Emerging Concepts in Ion Channel Biophysics

Emerging Concepts in Ion Channel Biophysics

Poster Abstracts

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.

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