Deciphering mechanically activated ion channels at the single-channel level in dorsal root ganglion neurons

2023/04/26 by Swetha E. Murthy · 14 citations
Biochemistry, Genetics and Molecular Biology · Chemistry · Medicine · Neuroscience · #Biochemistry #Biology #Biophysics #Channel (broadcasting) #Chemical and Physical Studies #Chemistry #Computer science #Conductance #Dorsal root ganglion #Electrophysiology #Erythrocyte Function and Pathophysiology #Ion channel #Ion channel regulation and function #Membrane potential #Neuroscience #Patch clamp #Physics #Receptor #Sensory system #Somatosensory system #Telecommunications

paper · pdf · doi:10.1085/jgp.202213099

openalex publication_date 2023/04/26 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01

Abstract

Mechanically activated (MA) ion channels confer somatosensory neurons with the ability to sense a wide range of mechanical stimuli. MA ion channel activity in somatosensory neurons is best described by the electrophysiological recordings of MA currents in cultured dorsal root ganglion (DRG) neurons. Biophysical and pharmacological characterization of DRG MA currents has guided the field in screening/confirming channel candidates that induce the currents and facilitate the mechanosensory response. But studies on DRG MA currents have relied mostly on whole-cell macroscopic current properties obtained by membrane indentation, and little is known about the underlying MA ion channels at the single-channel level. Here, by acquiring indentation-induced macroscopic currents as well as stretch-activated single-channel currents from the same cell, we associate macroscopic current properties with single-channel conductance. This analysis reveals the nature of the MA channel responsible for the ensemble response. We observe four different conductances in DRG neurons with no association with a specific type of macroscopic current. Applying this methodology to a Piezo2 expressing DRG neuronal subpopulation allows us to identify PIEZO2-dependent stretch-activated currents and conductance. Moreover, we demonstrate that upon Piezo2 deletion, the remaining macroscopic responses are predominantly mediated by three different single-channel conductances. Collectively, our data predict that at least two other MA ion channels exist in DRG neurons that remain to be discovered.

Cited by

• Mechanisms of PIEZO Channel Inactivation. [europepmc]
• Caldendrin Is a Repressor of PIEZO2 Channels and Touch Sensation in Mice. [europepmc]
• PIEZO ion channels: force sensors of the interoceptive nervous system. [europepmc]
• Neuropeptide Y Y2 Receptors in Sensory Neurons Tonically Suppress Nociception and Itch but Facilitate Postsurgical and Neuropathic Pain Hypersensitivity. [europepmc]
• Neuropeptide Y Y2 receptors in acute and chronic pain and itch. [europepmc]
• PIEZO channels as multimodal mechanotransducers. [europepmc]
• Mechanosensitive Ion Channels: The Unending Riddle of Mechanotransduction. [europepmc]
• Piezo1 and Piezo2 Ion Channels in Neuronal and Astrocytic Responses to MEA Implants in the Rat Somatosensory Cortex. [europepmc]
• Mechanosensitive potassium channels in neurons projecting cardiac axons of the nodose ganglion in rats. [europepmc]
• Targeting Tmem63b and Piezo2 in C-fiber low-threshold mechanoreceptors: Limitation of Vglut3-IRES-Cre. [europepmc]
• The molecular basis of force selectivity by PIEZO2. [europepmc]
• Mechanical regulation of metabolism, epigenetics, and their interplay. [europepmc]
• [Mechanobiology of peripheral nerve development: mechanical properties, sensing, and response]. [europepmc]
• Mechanically-gated currents in mouse sensory neurons lacking PIEZO2 [europepmc]

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