Galappaththige Suran K, Gray Richard A, Roth Bradley J
Department of Physics, Oakland University, Rochester, Michigan, United States of America.
Center for Devices and Radiological Health, Food and Drug Administration, Silver Spring, Maryland, United States of America.
PLoS One. 2017 Feb 21;12(2):e0171144. doi: 10.1371/journal.pone.0171144. eCollection 2017.
The strength-interval curve plays a major role in understanding how cardiac tissue responds to an electrical stimulus. This complex behavior has been studied previously using the bidomain formulation incorporating the Beeler-Reuter and Luo-Rudy dynamic ionic current models. The complexity of these models renders the interpretation and extrapolation of simulation results problematic. Here we utilize a recently developed parsimonious ionic current model with only two currents-a sodium current that activates rapidly upon depolarization INa and a time-independent inwardly rectifying repolarization current IK-which reproduces many experimentally measured action potential waveforms. Bidomain tissue simulations with this ionic current model reproduce the distinctive dip in the anodal (but not cathodal) strength-interval curve. Studying model variants elucidates the necessary and sufficient physiological conditions to predict the polarity dependent dip: a voltage and time dependent INa, a nonlinear rectifying repolarization current, and bidomain tissue with unequal anisotropy ratios.
强度-间期曲线在理解心脏组织如何对电刺激作出反应方面起着重要作用。此前已使用结合了Beeler-Reuter和Luo-Rudy动态离子电流模型的双域公式对这种复杂行为进行了研究。这些模型的复杂性使得模拟结果的解释和外推存在问题。在此,我们使用了一种最近开发的简约离子电流模型,该模型仅包含两种电流——一种在去极化时迅速激活的钠电流INa和一种与时间无关的内向整流复极化电流IK——它能重现许多实验测量的动作电位波形。使用这种离子电流模型进行的双域组织模拟重现了阳极(而非阴极)强度-间期曲线中独特的凹陷。对模型变体的研究阐明了预测极性依赖性凹陷所需的充分生理条件:电压和时间依赖性的INa、非线性整流复极化电流以及各向异性比率不等的双域组织。