Ionic and Electrotonic Contributions to Short-Term Ventricular Action Potential Memory: An In Silico Study

Electrical restitution (ER) is a determinant of cardiac repolarization stability and can be measured as steady action potential (AP) duration (APD) at different pacing rates—the so-called dynamic restitution (ER<sub>dyn</sub>) curve—or as APD changes after pre- or post-mature stimulation...

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Bibliographic Details
Main Author: Massimiliano Zaniboni
Format: Article
Language:English
Published: MDPI AG 2025-07-01
Series:Computation
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Online Access:https://www.mdpi.com/2079-3197/13/7/175
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Summary:Electrical restitution (ER) is a determinant of cardiac repolarization stability and can be measured as steady action potential (AP) duration (APD) at different pacing rates—the so-called dynamic restitution (ER<sub>dyn</sub>) curve—or as APD changes after pre- or post-mature stimulations—the so-called standard restitution (ER<sub>s1s2</sub>) curve. Short-term AP memory (M<sub>s</sub>) has been described as the slope difference between the ER<sub>dyn</sub> and ER<sub>s1s2</sub> curves, and represents the information stored in repolarization dynamics due to previous pacing conditions. Although previous studies have shown its dependence on ion currents and calcium cycling, a systematic picture of these features is lacking. By means of simulations with a human ventricular AP model, I show that APD restitution can be described under randomly changing pacing conditions (ER<sub>rand</sub>) and M<sub>s</sub> derived as the slope difference between ER<sub>dyn</sub> and ER<sub>rand</sub>. Thus measured, M<sub>s</sub> values correlate with those measured using ER<sub>s1s2</sub>. I investigate the effect on M<sub>s</sub> of modulating the conductance of ion channels involved in AP repolarization, and of abolishing intracellular calcium transient. I show that M<sub>s</sub> is chiefly determined by ER<sub>dyn</sub> rather than ER<sub>rand,</sub> and that interventions that shorten/prolong APD tend to decrease/increase M<sub>s</sub>.
ISSN:2079-3197