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Publications

Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural Ppublish 2 citations

PubMed: 38479601 DOI: 10.1016/j.jbc.2024.107156

Analysis of pressure-activated Piezo1 open and subconductance states at a single channel level.

J Biol Chem 300(4):107156

Authors: Ghanim Ullah, Elena D Nosyreva, David Thompson, Victoria A Cuello, Luis G Cuello, Ruhma Syeda

Affiliations

  • Department of Physics, University of South Florida, Tampa, Florida, USA.
  • Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
  • Department of Cell Physiology and Molecular Biophysics, TTUHSC, Lubbock, Texas, USA.
  • Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, Texas, USA.

Abstract

Mechanically activated Piezo1 channels undergo transitions from closed to open-state in response to pressure and other mechanical stimuli. However, the molecular details of these mechanosensitive gating transitions are unknown. Here, we used cell-attached pressure-clamp recordings to acquire single channel data at steady-state conditions (where inactivation has settled down), at various pressures and voltages. Importantly, we identify and analyze subconductance states of the channel which were not reported before. Pressure-dependent activation of Piezo1 increases the occupancy of open and subconductance state at the expense of decreased occupancy of shut-states. No significant change in the mean open time of subconductance states was observed with increasing negative pipette pressure or with varying voltages (ranging from -40 to -100 mV). Using Markov-chain modeling, we identified a minimal four-states kinetic scheme, which recapitulates essential characteristics of the single channel data, including that of the subconductance level. This study advances our understanding of Piezo1-gating mechanism in response to discrete stimuli (such as pressure and voltage) and paves the path to develop cellular and tissue level models to predict Piezo1 function in various cell types.

MeSH

Cells

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