LabHEART: an interactive computer model of rabbit ventricular myocyte ion channels and Ca transport
LabHEART: an interactive computer model of rabbit ventricular myocyte ion channels and Ca transport
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DOI：
10.1152/ajpcell.2001.281.6.c2049
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发表时间：
2001-12-01
影响因子：
5.5
通讯作者：
Bers, DM
中科院分区：
文献类型：
--
作者：
Puglisi, JL;Bers, DM
本文介绍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。其设计以用户为导向，允许在电压和电流钳之间切换，并轻松在线操作关键参数以改变原始配方。该模型再现正常兔心室肌细胞电流，钙瞬变，和AP。我们还改变了参数来模拟心力衰竭（HF）心肌细胞的数据，包括瞬时外向（I-to）和内向整流钾电流（I-K1）减少，Na/Ca交换表达增强，肌浆网Ca-ATP酶功能降低，但Ca电流密度不变。这些变化导致实验观察到的钙瞬变幅度降低和AP持续时间增加（特别是在较低频率下）。该模型表明，HF中增加的Na/Ca交换电流（I-NaCa）将触发AP的细胞内[Ca]阈值从800 nM降低到540 nM。类似地，I-K1的降低将阈值降低至600 nM。I-to的变化没有影响。结合增强的Na/Ca交换和降低的I-K1（如HF），将触发AP的阈值降低至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容易区分。我们的结论是，触发AP，导致非折返性室性心动过速在HF是由于大约相等（和几乎相加）的I-NaCa和I-K1的改变。
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.