Abstract

Piezo channels are mechanosensitive ion channels. Piezo1 is primarily expressed in nonsensory tissues, whereas Piezo2 is predominantly found in sensory tissues, including dorsal root ganglion (DRG) neurons. However, a recent study demonstrated the intracellular calcium response to Yoda1, a selective Piezo1 agonist, in trigeminal ganglion (TG) neurons. Herein, we investigate the expression of Piezo1 mRNA and protein in mouse and human DRG neurons and the activation of Piezo1 via calcium influx by Yoda1. Yoda1 induces inward currents mainly in small- (<25 μm) and medium-sized (25–35 μm) mouse DRG neurons. The Yoda1-induced Ca2+ response is inhibited by cationic channel blocker, ruthenium red and cationic mechanosensitive channel blocker, GsMTx4. To confirm the specific inhibition of Piezo1, we performed an adeno-associated virus serotype 2/5 (AAV2/5)-mediated delivery of short hairpin RNA (shRNA) into mouse DRG neurons. AAV2/5 transfection downregulates piezo1 mRNA expression and reduces Ca2+ response by Yoda1. Piezo1 also shows physiological functions with transient receptor potential vanilloid 1 (TRPV1) in the same DRG neurons and is regulated by the activation of TRPV1 in mouse DRG sensory neurons. Overall, we found that Piezo1 has physiological functions in DRG neurons and that TRPV1 activation inhibits an inward current induced by Yoda1.

Highlights

  • Chemical and thermal-induced nociceptor responses in sensory neurons have been well studied [1]

  • We tested whether Yoda1 led to a rapid calcium increase through Piezo1 channels in mouse dorsal root ganglion (DRG) neurons

  • It has been reported that the detection of mechanical touch or forces are mediated by different ion channels such as potassium K2P channel, mechanosensitive ion channels (MSCs), TMEM 120A/TACAN, TMEM63/OSCA, TMC1/2, and Piezo1/2 in Drosophila, plants, mice, and humans, respectively [24,25,26,27]

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Summary

Introduction

Chemical and thermal-induced nociceptor responses in sensory neurons have been well studied [1]. Mechanotransduction in sensory neurons is not well understood. Mechanosensitive ion channels (MSCs) represent a critical class of mechanotransduction signals that directly and rapidly convert mechanical force into electrochemical signals [2]. The discriminative molecular identities of mechanotransduction for sensory signals such as touch perception, proprioception, and mechanical pain remained elusive until the discovery of the Piezo channel family, with its members Piezo and Piezo which mediate mechanically activated cationic currents in mammalian cells [3]. Piezo is involved in embryonic vascular maturation, blood pressure regulation, urinary osmoregulation, epithelial homeostasis, neural stem cell fate determination, and axonal guidance, whereas Piezo mediates the sensation of gentle touch, proprioception, tactile allodynia, airway stretch, and lung inflation [4,6,7,8]

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