A Simple Voltage-Modulated Markov Chain Model for the Piezo1 Ion Channel to Investigate Electromechanical Pacing

TL;DR

This paper introduces a voltage-modulated Markov chain model for Piezo1 ion channels, capturing their stretch response and integrating into cardiac cell models to study electromechanical pacing effects.

Contribution

A novel mathematical model of Piezo1 channels based on Markov chains that reproduces experimental data and is integrated into cardiomyocyte models for electromechanical analysis.

Findings

Model accurately reproduces experimental Piezo1 behavior.

Integrated model shows Piezo1's role in electromechanical responses.

Qualitative agreement with pacing protocol observations.

Abstract

Piezo1 ion channels are voltage-modulated, stretch-activated ion channels involved in a variety of important physiological and pathophysiological processes, as for example cardiovascular development and homeostasis. Since its discovery, it has been known that this type of ion channel desensitizes when exposed to stretch. However, recent experiments on Piezo1 ion channels have uncovered that their stretch response is qualitatively different when exposed to positive electrochemical driving forces, where the desensitization is reset. In this work, we propose a novel voltage-modulated mathematical model of Piezo1 based on a continuous-time Markov chain. We show that our Piezo1 model is able to quantitatively reproduce a wide range of experimental observations. Furthermore, we integrate our new ion channel model into the Mahajan-Shiferaw ventricular cardiomyocyte model to study the effect of electromechanical pacing at the cellular scale. This integrated cell model is able to qualitatively reproduce some aspects of the experimental observations regarding the rate-dependence of electromechanical pacing protocols. Our studies suggest that the Piezo1 ion channel is an important component that significantly contributes to the electromechanical coupled response of cardiomyocytes.