Organophosphate-modulated cardiac membrane currents: computer study of the genesis of LQTS

Abstract

An important clinical marker of organophosphate (OP) caused cardiac toxicity is long-QT syndrome (LQTS), elongation of the repolarization period in the ventricles, as measured in an electrocardiogram (ECG). The primary membrane currents responsible for this condition are two potassium currents, k/spl dot/r and i/spl dot//sub Ks/. This computer simulation investigated the effect of modulation of the cardiac membrane currents on the action potential in a two-dimensional slab of tissue affected by OP. We have shown that modulation of the sodium current and reduction of the potassium currents mimic the experimentally observed change in slope of depolarization in the presence of organophosphates as well as the prolongation and shape of repolarization, a precursor to the onset of Torsade de Pointes (TdP) and ventricular fibrillation (VF).