Novel experimental results in human cardiac electrophysiology: measurement of the Purkinje fibre action potential from the undiseased human heart

Data obtained from canine cardiac electrophysiology studies are often extrapolated to the human heart. However, it has been previously demonstrated that because of the lower density of its K+ currents, the human ventricular action potential has a less extensive repolarization reserve. Since the relevance of canine data to the human heart has not yet been fully clarified, the aim of the present study was to determine for the first time the action potentials of undiseased human Purkinje fibres (PFs) and to compare them directly with those of dog PFs. All measurements were performed at 37 °C using the conventional microelectrode technique. At a stimulation rate of 1 Hz, the plateau potential of human PFs is more positive (8.0 ± 1.8 vs 8.6 ± 3.4 mV, n = 7), while the amplitude of the spike is less pronounced. The maximal rate of depolarization is significantly lower in human PKs than in canine PFs (406.7 ± 62 vs 643 ± 36 V/s, respectively, n = 7). We assume that the appreciable difference in the protein expression profiles of the 2 species may underlie these important disparities. Therefore, caution is advised when canine PF data are extrapolated to humans, and further experiments are required to investigate the characteristics of human PF repolarization and its possible role in arrhythmogenesis.

Mathematical models of the electrical action potential of Purkinje fibre cells

Early development of ionic models for cardiac myocytes, from the pioneering modification of the Hodgkin–Huxley giant squid axon model by Noble to the iconic DiFrancesco–Noble model integrating voltage-gated ionic currents, ion pumps and exchangers, Ca 2+ sequestration and Ca 2+ -induced Ca 2+ release, provided a general description for a mammalian Purkinje fibre (PF) and the framework for modern cardiac models. In the past two decades, development has focused on tissue-specific models with an emphasis on the sino-atrial (SA) node, atria and ventricles, while the PFs have largely been neglected. However, achieving the ultimate goal of creating a virtual human heart will require detailed models of all distinctive regions of the cardiac conduction system, including the PFs, which play an important role in conducting cardiac excitation and ensuring the synchronized timing and sequencing of ventricular contraction. In this paper, we present details of our newly developed model for the human PF cell including validation against experimental data. Ionic mechanisms underlying the heterogeneity between the PF and ventricular action potentials in humans and other species are analysed. The newly developed PF cell model adds a new member to the family of human cardiac cell models developed previously for the SA node, atrial and ventricular cells, which can be incorporated into an anatomical model of the human heart with details of its electrophysiological heterogeneity and anatomical complexity.