In Silico Modeling and Validation of the Effect of Calcium-Activated Potassium Current on Ventricular Repolarization in Failing Myocytes.

IF 6.7 2区医学 Q1 COMPUTER SCIENCE, INFORMATION SYSTEMS IEEE Journal of Biomedical and Health Informatics Pub Date : 2024-11-08 DOI:10.1109/JBHI.2024.3495027

Marta Gomez, Jesus Carro, Esther Pueyo, Alba Perez, Aida Olivan, Violeta Monasterio

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Abstract

Objective: The pathophysiological role of the small conductance calcium-activated potassium (SK) channels in human ventricular myocytes remains unclear. Experimental studies have reported upregulation of in pathological states, potentially contributing to ventricular arrhythmias. In heart failure (HF) patients, the upregulation of SK channels could be an adaptive physiological response to shorten the action potential duration (APD) under conditions of reduced repolarization reserve. In this work, we aimed at uncovering the contribution of SK channels to ventricular repolarization in failing myocytes.

Methods: We extended an in silico electrophysiological model of human ventricular failing myocytes by including a representation of the SK channel activity. To calibrate the maximal SK current conductance (G _SK), we simulated action potentials (APs) at different pacing frequencies and matched the changes in AP duration induced by SK channel inhibition or activation to available experimental data.

Results: The optimal value obtained for G_SK was 4.288 μ S/ μF in mid-myocardial cells, and 6.4 μS/ μF for endocardial and epicardial cells. The simulated SK block-induced effects were consistent with experimental evidence. 1-D simulations of a transmural ventricular fiber indicated that SK channel block may prolong the QT interval and increase the transmural dispersion of repolarization, potentially increasing the risk of arrhythmia in HF.

Conclusion: Our results highlight the importance of considering the SK channels to improve the characterization of HF-induced ventricular remodeling. Simulations across various scenarios in 0-D and 1-D scales suggest that pharmacological SK channel inhibition could lead to adverse effects in failing ventricles.

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钙激活钾电流对衰竭肌细胞心室复极化影响的硅学建模和验证

目的：人类心室肌细胞中的小电导钙激活钾（SK）通道的病理生理作用仍不清楚。实验研究表明，SK 通道在病理状态下上调，可能导致室性心律失常。在心力衰竭（HF）患者中，SK 通道的上调可能是一种适应性生理反应，可在复极化储备减少的情况下缩短动作电位持续时间（APD）。在这项工作中，我们旨在揭示 SK 通道对衰竭心肌细胞心室复极化的贡献：方法：我们扩展了人类心室衰竭肌细胞的硅电生理模型，在其中加入了 SK 通道活动的表征。为了校准SK通道的最大电流电导（G SK），我们模拟了不同起搏频率下的动作电位（AP），并将SK通道抑制或激活引起的AP持续时间变化与现有实验数据进行了比对：在心肌中层细胞中，GSK 的最佳值为 4.288 μ S/ μF，在心内膜和心外膜细胞中，最佳值为 6.4 μ S/ μF。模拟的 SK 区块诱导效应与实验证据一致。对跨膜心室纤维的一维模拟表明，SK 通道阻滞可能会延长 QT 间期并增加复极化的跨膜弥散，从而可能增加高频心律失常的风险：我们的研究结果凸显了考虑 SK 通道对改善高频诱导的心室重塑特征的重要性。0-D和1-D尺度的各种模拟表明，药理SK通道抑制可能会对衰竭心室产生不良影响。

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来源期刊

IEEE Journal of Biomedical and Health Informatics COMPUTER SCIENCE, INFORMATION SYSTEMS-COMPUTER SCIENCE, INTERDISCIPLINARY APPLICATIONS

CiteScore

13.60

自引率

6.50%

发文量

1151

期刊介绍： IEEE Journal of Biomedical and Health Informatics publishes original papers presenting recent advances where information and communication technologies intersect with health, healthcare, life sciences, and biomedicine. Topics include acquisition, transmission, storage, retrieval, management, and analysis of biomedical and health information. The journal covers applications of information technologies in healthcare, patient monitoring, preventive care, early disease diagnosis, therapy discovery, and personalized treatment protocols. It explores electronic medical and health records, clinical information systems, decision support systems, medical and biological imaging informatics, wearable systems, body area/sensor networks, and more. Integration-related topics like interoperability, evidence-based medicine, and secure patient data are also addressed.