A Novel Triple-gate Model for Mechanosensitive Ion Channel Piezo1

Abstract

In this paper, we have developed a Hodgkin-Huxley (HH) -type triple-gate model for mechanosensitive ion channel Piezo1. The model can simulate currents elicited at an invariable saturation pressure (70 mmHg) and at multiple voltages from excised outside-out patches over-expressing Piezo1 in mouse neuroblastoma cells Neuro2A (N2A). The simulation ability of this model is attributed to the introduction of three modifications to the classic HH model. Firstly, varying numbers of gates at depolarized and hyperpolarized voltages are included. Secondly, the steady-state permissive probability of the inactivation gate decreases along with the increasing number of pressure stimuli at hyperpolarized voltages. Finally, the time constant of the activation gate becomes larger as its permissive probability increased at depolarized voltages following hyperpolarized voltages. Parameters are optimized by using the grid search method and Differential Evolution algorithm. The current characteristics at multiple voltages simulated by this model include outward rectification, irreversible desensitized state, and recovery from the desensitized state. The simulated results are in agreement with experimental observations, indicating that this model relates these experimental phenomena to the underlying gate kinetics.