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Strategies for prolonging ventricular action potential duration without increasing transmural dispersion of repolarization.

Physiological reports·2025

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Multichannel modulation of depolarizing and repolarizing ion currents increases the positive rate-dependent action potential prolongation.

Physiological reports·2023

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Related Experiment Video

Updated: Sep 6, 2025

Voltage-Dependent Potassium Current Recording on H9c2 Cardiomyocytes via the Whole-Cell Patch-Clamp Technique

Voltage-Dependent Potassium Current Recording on H9c2 Cardiomyocytes via the Whole-Cell Patch-Clamp Technique

Published on: November 11, 2022

Positive rate-dependent action potential prolongation by modulating potassium ion channels.

¹Department of Computer Systems, New York City College of Technology, Doctoral Program in Computer Science, Graduate Center, City University of New York, New York, New York, USA.

Physiological Reports

|June 24, 2022

Summary

Pharmacological agents can prolong action potential duration (APD) differently at slow versus fast heart rates. Strategies that prolong APD more at fast rates may improve antiarrhythmic effects while reducing risks.

Keywords:

computer models positive rate dependence potassium ion channels

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Area of Science:

Cardiovascular Physiology
Computational Biology
Pharmacology

Background:

Reverse rate dependence of antiarrhythmic drugs can limit efficacy.
Excessive action potential duration (APD) prolongation at slow rates may cause pro-arrhythmic effects.

Purpose of the Study:

Investigate computational models of ventricular action potential to understand rate-dependent APD prolongation.
Identify strategies to optimize APD prolongation for antiarrhythmic effects.

Main Methods:

Computer modeling of ventricular action potential.
Simulated interventions targeting specific potassium currents (I_Ks, I_Kr, I_K1).

Main Results:

Accelerating phase 2 repolarization (I_Ks) and decelerating phase 3 (I_Kr, I_K1 block) yielded positive rate dependence.
Blocking specific potassium channels resulted in reverse or moderate positive rate dependence.
Limiting I_K1 block to 50% achieved strong positive rate dependence with moderate repolarization reserve decrease.

Conclusions:

Combining I_Ks activators with I_Kr and I_K1 blockers may maximize antiarrhythmic benefits.
This approach could minimize pro-arrhythmic risks by optimizing APD prolongation at fast heart rates.