Chloroquine effect on human atrial action potential under normal conditions and during paroxysmal and chronic atrial fibrillation. A simulation study

Abstract

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. If the paroxysmal AF (pAF) is not treated it could become chronic or permanent AF (cAF). Blockade of inward rectifying potassium (IK1) and acetylcholine-activated potassium (IKACh) currents by the antimalarial drug chloroquine could play a role as antiarrhythmic drug in human AF. We simulated the effects of chloroquine on human atrial cell and studied its effect on atrial action potential under normal conditions and during pAF and cAF. For this, we modified a human cell model to obtain pAF and cAF models, and we developed a model of chloroquine effects on IK1 and IKACh; this model fit well the experimental data. Our results show that chloroquine blocks both currents in a fraction greater as the concentration increases, prolonging its action in time, which results in an APD lengthening. Chloroquine has a greater effect on pAF conditions and high chloroquine concentration is needed to achieve similar effects in cAF. To our knowledge, this is the first work that has developed mathematical models of chloroquine effects on IK1 and IKACh currents to study its effect on human atrial action potential.