Mathematical Model of an Adult Human Atrial Cell

TLDR

The study builds on a prior rabbit atrial myocyte model, motivated by differences in repolarizing currents between human and rabbit atria. The model uses a Hodgkin–Huxley–type sarcolemmal circuit linked to a fluid compartment that tracks ionic concentrations, with special emphasis on the sustained outward K⁺ current (I_sus) that influences action‑potential duration. The model, calibrated to voltage‑clamp data, accurately reproduces human atrial action potentials and shows that peak and plateau shapes are governed mainly by transient outward K⁺, I_sus, and L‑type Ca²⁺ currents, with I_sus’s influence modulated by baseline levels of these currents and varying with physiological or disease conditions.

Abstract

Abstract —We have developed a mathematical model of the human atrial myocyte based on averaged voltage-clamp data recorded from isolated single myocytes. Our model consists of a Hodgkin-Huxley–type equivalent circuit for the sarcolemma, coupled with a fluid compartment model, which accounts for changes in ionic concentrations in the cytoplasm as well as in the sarcoplasmic reticulum. This formulation can reconstruct action potential data that are representative of recordings from a majority of human atrial cells in our laboratory and therefore provides a biophysically based account of the underlying ionic currents. This work is based in part on a previous model of the rabbit atrial myocyte published by our group and was motivated by differences in some of the repolarizing currents between human and rabbit atrium. We have therefore given particular attention to the sustained outward K + current ( I sus ), which putatively has a prominent role in determining the duration of the human atrial action potential. Our results demonstrate that the action potential shape during the peak and plateau phases is determined primarily by transient outward K + current, I sus , and L-type Ca 2+ current ( I Ca,L ) and that the role of I sus in the human atrial action potential can be modulated by the baseline sizes of I Ca,L , I sus , and the rapid delayed rectifier K + current. As a result, our simulations suggest that the functional role of I sus can depend on the physiological/disease state of the cell.