LongQt: A cardiac electrophysiology simulation platform

Önal, Birce; Gratz, Daniel; Hund, Thomas J.

doi:10.1016/j.mex.2016.11.002

Cited by 10 publications

(12 citation statements)

References 23 publications

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“…Ion channel kinetics were simulated using an existing wellvalidated model of the rabbit SAN cell implemented in LongQt simulation software [23,24] (Figure 1A). Briefly, the LongQt simulation software has three main user interfaces: the grid editor, the main user interface, and the grapher.…”

Section: Methodsmentioning

confidence: 99%

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Synchronization of Pacemaking in the Sinoatrial Node: A Mathematical Modeling Study

et al. 2018

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Computational studies using mathematical models of the sinoatrial node (SAN) cardiac action potential (AP) have provided important insight into the fundamental nature of cell excitability, cardiac arrhythmias, and potential therapies. While the impact of ion channel dynamics on SAN pacemaking has been studied, the governing dynamics responsible for regulating spatial and temporal control of SAN synchrony remain elusive. Here, we attempt to develop methods to explore cohesion in a network of coupled spontaneously active SAN cells. We present the updated version of a previously published graphical user interface LongQt: a cross-platform, threaded application for advanced cardiac electrophysiology studies that does not require advanced programming skills. We incorporated additional features to the existing LongQt platform that allows users to (1) specify heterogeneous gap junction conductivity across a multicellular grid, and (2) set heterogeneous ion channel conductance across a multicellular grid. We developed two methods of characterizing the synchrony of SAN tissue based on alignment of activation in time and similarity of voltage peaks among clusters of functionally related cells. In pairs and two-dimensional grids of coupled cells, we observed a range of conductivities (0.00014-0.00033 1/ -cm) in which the tissue was more susceptible to developing asynchronous spontaneous pro-arrhythmic behavior (e.g., spiral wave formation). We performed parameter sensitivity analysis to determine the relative impact of ion channel conductances on cycle length (CL), diastolic and peak voltage, and synchrony measurements in isolated and coupled cell pairs. We also defined measurements of evaluating synchrony based on peak AP voltage and the rate of wave propagation. Cell-to-cell coupling had a non-linear effect on the relationship between ion channel conductances, AP properties, and synchrony measurements. Our simulations demonstrate that conductivity plays an important role in regulating synchronous firing of heterogeneous SAN tissue, and demonstrate how to evaluate the role of coupling and ion channel conductance in pairs and grids of SAN cells. We anticipate that the approach outlined here will facilitate identification of key cell-and tissue-level factors responsible for cardiac disease.

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Section: Methodsmentioning

confidence: 99%

“…To reduce these barriers a cross-platform user interface called LongQt has been developed for advanced cardiac electrophysiology and arrhythmia simulations [23]. Here, we present an extended user interface for LongQt, which adds support for performing advanced multicellular simulations.…”

Section: Introductionmentioning

confidence: 99%

Synchronization of Pacemaking in the Sinoatrial Node: A Mathematical Modeling Study

et al. 2018

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“…Computer simulations were performed to predict mechanism for delayed after depolarizations (DADs) in the absence of overt changes to baseline action potential. The Bondarenko murine ventricular myocyte cell model ( 16 ) in the LongQt platform ( 32 ) was used for all simulations. In the Bondarenko model, DADs are triggered when concentration of Ca 2+ -bound calsequestrin (peak CSQN) in the sarcoplasmic reticulum (SR) reaches 11.5 (mM).…”

Section: Methodsmentioning

confidence: 99%

Giant ankyrin-G regulates cardiac function

Cavus

Williams

Musa

et al. 2021

Journal of Biological Chemistry

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Cardiovascular disease (CVD) remains the most common cause of adult morbidity and mortality in developed nations. As a result, predisposition for CVD is increasingly important to understand. Ankyrins are intracellular proteins required for the maintenance of membrane domains. Canonical ankyrin-G (AnkG) has been shown to be vital for normal cardiac function, specifically cardiac excitability, via targeting and regulation of the cardiac voltage-gated sodium channel. Noncanonical (giant) AnkG isoforms play a key role in neuronal membrane biogenesis and excitability, with evidence for human neurologic disease when aberrant. However, the role of giant AnkG in cardiovascular tissue has yet to be explored. Here, we identify giant AnkG in the myocardium and identify that it is enriched in 1-week-old mice. Using a new mouse model lacking giant AnkG expression in myocytes, we identify that young mice displayed a dilated cardiomyopathy phenotype with aberrant electrical conduction and enhanced arrhythmogenicity. Structural and electrical dysfunction occurred at 1 week of age, when giant AnkG was highly expressed and did not appreciably change in adulthood until advanced age. At a cellular level, loss of giant AnkG results in delayed and early afterdepolarizations. However, surprisingly, giant AnkG cKO myocytes display normal I Na , but abnormal myocyte contractility, suggesting unique roles of the large isoform in the heart. Finally, transcript analysis provided evidence for unique pathways that may contribute to the structural and electrical findings shown in giant AnkG cKO animals. In summary, we identify a critical role for giant AnkG that adds to the diversity of ankyrin function in the heart.

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“…Model testing and integration into the Grandi atrial myocyte was written in c++17, using the LongQt library 0.5. LongQt is available at hundlab.engineering.osu.edu/research/LongQt with model code available at hundlab/LongQt-model in branch atrial-model [ 31 ].…”

Section: Methodsmentioning

confidence: 99%

Statistical Approach to Incorporating Experimental Variability into a Mathematical Model of the Voltage-Gated Na+ Channel and Human Atrial Action Potential

Gratz

Winkle

Weinberg

et al. 2021

Cells

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The voltage-gated Na+ channel Nav1.5 is critical for normal cardiac myocyte excitability. Mathematical models have been widely used to study Nav1.5 function and link to a range of cardiac arrhythmias. There is growing appreciation for the importance of incorporating physiological heterogeneity observed even in a healthy population into mathematical models of the cardiac action potential. Here, we apply methods from Bayesian statistics to capture the variability in experimental measurements on human atrial Nav1.5 across experimental protocols and labs. This variability was used to define a physiological distribution for model parameters in a novel model formulation of Nav1.5, which was then incorporated into an existing human atrial action potential model. Model validation was performed by comparing the simulated distribution of action potential upstroke velocity measurements to experimental measurements from several different sources. Going forward, we hope to apply this approach to other major atrial ion channels to create a comprehensive model of the human atrial AP. We anticipate that such a model will be useful for understanding excitability at the population level, including variable drug response and penetrance of variants linked to inherited cardiac arrhythmia syndromes.

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LongQt: A cardiac electrophysiology simulation platform

Abstract: Graphical abstract

Cited by 10 publications

References 23 publications

Synchronization of Pacemaking in the Sinoatrial Node: A Mathematical Modeling Study

Synchronization of Pacemaking in the Sinoatrial Node: A Mathematical Modeling Study

Giant ankyrin-G regulates cardiac function

Statistical Approach to Incorporating Experimental Variability into a Mathematical Model of the Voltage-Gated Na+ Channel and Human Atrial Action Potential

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