title: Effects of elevated Homocysteine hormone on electrical activity in the human atrium: A simulation study.
abstract: Atrial fibrillation (AF) accounts for a large proportion of healthcare expenditure world wide. Mechanisms underlying the genesis and maintenance of AF are still poorly understood. Though AF is largely thought to be caused and perpetuated by dysfunctions of cellular ion channels, disrupted intercellular gap junctional electrical coupling, and/or structural changes in the atria, it is also associated with abnormal secretion of hormones, such as a high level of Homocysteine (Hcy). It was found that a high concentration Hcy induces electrical remodeling of ion channels in human atrial cells that include the ultra rapid potassium, inward rectifier potassium and transient outward potassium currents. Such Hcy-induced ion channel remodeling in repolarising potassium currents has been hypothesized to be pro-arrhythmic. In this study, we carried out multi-scale simulations to evaluate the effects of Hcy-induced changes in potassium currents on the electrical activity of human atrium at single cell, 1D strand of tissue, and 3D anatomical models. We found that high Hcy concentration produced marked changes in atrial action potentials, including a more hyperpolarized resting potential, elevated plateau potential during early stages of repolarization and abbreviated action potential duration (APD). Losses in rate dependent accommodation of APD and effective refractory period were observed. In the tissue models, high Hcy concentration slowed down atrial excitation conduction at low rates, but facilitated it at high rates. Simulated re-entrant scroll waves in the 3D model self-terminated under Control condition, but sustained under high Hcy condition. These results collectively demonstrate the pro-arrhythmic effects of a high level Hcy in promoting and sustaining AF.
authors: University of Manchester, UK. Phillip.Law@postgrad.manchester.ac.uk
authors: Phillip
authors: P
authors: Law
authors: Sanjay
authors: S
authors: Kharche
authors: Jonathan
authors: J
authors: Stott
authors: Henggui
authors: H
authors: Zhang
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000465:Algorithms; D001145:Arrhythmias, Cardiac / Q000097:blood / Q000473:pathology*; D001281:Atrial Fibrillation / Q000503:physiopathology; D001703:Biophysics / Q000379:methods*; D003198:Computer Simulation; D004553:Electric Conductivity; D004594:Electrophysiology / Q000379:methods*; D017629:Gap Junctions; D006325:Heart Atria / Q000473:pathology*; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008953:Models, Anatomic; D015221:Potassium Channels / Q000378:metabolism; D013997:Time Factors
chemical_list: D015221:Potassium Channels; D006710:Homocysteine