Role of the Late Sodium Current in Rate-Dependent Repolarization of the Canine Ventricle

Late sodium current I(NaL) is an inward current participating in maintaining the plateau of the action potential. So far its role in the repolarization of canine hearts is not well known. In this paper, by taking advantage of a computer simulation method, we developed a one-dimensional transmural tissue to study the impacts of I(NaL) on rate-dependent repolarization and its ionic basis in the canine ventricle. An OpenMP parallel algorithm was performed on a four-core personal computer to accelerate the simulation. The results demonstrated that action potential durations of midmyocytes showed greater rate dependence than the endo- and epi-myocytes. When the pacing rate was reduced, repolarization of the tissue was prolonged while the transmural dispersion of repolarization (TDR) was enlarged. The enhancement of I(NaL) further amplified this rate-dependent repolarization and TDR meanwhile increased the risk of arrhythmogenesis. I(NaL) was found highly sensitive to the pacing rate by calculating its kinetics. The study suggested that I(NaL) played an important role in the rate-dependent repolarization of the canine ventricle. Selective blockade of I(NaL) could have clinical benefits, especially for such pathological conditions with enhanced I(NaL) as long QT 3 syndrome and heart failure.