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Emerging Concepts in Ion Channel Biophysics
Poster Abstracts
53
43-POS
Board 43
Transduction of Repetitive Mechanical Stimuli by Piezo Ion Channels
Amanda Lewis
, Alisa Cui, Malcolm McDonald, Jorg Grandl.
Duke University, Durham, NC, USA.
Many cell types experience repetitive mechanical stimuli, including vein endothelial cells during
pulsating blood flow, inner ear hair cells upon sound exposure, and skin cells and their
innervating DRG neurons when a finger sweeps across a textured surface or touches a vibrating
object. While mechanosensitive Piezo ion channels have been clearly implicated in sensing static
touch, their roles in transducing repetitive stimulations are less clear. Here, we perform
electrophysiological recordings of heterologously expressed mouse Piezo1 and Piezo2
responding to repetitive mechanical stimulations. Specifically, we stimulate channels by either
stretching the membrane using a high-speed pressure clamp or by directly probing the cell with a
fire-polished glass pipette driven by a piezoelectric motor. We find that Piezos can act as high-
pass, low-pass, or bandpass filters, depending on the stimulus waveform and duration. We then
use numerical simulations and human disease-related point mutations to demonstrate that
channel inactivation is the molecular mechanism underlying frequency filtering, and find
evidence for two kinetically distinct inactivated states. Finally, we show that frequency filtering
is conserved in rapidly-adapting mouse DRG neurons, which serve as low-pass filters when
transducing repetitive mechanical stimuli. Together, our results characterize Piezos as important
components in processing complex mechanical inputs, such as vibrations and blood flow, and
identify inactivation as a plastic mechanism for modulating the transduction of these stimuli.