A mathematical model of a bullfrog cardiac pacemaker cell.
A mathematical model of a bullfrog cardiac pacemaker cell.
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牛蛙心脏起搏器细胞的数学模型。
DOI：
10.1152/ajpheart.1990.259.2.h352
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发表时间：
1990
期刊：
影响因子：
--
通讯作者：
Campbell,DL
中科院分区：
文献类型：
--
作者：
Rasmusson,RL;Clark,JW;Giles,WR;Shibata,EF;Campbell,DL
先前的心脏细胞电生理学模型主要基于从多细胞制备物获得的电压钳测量，并且通常结合来自心脏不同区域和各种物种的数据。我们已经开发了一个模型的心脏起搏的基础上，从一个特定的组织类型，牛蛙静脉窦（SV）分离的单细胞获得的电压钳测量的全面设置。因此，肌膜电流密度和动力学不受与多细胞制剂相关的次级现象的影响，使我们能够真实地模拟被认为在起搏中重要的过程，包括Na（+）-K+泵和Na（+）-Ca 2+交换器。膜在细胞外被扩散限制空间包围，在细胞内被含有Ca 2（+）结合蛋白（钙调蛋白、肌钙蛋白）的有限肌浆体积包围。该模型对起搏所涉及的机制做出了几项预测。1)初级起搏不能归因于任何单一电流，而是由于缺乏背景K+电流以及Ca 2+、延迟整流K+和背景漏电流之间的复杂相互作用引起的。2)Ca 2+电流表现出复杂的行为，在复极过程中是重要的。3)由于肌浆蛋白对Ca ~（2+）的缓冲作用，Na（+）-Ca ~（2+）交换器电流较小，对动作电位复极影响不大，但可调节最大舒张电位。4)Na（+）-K+泵电流在复极化中不起积极作用，但其大小足以调节舒张期去极化的速率。5)K+蓄积和Ca ~（2+）耗竭可能发生在细胞外间隙，但在单个动作电位的舒张期去极化或复极中不起作用。该模型说明了基于定量测量的离子电流在肌细胞中的模拟，包括两个生电转运机制和钙缓冲肌浆钙（+）结合蛋白的重要性。
Previous models of cardiac cellular electrophysiology have been based largely on voltage-clamp measurements obtained from multicellular preparations and often combined data from different regions of the heart and a variety of species. We have developed a model of cardiac pacemaking based on a comprehensive set of voltage-clamp measurements obtained from single cells isolated from one specific tissue type, the bullfrog sinus venosus (SV). Consequently, sarcolemmal current densities and kinetics are not influenced by secondary phenomena associated with multicellular preparations, allowing us to realistically simulate processes thought to be important in pacemaking, including the Na(+)-K+ pump and Na(+)-Ca2+ exchanger. The membrane is surrounded extracellularly by a diffusion-limited space and intracellularly by a limited myoplasmic volume containing Ca2(+)-binding proteins (calmodulin, troponin). The model makes several predictions regarding mechanisms involved in pacing. 1) Primary pacemaking cannot be attributed to any single current but arises from both the lack of a background K+ current and a complex interaction between Ca2+, delayed-rectifier K+, and background leak currents. 2) Ca2+ current displays complex behavior and is important during repolarization. 3) Because of Ca2+ buffering by myoplasmic proteins, the Na(+)-Ca2+ exchanger current is small and has little influence on action potential repolarization but may modulate the maximum diastolic potential. 4) The Na(+)-K+ pump current does not play an active role in repolarization but is of sufficient size to modulate the rate of diastolic depolarization. 5) K+ accumulation and Ca2+ depletion may occur in the extracellular spaces but play no role in either the diastolic depolarization or repolarization of a single action potential. This model illustrates the importance of basing simulations on quantitative measurements of ionic currents in myocytes and of including both electrogenic transporter mechanisms and Ca2+ buffering by myoplasmic Ca2(+)-binding proteins.