J M Meunier1, N A Trayanova, R A Gray. 1. Department of Biomedical Engineering, Tulane University, New Orleans, Louisiana 70118-5674, USA. meunier@elwood.bmen.tulane.edu
Abstract
INTRODUCTION: Cardiac tissue subjected to sinusoidal stimulus is characterized by action potentials (APs) that have extended plateau phases, sustained for the duration of the stimulus. Extended action potential durations (APDs) are beneficial because they disrupt wandering wavelets in the fibrillating heart. To investigate the mechanisms by which periodic stimulus affects cardiac tissue, particularly the development of sustained depolarization, computer simulations of single cardiac cells exposed to alternating current (AC) are performed. METHODS AND RESULTS: Two modes of stimulation of the cell are examined: external field stimulation and transmembrane current injection. Several membrane models, including Luo-Rudy I and II, are used in the simulations. External AC field stimuli increase the APD of the single cell. The extended plateau of the cellular AP is characterized by periodic oscillations that are 1:2 phase locked with the applied stimulus. This specific behavior is due to the variations in stimulus magnitude and polarity along the cell border, which elicit opposite electrical responses from the cell sides. These pointwise responses are averaged in the macroscopic cellular response and result in sustained oscillatory depolarization that lasts for the duration of the stimulus. In contrast, the cell undergoing current injection does not develop an extended APD. CONCLUSION: The simulations demonstrate that variation of membrane potential within a cell is of paramount importance to the formation of an extended AP plateau in response to AC stimulation.
INTRODUCTION: Cardiac tissue subjected to sinusoidal stimulus is characterized by action potentials (APs) that have extended plateau phases, sustained for the duration of the stimulus. Extended action potential durations (APDs) are beneficial because they disrupt wandering wavelets in the fibrillating heart. To investigate the mechanisms by which periodic stimulus affects cardiac tissue, particularly the development of sustained depolarization, computer simulations of single cardiac cells exposed to alternating current (AC) are performed. METHODS AND RESULTS: Two modes of stimulation of the cell are examined: external field stimulation and transmembrane current injection. Several membrane models, including Luo-Rudy I and II, are used in the simulations. External AC field stimuli increase the APD of the single cell. The extended plateau of the cellular AP is characterized by periodic oscillations that are 1:2 phase locked with the applied stimulus. This specific behavior is due to the variations in stimulus magnitude and polarity along the cell border, which elicit opposite electrical responses from the cell sides. These pointwise responses are averaged in the macroscopic cellular response and result in sustained oscillatory depolarization that lasts for the duration of the stimulus. In contrast, the cell undergoing current injection does not develop an extended APD. CONCLUSION: The simulations demonstrate that variation of membrane potential within a cell is of paramount importance to the formation of an extended AP plateau in response to AC stimulation.
Authors: Harikrishna Tandri; Seth H Weinberg; Kelly C Chang; Renjun Zhu; Natalia A Trayanova; Leslie Tung; Ronald D Berger Journal: Sci Transl Med Date: 2011-09-28 Impact factor: 17.956