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.
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Communication| Mechanotransduction by Membrane Proteins| April 26 2023
Deciphering mechanically activated ion channels at the single-channel level in dorsal root ganglion neurons
Swetha E. Murthy
(Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Resources, Validation, Visualization, Writing - original draft, Writing - review & editing)
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Swetha E. Murthy Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Resources, Validation, Visualization, Writing - original draft, Writing - review & editing
Disclosures: The author declares no competing interests exist.
This work is part of a special issue on mechanotransduction by membrane proteins.
Received: January 28 2022
Revision Received: March 22 2023
Accepted: April 07 2023
Online ISSN: 1540-7748
Print ISSN: 0022-1295
Silver Family Innovation Fund
© 2023 Murthy
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
J Gen Physiol (2023) 155 (6): e202213099.
January 28 2022
March 22 2023
April 07 2023
Swetha E. Murthy; Deciphering mechanically activated ion channels at the single-channel level in dorsal root ganglion neurons. J Gen Physiol 5 June 2023; 155 (6): e202213099. doi: https://doi.org/10.1085/jgp.202213099
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