Puglisi J L, Bers D M
Department of Physiology and Biophysics, University of Illinois at Chicago, Stritch School of Medicine, Maywood, Illinois 60153, USA.
Am J Physiol Cell Physiol. 2001 Dec;281(6):C2049-60. doi: 10.1152/ajpcell.2001.281.6.C2049.
An interactive computer program, LabHEART, was developed to simulate the action potential (AP), ionic currents, and Ca handling mechanisms in a rabbit ventricular myocyte. User-oriented, its design allows switching between voltage and current clamp and easy on-line manipulation of key parameters to change the original formulation. The model reproduces normal rabbit ventricular myocyte currents, Ca transients, and APs. We also changed parameters to simulate data from heart failure (HF) myocytes, including reduced transient outward (I(to)) and inward rectifying K currents (I(K1)), enhanced Na/Ca exchange expression, and reduced sarcoplasmic reticulum Ca-ATPase function, but unaltered Ca current density. These changes caused reduced Ca transient amplitude and increased AP duration (especially at lower frequency) as observed experimentally. The model shows that the increased Na/Ca exchange current (I(NaCa)) in HF lowers the intracellular [Ca] threshold for a triggered AP from 800 to 540 nM. Similarly, the decrease in I(K1) reduces the threshold to 600 nM. Changes in I(to) have no effect. Combining enhanced Na/Ca exchange with reduced I(K1) (as in HF) lowers the threshold to trigger an AP to 380 nM. These changes reproduce experimental results in HF, where the contributions of different factors are not readily distinguishable. We conclude that the triggered APs that contribute to nonreentrant ventricular tachycardia in HF are due approximately equally (and nearly additively) to alterations in I(NaCa) and I(K1). A free copy of this software can be obtained at http://www.meddean.luc.edu/lumen/DeptWebs/physio/bers.html.
开发了一个交互式计算机程序LabHEART，用于模拟兔心室肌细胞的动作电位（AP）、离子电流和钙处理机制。该程序以用户为导向，其设计允许在电压钳和电流钳之间切换，并可轻松在线操作关键参数以改变原始配方。该模型可再现正常兔心室肌细胞电流、钙瞬变和动作电位。我们还改变参数以模拟心力衰竭（HF）心肌细胞的数据，包括瞬时外向电流（I(to)）和内向整流钾电流（I(K1)）减少、钠/钙交换表达增强以及肌浆网钙ATP酶功能降低，但钙电流密度未改变。如实验观察到的那样，这些变化导致钙瞬变幅度降低和动作电位持续时间增加（尤其是在较低频率时）。该模型表明，HF中增加的钠/钙交换电流（I(NaCa)）将触发动作电位的细胞内[Ca]阈值从800 nM降至540 nM。同样，I(K1)的降低将阈值降至600 nM。I(to)的变化没有影响。将增强的钠/钙交换与降低的I(K1)相结合（如在HF中）将触发动作电位的阈值降至380 nM。这些变化再现了HF中的实验结果，其中不同因素的贡献不易区分。我们得出结论，导致HF中非折返性室性心动过速的触发动作电位大约同等程度（且几乎呈相加性）地归因于I(NaCa)和I(K1)的改变。可在http://www.meddean.luc.edu/lumen/DeptWebs/physio/bers.html获取该软件的免费副本。
