Ionic Selectivity and Permeation Properties of Human PIEZO1 Channels

Area of Science:

• Biophysics
• Molecular Biology
• Ion Channel Physiology

Background:

• PIEZO channels are mechanically gated ion channels crucial for mechanotransduction.
• Human PIEZO1 (hPIEZO1) is a key player in sensing mechanical stimuli.
• Understanding ion selectivity is vital for elucidating channel function.

Purpose of the Study:

• Characterize the ion selectivity of the human PIEZO1 channel.
• Investigate the permeation of various cations, including alkali, organic, and divalent ions.
• Determine the impact of different ions on channel conductance and gating properties.

Main Methods:

• Electrophysiological recordings (cell-attached patch-clamp).
• Systematic variation of extracellular ion concentrations (K+, Na+, Cs+, Li+, Ba2+, Ca2+, Mg2+, Mn2+, TMA+, TEA+).
• Analysis of single-channel currents and conductances at defined membrane potentials.

Main Results:

• hPIEZO1 is permeable to all tested monovalent cations, with Li+ showing significantly lower conductance (~23 pS) compared to Cs+, Na+, and K+ (35-55 pS at -100 mV).
• Divalent cations (Ba2+, Ca2+, Mg2+) permeated slowly, reduced K+ permeability, and lowered channel opening rates.
• Organic cations (TMA+, TEA+) also permeated slowly and attenuated K+ currents.
• K+ conductance saturated at ~45 pS with a K+ dissociation constant (KD) of 32 mM.
• Cytochalasin D increased channel opening frequency, suggesting reduced mechanoprotection.

Conclusions:

• hPIEZO1 exhibits distinct ion selectivity profiles for monovalent and divalent cations.
• Divalent ions can significantly modulate hPIEZO1 channel function by altering permeability and gating.
• Actin dynamics play a role in regulating hPIEZO1 mechanosensitivity.