A survey of pathways for mechano-electric coupling in the atria

Marta Varela Marta Varela,Aditi Roy,Jack Lee

doi:10.1016/j.pbiomolbio.2020.09.011

Marta Varela Marta Varela, Aditi Roy + Show 1 more

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https://doi.org/10.1016/j.pbiomolbio.2020.09.011

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Abstract

Mechano-electric coupling (MEC) in atrial tissue has received sparse investigation to date, despite the well-known association between chronic atrial dilation and atrial fibrillation (AF). Of note, no fewer than six different mechanisms pertaining to stretch-activated channels, cellular capacitance and geometric effects have been identified in the literature as potential players. In this mini review, we briefly survey each of these pathways to MEC. We then perform computational simulations using single cell and tissue models in presence of various stretch regimes and MEC pathways. This allows us to assess the relative significance of each pathway in determining action potential duration, conduction velocity and rotor stability. For chronic atrial stretch, we find that stretch-induced alterations in membrane capacitance decrease conduction velocity and increase action potential duration, in agreement with experimental findings. In the presence of time-dependent passive atrial stretch, stretch-activated channels play the largest role, leading to after-depolarizations and rotor hypermeandering. These findings suggest that physiological atrial stretches, such as passive stretch during the atrial reservoir phase, may play an important part in the mechanisms of atrial arrhythmogenesis.

Highlights

Arrhythmias are one of the major causes of death worldwide, accounting for 17 million deaths each year (Srinivasan and Schilling, 2018)
We focused on stretch-activated channels and stretch-induced changes in membrane capacitance, as we found these were some of the best candidates for easy inclusion in future atrial EP simulations: the selected pathways are comparatively well-characterised experimentally and amenable to being included in EP simulations with only minor alterations
We modelled mechano-electric coupling (MEC) pathways in single cells to gain an understanding of the impact of the proposed pathways on action potential morphology and properties such as action potential duration (APD) and resting membrane potential (RMP)

Summary

Introduction

Arrhythmias are one of the major causes of death worldwide, accounting for 17 million deaths each year (Srinivasan and Schilling, 2018). Despite being disturbances of the propagation of electrical signals in the heart, their devastating impact is caused by their perturbation of the heart’s mechanical function. This relationship between electrical impulses and cardiac contraction is mediated by well-known electro-mechanical coupling pathways, involving intracellular calcium handling. AF is characterised by a rapid, irregular and inefficient contraction of the atria. It affected 32.5 million people worldwide in 2010 and its incidence in Western Europe is expected to rise to 3% of all adults aged over 20 by 2030 (Kirchhof et al, 2016). AF is often accompanied by substantial decreases in quality of life and a high rate of hospitalizations (Calkins et al, 2012) and, altogether, the economic burden of AF already amounts to 1% of total healthcare costs in the UK (Kirchhof et al, 2016)

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