International journal of oral science. 2025 Jun 3;17(1):45. doi: 10.1038/s41368-025-00374-8 Q110.82024

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

牙科初级感觉神经元中Piezo2介导的机械转导的功能和独特作用翻译改进

Pa Reum Lee^{1 2}, Kihwan Lee³, Ji Min Park¹, Shinae Kim¹, Seog Bae Oh^{4 5 6}

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作者单位

¹ Department of Neurobiology and Physiology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, Republic of Korea.

² Brain Science Institute, Korea Institute of Science and Technology, Seoul, Republic of Korea.

³ Tooth-Periodontium Complex Medical Research Center, Seoul National University, Seoul, Republic of Korea.

⁴ Department of Neurobiology and Physiology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, Republic of Korea. odolbae@snu.ac.kr.

⁵ Tooth-Periodontium Complex Medical Research Center, Seoul National University, Seoul, Republic of Korea. odolbae@snu.ac.kr.

⁶ ADA Forsyth Institute, Cambridge, MA, USA. odolbae@snu.ac.kr.

DOI: 10.1038/s41368-025-00374-8 PMID: 40461462

摘要中英对照阅读

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 (Na_V1.8 and Na_V1.9) 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 Na_V1.8 and Na_V1.9, 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.

Piezo2是一种机械敏感性离子通道，在牙源性初级感觉神经元（DPA神经元）中作为关键的机械转导器，可能参与了牙科患者轻度机械刺激过度敏感现象的发生。鉴于Piezo2在不同类型DPA神经元亚群中的广泛表达，本研究旨在表征具有不同电压门控钠通道（VGSCs）和神经肽特征的Piezo2表达型DPA神经元的机械感觉特性。通过全细胞膜片钳记录技术，我们观察到了由机械激活引发的动作电位（AP），并根据去极化阶段是否存在一个峰值将动作电位波形进行分类。单细胞反转录聚合酶链反应结合膜片钳记录揭示了动作电位波形与分子属性之间的特定关联，包括四叠氨钠抗性VGSCs（Na_V1.8和Na_V1.9）以及TRPV1的表达。对DPA神经元转录组数据集的重新分析发现了一些神经肽——包括两种降钙素基因相关肽亚型（α-CGRP和β-CGRP）、P物质和加压素——与Na_V1.8和Na_V1.9表达之间的关联，这些都与定义明确的动作电位亚型有关。使用荧光原位杂交技术在Piezo2⁺DPA神经元中进一步验证了这些分子关联。综上所述，本研究揭示了Piezo2表达DPA神经元的电生理和神经化学异质性及其在特定机械感觉信号传导中的专业化作用。

关键词：Piezo2介导的机械转导; 牙部初级感觉神经元

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