Biosimulation Project, Faculty of Bioinformatics, Ritsumeikan University, Kusatsu City, Japan.
Biophys J. 2009 Dec 16;97(12):3086-94. doi: 10.1016/j.bpj.2009.08.060.
The action potential, once triggered in ventricular or atrial myocytes, automatically proceeds on its time course or is generated spontaneously in sinoatrial node pacemaker cells. It is induced by complex interactions among such cellular components as ion channels, transporters, intracellular ion concentrations, and signaling molecules. We have developed what is, to our knowledge, a new method using a mathematical model to quantify the contribution of each cellular component to the automatic time courses of the action potential. In this method, an equilibrium value, which the membrane potential is approaching at a given moment, is calculated along the time course of the membrane potential. The calculation itself is based on the time-varying conductance and the reversal potentials of individual ion channels and electrogenic ion transporters. Since the equilibrium potential moves in advance of the membrane potential change, we refer to it as the lead potential, V(L). The contribution of an individual current was successfully quantified by comparing dV(L)/dt before and after fixing the time-dependent change of a component of interest, such as the variations in the open probability of a channel or the turnover rate of an ion transporter. In addition to the action potential, the lead-potential analysis should also be applicable in all types of membrane excitation in many different kinds of cells.
动作电位一旦在心室或心房肌细胞中被触发，就会自动沿着时间进程进行，或者在窦房结起搏细胞中自发产生。它是由离子通道、转运体、细胞内离子浓度和信号分子等细胞成分之间的复杂相互作用诱导的。我们开发了一种新方法，使用数学模型来定量评估每个细胞成分对动作电位自动时间进程的贡献。在这种方法中，沿着膜电位的时间进程计算出在给定时刻膜电位接近的平衡值。该计算基于单个离子通道和产生电的离子转运体的时变电导和反转电位。由于平衡电位先于膜电位变化移动，因此我们将其称为先导电位 V(L)。通过比较感兴趣的组件（例如通道的开放概率或离子转运体的周转率的变化）的时间依赖性变化前后的 dV(L)/dt，可以成功地量化单个电流的贡献。除了动作电位之外，这种先导电位分析也应该适用于许多不同类型的细胞中的所有类型的膜兴奋。
