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Bioinformatics, Computational and Systems Biology

Bioinformatics, Computational and Systems Biology - Poster Session E

M1 - A GUI for Simulating Electrophysiology and Calcium Dynamics in Vascular Cells

Saturday, October 11, 2025

10:00 AM - 11:00 AM PDT

Location: Exhibit Hall F, G & H

Presenting Author(s)

Catherine Alexander

Student
Florida International University, United States

Co-Author(s)

Paulina Perez

Coulter Undergraduate Research Program (CURE) Researcher
Florida International University
Miramar, Florida, United States

Co-Author(s)

Niloufar Khakpour, PhD

Research assistant
Florida International University
Miami, Florida, United States

Primary Investigator(s)

Nikolaos M. Tsoukias

Professor
Florida International University
Miami, Florida, United States

Introduction: : Mathematical models of electrophysiological activity and calcium signaling have played a critical role in understanding excitable cells such as neurons and cardiomyocytes. However, vascular cells, including mural cells (MCs) such as vascular smooth muscle cells (SMCs) and pericytes (PCs), as well as endothelial cells (ECs), remain comparatively underrepresented despite their essential role in regulating cerebral blood flow and microvascular tone. These cells mediate key aspects of cerebrovascular function including pressure sensing, blood flow modulation, and signal transduction.
To address this gap, we developed an interactive Graphical User Interface (GUI) that simulates the electrophysiological and biomechanical behavior of MCs and ECs. The GUI enables users to manipulate key variables—such as ion concentrations, extracellular potassium, agonists, and applied currents—and observe real-time outputs, including membrane potential (Vₘ) and intracellular calcium concentration ([Ca²⁺]ᵢ). For mural cells, the GUI includes a biomechanics module to simulate pressure-induced changes in vessel diameter and tone. By bridging complex mathematical models with an accessible, visual platform, this tool offers a valuable resource for both research and education in cerebrovascular physiology and disease.

Materials and

Methods: : We developed cell-specific mathematical models to simulate the electrophysiological behavior of SMCs, PCs, and ECs in cerebral microcirculation. These models reproduce Vₘ and [Ca²⁺]ᵢ dynamics in response to physiological stimuli, expanding on prior models by Kapela et al. (2008) and Silva et al. (2007). Each model includes three compartments: the plasma membrane, cytosol, and intracellular calcium store. A schematic diagram of the SMC model is presented in Figure 1. The membrane contains detailed representations of ion channels (e.g., KCa, KATP, KV, Kir, VOCCs, SOC, NSC), pumps, exchangers, and receptors based on experimental data. Membrane transporters such as Na⁺/K⁺-ATPase, PMCA, Na⁺/Ca²⁺ exchangers, and cotransporters maintain ionic homeostasis. Calcium stores are regulated by IP₃Rs, RyRs, and SERCA pumps.
To reduce computational complexity, currents without calcium- or voltage-dependent gating can be linearized and grouped as background current. This preserves core behavior while improving efficiency. A custom GUI enables users to apply stimuli (e.g., agonists, potassium, current, mechanical forces) and observe Vₘ and [Ca²⁺]ᵢ responses. The GUI allows real-time adjustment of ion channel densities and includes a panel for visualizing time-resolved ion currents, aiding in mechanistic interpretation.
This framework simulates both normal and diseased states and lays the foundation for multiscale models of cerebral blood flow regulation, integrating vascular topology, hemodynamics, and oxygen transport to brain tissue.

Results, Conclusions, and Discussions:: Simulations performed using the GUI accurately reproduced key electrophysiological and biomechanical responses. In SMC simulations, pressure ramps induced membrane depolarization, increased [Ca²⁺]ᵢ, and led to vessel constriction. The interface allows users to track specific ion channel currents, highlighting how individual conductances are upregulated or suppressed under different conditions. This capability supports mechanistic insight into calcium signaling and reveals how channel behavior may differ in pathological states. In EC simulations, stimulation with norepinephrine or increased extracellular potassium triggered appropriate depolarization or hyperpolarization responses, validating the model's responsiveness to both chemical signals and ionic perturbations.
Overall, the GUI integrates electrophysiology, ion channel behavior, calcium signaling, and MCs biomechanics, providing a comprehensive and interactive tool for simulating vascular cell function. Its flexibility across both healthy and disease-mimicking scenarios makes it a valuable resource for both research and education, bridging the gap between mathematical modeling and physiological understanding of cerebral microcirculation.

Acknowledgements and/or References (Optional): : This study was supported by NIH Grant R01NS119971 .