Peripheral sensory neurons and non-neuronal cells express functional Piezo1 channels

Here, we present evidence showing Piezo1 protein expression in the primary sensory neurons (PSNs) and non-neuronal cells of rat peripheral nervous system. Using a knockdown/knockout validated antibody, we detected Piezo1 immunoreactivity (IR) in similar to 60% of PSNs of rat dorsal root ganglia (DRG) with higher IR density in the small- and medium-sized neurons. Piezo1-IR was clearly identified in DRG perineuronal glia, including satellite glial cells (SGCs) and Schwann cells; in sciatic nerve Schwann cells surrounding the axons and cutaneous afferent endings; and in skin epidermal Merkel cells and melanocytes. Neuronal and non-neuronal Piezo1 channels were functional since various cells (dissociated PSNs and SGCs from DRGs, isolated Schwann cells, and primary human melanocytes) exhibited a robust response to Piezo1 agonist Yoda1 by an increase of intracellular Ca2+ concentration ([Ca2+](i)). These responses were abolished by non-specific Piezo1 antagonist GsMTx4. Immunoblots showed elevated Piezo1 protein in DRG proximal to peripheral nerve injury-induced painful neuropathy, while PSNs and SGCs from rats with neuropathic pain showed greater Yoda1-evoked elevation of [Ca2+](i) and an increased frequency of cells responding to Yoda1, compared to controls. Sciatic nerve application of GsMTx4 alleviated mechanical hypersensitivity induced by Yoda1. Overall, our data show that Piezo1 is widely expressed by the neuronal and non-neuronal cells in the peripheral sensory pathways and that painful nerve injury appeared associated with activation of Piezo1 in PSNs and peripheral glial cells.

Automated summary

In this study, the expression of Piezo1 protein in both primary sensory neurons and non-neuronal cells of the rat peripheral nervous system was observed. It was found that Piezo1 was present in approximately 60% of dorsal root ganglia neurons, with higher levels in small- and medium-sized neurons. Piezo1 was also detected in glial cells surrounding the neurons, Schwann cells, Merkel cells, and melanocytes. Functional Piezo1 channels were observed in various cell types, and the activation of Piezo1 led to an increase in intracellular calcium concentration. Furthermore, nerve injury-induced painful neuropathy was associated with increased Piezo1 expression and activation in sensory neurons and glial cells.