The Piezo2 ion channel is mechanically activated by low-threshold positive pressure

Kyung Chul Shin,In Hwa Lee,Sang Woong Park,Hyun Ji Park,Young Min Bae,Tae Sik Sung,Hawon Cho,Chanjae Park,Sang Don Koh,Jae Gon Kim

doi:10.1038/s41598-019-42492-4

Kyung Chul Shin, In Hwa Lee + Show 8 more

Open Access

https://doi.org/10.1038/s41598-019-42492-4

Copy DOI

Abstract

Recent parallel studies clearly indicated that Merkel cells and the mechanosensitive piezo2 ion channel play critical roles in the light-touch somatosensation. Moreover, piezo2 was suggested to be a light-touch sensing ion channel without a role in pain sensing in mammals. However, biophysical characteristics of piezo2, such as single channel conductance and sensitivities to various mechanical stimuli, are unclear, hampering a precise understanding of its role in touch sensation. Here, we describe the biophysical properties of piezo2 in human Merkel cell carcinoma (MCC)-13 cells; piezo2 is a low-threshold, positive pressure-specific, curvature-sensitive, mechanically activated cation channel with a single channel conductance of ~28.6 pS. Application of step indentations under the whole-cell mode of the patch-clamp technique, and positive pressures ≥5 mmHg under the cell-attached mode, activated piezo2 currents in MCC-13 and human embryonic kidney 293 T cells where piezo2 was overexpressed. By contrast, application of a negative pressure failed to activate piezo2 in these cells, whereas both positive and negative pressure activated piezo1 in a similar manner. Our results are the first to demonstrate single channel recordings of piezo2. We anticipate that our findings will be a starting point for a more sophisticated understanding of piezo2 roles in light-touch sensation.

Highlights

Recent parallel studies clearly indicated that Merkel cells and the mechanosensitive piezo[2] ion channel play critical roles in the light-touch somatosensation
We describe the biophysical properties of piezo[2] in human Merkel cell carcinoma (MCC)-13 cells; piezo[2] is a low-threshold, positive pressure-specific, curvature-sensitive (CS), mechanically activated (MA) non-selective cation channel with a single channel conductance of ~28.6 pS
The observed MA currents in MCC-13 cells were inactivated with a decay time constant of 10.4 ± 1.3 (n = 6, at −40 mV, fitted with single exponential decay function) during a 100 ms-long step indentation (Fig. 1a)

Summary

Introduction

Recent parallel studies clearly indicated that Merkel cells and the mechanosensitive piezo[2] ion channel play critical roles in the light-touch somatosensation. We describe the biophysical properties of piezo[2] in human Merkel cell carcinoma (MCC)-13 cells; piezo[2] is a lowthreshold, positive pressure-specific, curvature-sensitive, mechanically activated cation channel with a single channel conductance of ~28.6 pS. Recent parallel studies clearly indicated that Merkel cells and the mechanosensitive piezo[2] ion channel expressed in Merkel cells and afferent Aβ fibers, play critical roles in the light-touch somatosensation[2,3,4]. We describe the biophysical properties of piezo[2] in human Merkel cell carcinoma (MCC)-13 cells; piezo[2] is a low-threshold, positive pressure-specific, curvature-sensitive (CS), mechanically activated (MA) non-selective cation channel with a single channel conductance of ~28.6 pS. Www.nature.com/scientificreports roles and suggest that, with its low-threshold, positive pressure-specific mechanosensitivity, piezo[2] is an optimized and specialized sensor of light touch

Methods

Results

Conclusion