Myocardial action potential duration (MAPD)

Myocardial action potential duration (MAPD) is a physiological measurement representing the time from the onset of depolarization to the completion of repolarization in cardiac muscle cells (StatPearls, 2023). It is not a single molecular target but rather a complex electrophysiological phenotype determined by the integrated activity of multiple ion channels, including sodium (Nav1.5), calcium (Cav1.2), and various potassium channels such as hERG (KCNH2) and KCNQ1 (PubMed, PMID: 28838937). MAPD is a critical determinant of the cardiac refractory period; its prolongation is a hallmark of Long QT Syndrome and a major risk factor for Torsades de Pointes, a potentially fatal ventricular arrhythmia (NIH, 2022). Pharmacological modulation of MAPD is a primary strategy for Class III antiarrhythmic drugs, which typically prolong the duration to prevent re-entry, but unintended MAPD prolongation by non-cardiac drugs is a significant safety concern in drug development (FDA, ICH S7B). Consequently, MAPD serves as a vital biomarker for cardiac safety, often monitored via the surrogate QT interval on an electrocardiogram (Nature Reviews Cardiology, 2018).

Other names

Action potential durationAPDCardiac action potential durationVentricular action potential durationMonophasic action potential duration

Drugs modulate myocardial action potential duration primarily by inhibiting or enhancing the conductance of specific ion channels, such as the rapid delayed rectifier potassium current (IKr) mediated by hERG, or the L-type calcium current (ICa,L).