Mammalian PIEZO channels rectify anionic currents.

Area of Science:

• Biophysics
• Molecular Biology
• Ion Channel Physiology

Background:

• Mammalian PIEZO channels (PIEZO1 and PIEZO2) are mechanosensitive ion channels primarily known for cation permeation.
• While PIEZO1 exhibits some chloride permeability, the mechanisms of anion permeation and rectification in PIEZO channels remain largely unexplored.
• Understanding anion permeation is crucial for a comprehensive view of PIEZO channel function in cellular physiology.

Purpose of the Study:

• To investigate the rectification properties of chloride currents through mammalian PIEZO1 and PIEZO2 channels.
• To explore the role of pore electrostatics in modulating anion permeation and rectification.
• To characterize the differences in rectification between cation and anion currents in PIEZO channels.

Main Methods:

• Electrophysiological recordings (e.g., patch-clamp) were used to measure sodium and chloride currents.
• Nonpermanent counterions were employed to isolate and measure specific ion currents.
• Molecular dynamics simulations were performed to analyze pore structure and electrostatic potential.

Main Results:

• Both PIEZO1 and PIEZO2 channels exhibit outward rectification of chloride currents, favoring chloride entry at voltages above its reversal potential.
• Sodium currents through PIEZO1 and PIEZO2 showed minimal rectification.
• A PIEZO1 mutant (9K) displayed inward rectification of chloride currents, correlating with positive electrostatic potential in the pore fenestrations.

Conclusions:

• Mammalian PIEZO channels possess an inherent rectification mechanism for chloride currents.
• The electrostatic properties of the PIEZO channel pore significantly influence and can tune chloride current rectification.
• These findings reveal a novel aspect of PIEZO channel ion selectivity and transport.