Skeletal muscle-innervating small dorsal root ganglion neurons exhibit greater mechanosensitivity and responsiveness to Yoda-1 in rats
6 affiliations
- 1Department of Applied Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
- 2Japan Society for the Promotion of Science, Tokyo 102-0083, Japan
- 3College of Life and Health Sciences, Chubu University, Kasugai 487-8501, Japan
- 4Integrated Research Center for Self-Care Technology, National Institute of Advanced Industrial Science and Technology (AIST), Takamatsu, 761-0395, Japan
- 5Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
- 6Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
Abstract
Mechanosensitive channels are activated by mechanical stimuli generated during skeletal muscle contraction. These signals are conveyed to the spinal cord via dorsal root ganglion (DRG) neurons. Piezo2 channels are well-recognized mechanoreceptors expressed in DRG neurons innervating skeletal muscle. In contrast, Piezo1 channels have received far less attention in the context of sensory transduction, largely because their expression levels are relatively low, particularly in DRG neurons. As such, the functional role of Piezo1 channels in skeletal muscle-innervating DRG neurons remains incompletely understood. We therefore determined whether skeletal muscle-innervating DRG neurons exhibit Piezo1-like immunoreactivity and functional responsiveness to the Piezo1 agonist Yoda-1, and whether these neurons display distinct mechanosensitivity. We hypothesized that DRG neurons innervating skeletal muscle would exhibit Piezo1-like immunoreactivity and greater mechanosensitivity and responsiveness to Yoda-1 than unlabeled DRG neurons. Skeletal muscle afferent DRG neurons were identified by injection of a fluorescent retrograde tracer (DiI) into rat hindlimb muscle. Immunofluorescence staining revealed that 24±11% of Piezo1-positive small DRG neurons colocalized with DiI. In vitro whole-cell patch clamp recordings demonstrated a significantly lower mechanical threshold in DiI-positive neurons than in DiI-negative neurons ( P = 0.023). Likewise, Yoda-1 evoked significantly greater total charge transfer in DiI-positive than DiI-negative neurons ( P = 0.014). Importantly, DiI positivity was significantly associated with Yoda-1 responsiveness (odds ratio, 3.72; 95% CI, 1.38–10.05, P = 0.010). Collectively, our results demonstrate that skeletal muscle-innervating DRG neurons exhibit greater mechanosensitivity and responsiveness to Yoda-1, supporting functional Piezo1-related signaling in this sensory neuronal population.
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BibTeX
@article{fukazawa2026skeletal,
title = {{Skeletal muscle-innervating small dorsal root ganglion neurons exhibit greater mechanosensitivity and responsiveness to Yoda-1 in rats}},
author = {Ayumi Fukazawa and Norio Hotta and Amane Hori and Han-Kyul Kim and Gary A. Iwamoto and Scott A. Smith and Wanpen Vongpatanasin and Masaki Mizuno},
journal = {American journal of physiology. Cell physiology},
year = {2026},
month = oct,
doi = {10.1152/ajpcell.90134.2026},
url = {https://doi.org/10.1152/ajpcell.90134.2026},
note = {CC BY},
}
RIS
TY - JOUR
TI - Skeletal muscle-innervating small dorsal root ganglion neurons exhibit greater mechanosensitivity and responsiveness to Yoda-1 in rats
AU - Ayumi Fukazawa
AU - Norio Hotta
AU - Amane Hori
AU - Han-Kyul Kim
AU - Gary A. Iwamoto
AU - Scott A. Smith
AU - Wanpen Vongpatanasin
AU - Masaki Mizuno
PY - 2026
DA - 2026/10/13
JO - American journal of physiology. Cell physiology
DO - 10.1152/ajpcell.90134.2026
UR - https://doi.org/10.1152/ajpcell.90134.2026
AB - Mechanosensitive channels are activated by mechanical stimuli generated during skeletal muscle contraction. These signals are conveyed to the spinal cord via dorsal root ganglion (DRG) neurons. Piezo2 channels are well-recognized mechanoreceptors expressed in DRG neurons innervating skeletal muscle. In contrast, Piezo1 channels have received far less attention in the context of sensory transduction, largely because their expression levels are relatively low, particularly in DRG neurons. As such, the functional role of Piezo1 channels in skeletal muscle-innervating DRG neurons remains incompletely understood. We therefore determined whether skeletal muscle-innervating DRG neurons exhibit Piezo1-like immunoreactivity and functional responsiveness to the Piezo1 agonist Yoda-1, and whether these neurons display distinct mechanosensitivity. We hypothesized that DRG neurons innervating skeletal muscle would exhibit Piezo1-like immunoreactivity and greater mechanosensitivity and responsiveness to Yoda-1 than unlabeled DRG neurons. Skeletal muscle afferent DRG neurons were identified by injection of a fluorescent retrograde tracer (DiI) into rat hindlimb muscle. Immunofluorescence staining revealed that 24±11% of Piezo1-positive small DRG neurons colocalized with DiI. In vitro whole-cell patch clamp recordings demonstrated a significantly lower mechanical threshold in DiI-positive neurons than in DiI-negative neurons ( P = 0.023). Likewise, Yoda-1 evoked significantly greater total charge transfer in DiI-positive than DiI-negative neurons ( P = 0.014). Importantly, DiI positivity was significantly associated with Yoda-1 responsiveness (odds ratio, 3.72; 95% CI, 1.38–10.05, P = 0.010). Collectively, our results demonstrate that skeletal muscle-innervating DRG neurons exhibit greater mechanosensitivity and responsiveness to Yoda-1, supporting functional Piezo1-related signaling in this sensory neuronal population.
SN - 0363-6143
SN - 1522-1563
ER -