当前位置： SCI文献检索 > Frontiers in Physiology期刊下所有文献 > Simulation of the Effects of Extracellular Calcium Changes Leads to a Novel Computational Model of Human Ventricular Action Potential With a Revised Calcium Handling.

Simulation of the Effects of Extracellular Calcium Changes Leads to a Novel Computational Model of Human Ventricular Action Potential With a Revised Calcium Handling.

Abstract：

:The importance of electrolyte concentrations for cardiac function is well established. Electrolyte variations can lead to arrhythmias onset, due to their important role in the action potential (AP) genesis and in maintaining cell homeostasis. However, most of the human AP computer models available in literature were developed with constant electrolyte concentrations, and fail to simulate physiological changes induced by electrolyte variations. This is especially true for Ca2+, even in the O'Hara-Rudy model (ORd), one of the most widely used models in cardiac electrophysiology. Therefore, the present work develops a new human ventricular model (BPS2020), based on ORd, able to simulate the inverse dependence of AP duration (APD) on extracellular Ca2+ concentration ([Ca2+]o), and APD rate dependence at 4 mM extracellular K+. The main changes needed with respect to ORd are: (i) an increased sensitivity of L-type Ca2+ current inactivation to [Ca2+]o; (ii) a single compartment description of the sarcoplasmic reticulum; iii) the replacement of Ca2+ release. BPS2020 is able to simulate the physiological APD-[Ca2+]o relationship, while also retaining the well-reproduced properties of ORd (APD rate dependence, restitution, accommodation and current block effects). We also used BPS2020 to generate an experimentally-calibrated population of models to investigate: (i) the occurrence of repolarization abnormalities in response to hERG current block; (ii) the rate adaptation variability; (iii) the occurrence of alternans and delayed after-depolarizations at fast pacing. Our results indicate that we successfully developed an improved version of ORd, which can be used to investigate electrophysiological changes and pro-arrhythmic abnormalities induced by electrolyte variations and current block at multiple rates and at the population level.

journal_name

Front Physiol

journal_title

Frontiers in physiology

authors

Bartolucci C,Passini E,Hyttinen J,Paci M,Severi S

doi

10.3389/fphys.2020.00314

subject

Has Abstract

pub_date

2020-04-15 00:00:00

pages

314

issn

1664-042X

journal_volume

pub_type

杂志文章

在线工具

Simulation of the Effects of Extracellular Calcium Changes Leads to a Novel Computational Model of Human Ventricular Action Potential With a Revised Calcium Handling.