Faville R A, Pullan A J, Sanders K M, Smith N P
The Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand.
Biophys J. 2008 Jul;95(1):88-104. doi: 10.1529/biophysj.107.122507. Epub 2008 Mar 13.
Unitary potential (UP) depolarizations are the basic intracellular events responsible for pacemaker activity in interstitial cells of Cajal (ICCs), and are generated at intracellular sites termed "pacemaker units". In this study, we present a mathematical model of the transmembrane ion flows and intracellular Ca(2+) dynamics from a single ICC pacemaker unit acting at near-resting membrane potential. This model quantitatively formalizes the framework of a novel ICC pacemaking mechanism that has recently been proposed. Model simulations produce spontaneously rhythmic UP depolarizations with an amplitude of approximately 3 mV at a frequency of 0.05 Hz. The model predicts that the main inward currents, carried by a Ca(2+)-inhibited nonselective cation conductance, are activated by depletion of sub-plasma-membrane [Ca(2+)] caused by sarcoendoplasmic reticulum calcium ATPase Ca(2+) sequestration. Furthermore, pacemaker activity predicted by our model persists under simulated voltage clamp and is independent of [IP(3)] oscillations. The model presented here provides a basis to quantitatively analyze UP depolarizations and the biophysical mechanisms underlying their production.
单一电位（UP）去极化是负责 Cajal 间质细胞（ICC）起搏活动的基本细胞内事件，由称为“起搏单元”的细胞内位点产生。在本研究中，我们提出了一个数学模型，该模型描述了单个 ICC 起搏单元在接近静息膜电位时的跨膜离子流和细胞内 Ca(2+)动力学。该模型定量地形式化了最近提出的一种新型 ICC 起搏机制的框架。模型模拟产生了自发节律性的 UP 去极化，其幅度约为 3 mV，频率为 0.05 Hz。该模型预测，由 Ca(2+)抑制的非选择性阳离子电导携带的主要内向电流，由肌浆网钙 ATP 酶 Ca(2+)螯合导致的亚细胞膜[Ca(2+)]耗竭激活。此外，我们模型预测的起搏活动在模拟电压钳制下持续存在，并且与[IP(3)]振荡无关。这里提出的模型为定量分析 UP 去极化及其产生的生物物理机制提供了基础。
