Proceedings of The Physiological Society

University of Oxford (2011) Proc Physiol Soc 23, PC140

Poster Communications

M Cells in Humans: Action Potential Modelling and Inpact on APD Distribution in Cardiac Tissue

G. Callisesi1, S. Kharche1,2, S. Severi1

1. Department of Electronics and Computer Science and Systems, University of Bologna, Bologna, Italy. 2. School of Physics and Astronomy, University Manchester, Manchester, United Kingdom.

  • AP profiles and AP heterogeniety in human ventricle. A: AP profiles for epi, M, TM, and endo cell types. B: AP heterogeniety in the 1D virtual strand showing AP durations with intercellular coupling (solid line) and without coupling (gray lines).

Introduction: The human ventricle has been thought to consist of epicardial (epi)and endocardial (endo) cell types. A recent experimental study [1] has confirmed the midmoycardial (M) cell type in the human ventricle, along with transitional midmyocardial (TM) cell type. M cells have markedly prolonged action potentials (APs) and distinct ionic current properties. We hypothesised that human ventricles consist of four cell types, and M along with TM contribute to tissue propagation properties. We developed mathematical models of M and the newly found TM cell types. Experimetally observed conduction patterns using a heterogeneous 1D model of virtual human ventricular tissue were reproduced in simulations. Methods: Experimental data of major ionic curents were incorporated into a recent biophysically detailed model [2] to reproduce human M and TM cell APs. In brief, a late sodium current (INaL) component was added to the sodium current (INa), the inward potassium current (IK1) conductance was reduced by 26%, and the slow rectifier potassium current (IKs) conductance was reduced by 54% to simulate M cell AP. A TM model was similarly constructed. Single cell APs were compared at different pacing cycles for the four different cell types. A 1D virtual tissue strand model incorporating electrophysiological heterogeniety was constructed based on experimental data [1]. An established computational environment, CHASTE [3], was adopted in the simulations. Cell APDs for the four cell types were computed and compared to experimentally observed APDs in various single cells at different pacing rates. The 1D strand model was used to simulate various conduction patterns. Results: The model reproduced the reported prolonged APs and rate adaptation characteristics of M cells (Fig. 1, A). The difference between M and epi repolarization is primarily due to INaL. APD restitution is steeper in M cells than in the other cell types, indicating the augmented electrical heterogenity due to M cell type. APD distribution along the 1D strand revealed the role of M cells in augmenting transmural heterogeneity (Fig. 1, B). At slow rates AP is longer in M and endocardial regions than in epicardium. M and TM cells distinctly regulated conduction patterns in the 1D strand model. Conclusions: INaL was found to be the major contributor to the prolonged M cell AP. Our 1D strand model of ventricular tissue successfully reproduces the profile of APD distribution across the ventricular wall. It is a useful tool for investigating the role of M and TM cells in ventricular conduction patterns.

Where applicable, experiments conform with Society ethical requirements