Functional and distinct roles of Piezo2-mediated mechanotransduction in dental primary afferent neurons

Abstract Piezo2, a mechanosensitive ion channel, serves as a crucial mechanotransducer in dental primary afferent (DPA) neurons and is potentially involved in hypersensitivity to mild mechanical irritations observed in dental patients. Given Piezo2’s widespread expression across diverse subpopulatio...

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Main Authors: Pa Reum Lee, Kihwan Lee, Ji Min Park, Shinae Kim, Seog Bae Oh
Format: Article
Language:English
Published: Nature Publishing Group 2025-06-01
Series:International Journal of Oral Science
Online Access:https://doi.org/10.1038/s41368-025-00374-8
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author Pa Reum Lee
Kihwan Lee
Ji Min Park
Shinae Kim
Seog Bae Oh
author_facet Pa Reum Lee
Kihwan Lee
Ji Min Park
Shinae Kim
Seog Bae Oh
author_sort Pa Reum Lee
collection DOAJ
description Abstract Piezo2, a mechanosensitive ion channel, serves as a crucial mechanotransducer in dental primary afferent (DPA) neurons and is potentially involved in hypersensitivity to mild mechanical irritations observed in dental patients. Given Piezo2’s widespread expression across diverse subpopulations of DPA neurons, this study aimed to characterize the mechanosensory properties of Piezo2-expressing DPA neurons with a focus on distinct features of voltage-gated sodium channels (VGSCs) and neuropeptide profiles. Using whole-cell patch-clamp recordings, we observed mechanically activated action potentials (APs) and classified AP waveforms based on the presence or absence of a hump during the repolarization phase. Single-cell reverse transcription polymerase chain reaction combined with patch-clamp recordings revealed specific associations between AP waveforms and molecular properties, including tetrodotoxin-resistant VGSCs (NaV1.8 and NaV1.9) and TRPV1 expression. Reanalysis of the transcriptomic dataset of DPA neurons identified correlations between neuropeptides—including two CGRP isoforms (α-CGRP and β-CGRP), Substance P, and Galanin—and the expression of NaV1.8 and NaV1.9, which were linked to defined AP subtypes. These molecular associations were further validated in Piezo2+ DPA neurons using fluorescence in situ hybridization. Together, these findings highlight the electrophysiological and neurochemical heterogeneity of Piezo2-expressing DPA neurons and their specialized roles in distinct mechanosensory signal transmission.
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spelling doaj-art-e91bffaf53764cd79ac60f3d3ec182892025-08-20T03:25:12ZengNature Publishing GroupInternational Journal of Oral Science2049-31692025-06-0117111410.1038/s41368-025-00374-8Functional and distinct roles of Piezo2-mediated mechanotransduction in dental primary afferent neuronsPa Reum Lee0Kihwan Lee1Ji Min Park2Shinae Kim3Seog Bae Oh4Department of Neurobiology and Physiology, School of Dentistry and Dental Research Institute, Seoul National UniversityTooth-Periodontium Complex Medical Research Center, Seoul National UniversityDepartment of Neurobiology and Physiology, School of Dentistry and Dental Research Institute, Seoul National UniversityDepartment of Neurobiology and Physiology, School of Dentistry and Dental Research Institute, Seoul National UniversityDepartment of Neurobiology and Physiology, School of Dentistry and Dental Research Institute, Seoul National UniversityAbstract Piezo2, a mechanosensitive ion channel, serves as a crucial mechanotransducer in dental primary afferent (DPA) neurons and is potentially involved in hypersensitivity to mild mechanical irritations observed in dental patients. Given Piezo2’s widespread expression across diverse subpopulations of DPA neurons, this study aimed to characterize the mechanosensory properties of Piezo2-expressing DPA neurons with a focus on distinct features of voltage-gated sodium channels (VGSCs) and neuropeptide profiles. Using whole-cell patch-clamp recordings, we observed mechanically activated action potentials (APs) and classified AP waveforms based on the presence or absence of a hump during the repolarization phase. Single-cell reverse transcription polymerase chain reaction combined with patch-clamp recordings revealed specific associations between AP waveforms and molecular properties, including tetrodotoxin-resistant VGSCs (NaV1.8 and NaV1.9) and TRPV1 expression. Reanalysis of the transcriptomic dataset of DPA neurons identified correlations between neuropeptides—including two CGRP isoforms (α-CGRP and β-CGRP), Substance P, and Galanin—and the expression of NaV1.8 and NaV1.9, which were linked to defined AP subtypes. These molecular associations were further validated in Piezo2+ DPA neurons using fluorescence in situ hybridization. Together, these findings highlight the electrophysiological and neurochemical heterogeneity of Piezo2-expressing DPA neurons and their specialized roles in distinct mechanosensory signal transmission.https://doi.org/10.1038/s41368-025-00374-8
spellingShingle Pa Reum Lee
Kihwan Lee
Ji Min Park
Shinae Kim
Seog Bae Oh
Functional and distinct roles of Piezo2-mediated mechanotransduction in dental primary afferent neurons
International Journal of Oral Science
title Functional and distinct roles of Piezo2-mediated mechanotransduction in dental primary afferent neurons
title_full Functional and distinct roles of Piezo2-mediated mechanotransduction in dental primary afferent neurons
title_fullStr Functional and distinct roles of Piezo2-mediated mechanotransduction in dental primary afferent neurons
title_full_unstemmed Functional and distinct roles of Piezo2-mediated mechanotransduction in dental primary afferent neurons
title_short Functional and distinct roles of Piezo2-mediated mechanotransduction in dental primary afferent neurons
title_sort functional and distinct roles of piezo2 mediated mechanotransduction in dental primary afferent neurons
url https://doi.org/10.1038/s41368-025-00374-8
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