Action Potential Simulation

An action potential (AP) is a transient, all-or-nothing reversal of the membrane potential driven by the sequential activation and inactivation of voltage-gated ion channels. In cardiac myocytes, the AP lasts several hundred milliseconds and comprises five distinct phases: rapid depolarization (phase 0, Na⁺ influx via Nav1.5), early repolarization (phase 1, transient outward K⁺ current), the plateau (phase 2, balanced L-type Ca²⁺ influx and K⁺ efflux), repolarization (phase 3, delayed rectifier K⁺ currents), and the resting potential (phase 4, inward rectifier K⁺ current).

This simulation implements the O'Hara–Rudy (2011) dynamic model of the human ventricular action potential. The model includes 15 transmembrane currents, intracellular calcium handling, and three cell-type variants (endocardial, epicardial, mid-myocardial) that reproduce the transmural heterogeneity observed experimentally.

Use the Settings tab to scale individual ion channel conductances between 0 and 1. This allows you to simulate the effect of selective channel block — for example, reducing I_Kr (hERG) mimics the action of class III antiarrhythmic drugs and prolongs the AP duration, while reducing I_CaL shortens the plateau phase. Preset drug profiles are available for rapid exploration.

The model is valuable for understanding how specific channel mutations, drug interactions, or conductance changes translate into AP prolongation or shortening — key determinants of arrhythmogenic risk in cardiac safety pharmacology.

The first step toward preventing sudden cardiac death is understanding the basic mechanisms of ventricular arrhythmias at the level of ion channel currents and the single myocyte action potential (AP), using both experiments and theoretical models (e.g. O'Hara et al 2011).

Many drugs influence cardiac electrical activity by blocking one or more ion channels. Open the Settings tab and adjust the conductance of individual ion channels: a value of 1 represents normal conductance, 0 represents complete channel block, and intermediate values simulate partial inhibition.

Try it yourself. Change one channel at a time and observe how the action potential responds:

• Reduce I_Kr (hERG): repolarization becomes slower and the action potential is prolonged — an effect associated with many hERG-blocking drugs and an important consideration in cardiac safety assessment.
• Reduce I_CaL: Ca²⁺ influx during the plateau decreases, shortening the plateau and typically reducing action-potential duration.
• Reduce I_Na: the rapid depolarization phase becomes slower and the upstroke is reduced.

You can also select a preset drug profile to explore the combined effects of blocking several ion channels simultaneously.

What should you look for? Pay particular attention to changes in the speed of depolarization, the height and duration of the plateau, the rate of repolarization, and the overall action-potential duration (APD). Compare different ion-channel settings, drug profiles, and ventricular cell types — even a selective change in one current can alter the electrical behaviour of the whole cell. These relationships are central to cardiac safety pharmacology, where drug-induced prolongation or shortening of the action potential can indicate changes in arrhythmogenic risk.