI:
10.1126/science.aau6324

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