Related Experiment Video
Updated: Jul 10, 2026
09:09
In Silico Clinical Trials for Cardiovascular Disease
Published on: May 27, 2022
Action potential alternans in LQT3 syndrome: a simulation study
Felipe Alonso-Atienza1, Jesús Requena-Carrión, José Luis Rojo-Alvarez
1Department of Signal Theory and Communications, Universidad Rey Juan Carlos, Camino del Molino s/n, Fuenlabrada, Madrid, Spain. falonso@tsc.uc3m.es
Summary
Long QT syndrome type-3 (LQT3), caused by SCN5A mutations, can lead to dangerous heart rhythms. Dynamical analysis reveals that LQT3 mutant cells exhibit alternans, explaining rate-dependent arrhythmias.
Area of Science:
- Cardiology
- Computational Biology
- Molecular Biology
Background:
- Long QT syndrome type-3 (LQT3) is an inherited cardiac disorder linked to SCN5A gene mutations.
- LQT3 is associated with ventricular arrhythmias and sudden cardiac death, particularly at low heart rates.
- Early afterdepolarizations (EADs) and spontaneous discharges in action potentials are implicated in LQT3 arrhythmia triggers.
Purpose of the Study:
- To perform a dynamical analysis of LQT3 at the cellular level.
- To investigate beat-to-beat Action Potential Duration (APD) variations in LQT3 using a Markovian model of the DeltaKPQ mutation.
Main Methods:
- Utilized a detailed Markovian model for the DeltaKPQ mutation associated with LQT3.
- Employed a long-term stimulation protocol to study APD variations.
- Compared dynamical characteristics of DeltaKPQ mutant cells with wild-type (WT) cells.
Main Results:
- DeltaKPQ mutant cells demonstrated APD alternans within a specific range of stimulation frequencies.
- The frequency range for APD alternans correlated with the severity of EADs in the action potential.
- Found significant differences in dynamical behavior between mutant and WT cardiac cells.
Conclusions:
- Dynamical analysis of paced cardiac cells offers valuable insights into LQT3 mechanisms.
- APD alternans in LQT3 mutant cells contribute to the understanding of rate-dependent arrhythmias.
- The study highlights the importance of dynamic characteristics in cardiac tissue for arrhythmia mechanisms.
Related Concept Videos
01:28Action Potential: Phases of Stimulation
The action potential is a complex electrical event that occurs in excitable cells, such as neurons and muscle cells. It consists of several distinct phases, each with specific characteristics.
Resting Phase:
In this phase, the cell's membrane is at its resting potential, typically around -70 millivolts (mV) for neurons. Inside the cell, there is a higher concentration of potassium ions (K+) and a lower concentration of sodium ions (Na+). Voltage-gated sodium channels are closed, and...
Resting Phase:
In this phase, the cell's membrane is at its resting potential, typically around -70 millivolts (mV) for neurons. Inside the cell, there is a higher concentration of potassium ions (K+) and a lower concentration of sodium ions (Na+). Voltage-gated sodium channels are closed, and...
01:23Propagation of Action Potentials
The propagation of an action potential refers to the process by which a nerve impulse, or "action potential," travels along a neuron.
Neurons (nerve cells) have a resting membrane potential, with a slightly negative charge inside compared to outside. This is maintained by ion channels, such as sodium (Na+) and potassium (K+) channels, which control the flow of ions. When a stimulus, like a touch or a signal from another neuron, triggers the neuron, sodium channels open, allowing sodium ions to...
Neurons (nerve cells) have a resting membrane potential, with a slightly negative charge inside compared to outside. This is maintained by ion channels, such as sodium (Na+) and potassium (K+) channels, which control the flow of ions. When a stimulus, like a touch or a signal from another neuron, triggers the neuron, sodium channels open, allowing sodium ions to...
01:30Cardiac Action Potential
Cardiac action potentials are essential for proper heart function, enabling the rhythmic contractions needed for adequate blood circulation. Nodal cells and Purkinje fibers, specialized for electrical conduction, generate these action potentials.
The cardiac action potential process involves a series of phases characterized by the movement of ions across the cardiac cell membranes, leading to the depolarization and repolarization of the cardiac myocytes.
Ionic Basis of Cardiac Action Potentials
The cardiac action potential process involves a series of phases characterized by the movement of ions across the cardiac cell membranes, leading to the depolarization and repolarization of the cardiac myocytes.
Ionic Basis of Cardiac Action Potentials
01:14Action Potential
Neurons communicate by firing action potentials—the electrochemical signal that is propagated along the axon. The signal results in the release of neurotransmitters at axon terminals, thereby transmitting information to the nervous system. An action potential is a specific "all-or-none" change in membrane potential that results in a rapid spike in voltage.
Membrane potential in neurons
Neurons typically have a resting membrane potential of about -70 millivolts (mV). When they receive...
Membrane potential in neurons
Neurons typically have a resting membrane potential of about -70 millivolts (mV). When they receive...
01:12Antiarrhythmic Drugs: Class III Agents as Potassium Channel Blockers
Class III antiarrhythmic drugs are a group of medications that can prolong action potentials in the heart. They achieve this by blocking potassium channels or enhancing inward currents from sodium channels. However, these drugs have a unique property of "reverse use-dependence," which is most pronounced at slower heart rates and can lead to torsades de pointes—a specific type of arrhythmia. However, it is essential to note that excessive QT interval prolongation—a measure of the heart's...
01:41Action Potentials
Overview