Rasmusson R L, Clark J W, Giles W R, Robinson K, Clark R B, Shibata E F, Campbell D L
Department of Electrical and Computer Engineering, Rice University, Houston, Texas 77251-1892.
Am J Physiol. 1990 Aug;259(2 Pt 2):H370-89. doi: 10.1152/ajpheart.1990.259.2.H370.
We have developed a model of cardiac atrial electrical activity based on voltage-clamp measurements obtained from single cells isolated from the bullfrog atrium. These measurements have allowed us to simulate a number of processes thought to be important in action potential initiation, repolarization, and the excitation-contraction (EC) coupling process. In this atrial model, the cell membrane contains both channel-mediated (Na+, Ca2+, inward rectifier K+, delayed rectifier K+, linear background leak) and transporter-mediated (Na(+)-K+ pump, Na(+)-Ca2+ exchanger, Ca2+ pump) currents. The cell is surrounded extracellularly by a diffusion-limited space. The intracellular volume contains Ca2(+)-binding proteins (calmodulin, troponin). The model makes several important predictions. 1) Incomplete inactivation of the Ca2+ current provides an inward current the maintains the plateau of the action potential. 2) Activation of the delayed rectifier K+ current initiates repolarization. 3) Due to Ca2+ buffering by myoplasmic proteins the Na(+)-Ca2+ exchanger current is relatively small and has little influence on repolarization. 4) The Na(+)-K+ pump current does not play a major role in repolarization. 5) K+ accumulation and Ca2+ depletion may occur in the extracellular spaces. 6) Modulation of EC coupling is governed by interactions between the myoplasmic Ca2(+)-binding proteins; specifically, the inotropic "positive staircase effect" may be explained by interactions between Ca2+ and Mg2+ at a competitive binding site on troponin. When considered in conjunction with the results of our model of primary pacemaking in the sinus venosus [Rasmusson et al., Am. J. Physiol. 259 (Heart Circ. Physiol. 28): H352-H369, 1990], this atrial model shows how the presence or absence of certain transmembrane currents can change action potential characteristics and consequently alter the relative influence of the various transporter-mediated and channel-mediated currents.
我们基于从牛蛙心房分离出的单细胞电压钳测量结果，开发了一种心脏心房电活动模型。这些测量使我们能够模拟许多在动作电位起始、复极化以及兴奋 - 收缩（EC）偶联过程中被认为很重要的过程。在这个心房模型中，细胞膜包含通道介导的电流（Na⁺、Ca²⁺、内向整流K⁺、延迟整流K⁺、线性背景泄漏电流）和转运体介导的电流（Na⁺ - K⁺泵、Na⁺ - Ca²⁺交换体、Ca²⁺泵电流）。细胞在细胞外被一个扩散受限的空间所包围。细胞内体积包含Ca²⁺结合蛋白（钙调蛋白、肌钙蛋白）。该模型做出了几个重要预测。1）Ca²⁺电流的不完全失活提供了一个内向电流，维持动作电位的平台期。2）延迟整流K⁺电流的激活引发复极化。3）由于肌浆蛋白对Ca²⁺的缓冲作用，Na⁺ - Ca²⁺交换体电流相对较小，对复极化影响不大。4）Na⁺ - K⁺泵电流在复极化中不起主要作用。5）细胞外空间可能发生K⁺积累和Ca²⁺耗竭。6）EC偶联的调节由肌浆Ca²⁺结合蛋白之间的相互作用控制；具体而言，变力性“正阶梯效应”可以通过Ca²⁺和Mg²⁺在肌钙蛋白上的竞争性结合位点之间的相互作用来解释。当结合我们在静脉窦初级起搏模型的结果考虑时[拉斯穆森等人，《美国生理学杂志》259（心脏循环生理学28）：H352 - H369，1990]，这个心房模型展示了某些跨膜电流的存在或缺失如何改变动作电位特征，进而改变各种转运体介导和通道介导电流的相对影响。
