Ionic mechanisms of variability in electrophysiological properties in Ischemia: A population-based study

Electrophysiological heterogeneities in ischemia provide a pro-arrhythmic substrate that can lead to ventricular arrhythmias. However, the mechanisms underlying intersubject variability in the pro-arrhythmic response of the human ventricles to acute ischaemia are unknown. In this initial study, we investigated the ionic basis of variability in cellular electrophysiological properties in normal and acutely ischemic human ventricular cardiomyocytes using a population-based simulation study. Additionally, we analysed the importance of hyperkalemia, I_K(ATP) activation and acidosis-induced I_CaL and I_Na inhibition in modulating these electrophysiological properties within the human cell population. Results show that in the occurrence of APD alternans, the conductance g_CaL plays the most important role followed by the Na/K pump whereas under ischemic conditions, other mechanisms also become important such as Na/Ca exchanger and the I_Kr and I_Ks currents. On the maximum restitution slope, under ischemic conditions, g_Na and g_NaCa become important while g_Kr reduce its influence on it.