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.