Piezo1 channels play a crucial role in mechanical sensation of dorsal root ganglion neurons innervating hindlimb muscle in rats

Mechanosensitive channels are activated by mechanical stimuli evoked during muscle contraction. Sensory signals are transmitted to the spinal cord through the dorsal root ganglion (DRG), and then significantly contribute to an increase in sympathetic nerve activity and blood pressure (i.e., the skeletal muscle mechanoreflex) during exercise. Piezo2 channels are well established mechanoreceptors expressed in various organs and are highly enriched in sensory neurons, including DRG innervating skeletal muscle. In contrast, considerably less attention has been paid to Piezo1 channels in sensory transduction, largely due to their relatively lower expression (especially in DRG neurons). Consequently, the functional role of Piezo1 channels in muscle-innervating DRG neurons has not been fully elucidated. Purpose: The aim of this investigation was to determine whether Piezo1 channels are functionally expressed in DRG neurons innervating skeletal muscle contributing to mechanosensation. Methods: To label muscle afferent DRG neurons, a fluorescent retrograde tracer (DiI, 60 mg/mL) was injected into the white portion of the gastrocnemius of Sprague–Dawley rats (n=16, body weight: 331±28 g). Five days after the injection, the DRGs were harvested and cultured. Using in vitro whole cell patch clamp recordings from small DRG neurons (0.9999 by Fischer’s exact test]. MA current amplitude was significantly greater in Dil-positive DRG neurons than in the Dil-negative DRG neurons (P< 0.01), while mechanical threshold did not change. Likewise, Yoda-1-induced total charge transfer was significantly greater in Dil-positive DRG neurons than in the Dil-negative DRG neurons (P< 0.05). The presence of IB4 positivity or negativity did not affect the magnitude of MA current, mechanical threshold or Yoda-1-induced total charge transfer. Most importantly, both the number of Yoda-1-positive DRG neurons (Multiple logistic regression, P< 0.01) and Yoda-1-induced total charge transfer (Multiple linear regression; P< 0.05) were found to be significantly associated with the presence of Dil positivity. Moreover, we confirmed that opening of the Piezo1 channel by Yoda-1 sufficiently induced action potentials in muscle afferent DRG neurons. Conclusion: These findings suggest that Piezo1 channels are functionally expressed in DRG neurons innervating skeletal muscle and play an important role in mediating mechanical sensation in rats. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.