A mathematical model of action potential heterogeneity in adult rat left ventricular myocytes

Mathematical models were developed to reconstruct the action potentials (AP ) recorded in epicardial and endocardial myocytes isolated from the adult r at left ventricle. The main goal was to obtain additional insight into the ionic mechanisms responsible for the transmural AP heterogeneity. The simul ation results support the hypothesis that the smaller density and the slowe r reactivation kinetics of the Ca2+-independent transient outward K+ curren t (I-t) in the endocardial myocytes can account for the longer action poten tial duration (APD), and more prominent rate dependence in that cell type. The larger density of the Na+ current (I-Na) in the endocardial myocytes re sults in a faster upstroke (dV/dt(max)). This, in addition to the smaller m agnitude of I-t, is responsible for the larger peak overshoot of the simula ted endocardial AP. The prolonged APD in the endocardial cell also leads to an enhanced amplitude of the sustained K+ current (I-ss) and a larger infl ux of Ca2+ ions via the L-type Ca2+ current (I-Cat). The latter results in an increased sarcoplasmic reticulum (SR) load, which is mainly responsible for the higher peak systolic value of the Ca2+ transient [Ca2+](i), and the resultant increase in the Na+-Ca2+ exchanger (I-NaCa) activity, associated with the simulated endocardial AP. In combination, these calculations prov ide novel, quantitative insights into the repolarization process and its na turally occurring transmural variations in the rat left ventricle.