Leem Chae Hun, Kim Won Tae, Ha Jeong Mi, Lee Yoon Jin, Seong Hyeon Chan, Choe Han, Jang Yeon Jin, Youm Jae Boum, Earm Yung E
Department of Physiology, University of Ulsan College of Medicine, 388-1 Poongnap-Dong Songpa-Ku, Seoul 138-736, South Korea.
Philos Trans A Math Phys Eng Sci. 2006 May 15;364(1842):1223-43. doi: 10.1098/rsta.2006.1766.
In recent studies, we recorded transiently activated outward currents by the application of three-step voltage pulses to induce a reverse mode of Na+-Ca2+ exchange (NCX). We found that these currents were mediated by a Ca2+-activated Cl- current. Based on the recent reports describing the atrial Ca2+ transients, the Ca2+ transient at the subsarcolemmal space was initiated and then diffused into the cytosolic space. Because the myocardium in the pulmonary vein is an extension of the atrium, the Ca2+-activated Cl- current may reflect the subsarcolemmal Ca2+ dynamics. We tried to predict the subsarcolemmal Ca2+ dynamics by simulating these current traces. According to recent reports on the geometry of atrial myocytes, we assumed that there were three compartments of sarcoplasmic reticulum (SR): a network SR, a junctional SR and a central SR. Based on these structures, we also divided the cytosolic space into three compartments: the junctional, subsarcolemmal and cytosolic spaces. Geometry information and cellular capacitance suggested that there were essentially no T-tubules in these cells. The basic physical data, such as the compartmental volumes, the diffusion coefficients and the stability coefficients of the Ca2+ buffers, were obtained from the literature. In the simulation, we incorporated the NCX, the L-type Ca2+ channel, the rapid activating outward rectifier K+ channel, the Na+-K+ pump, the SR Ca2+-pump, the ryanodine receptor, the Ca2+-activated Cl- channel and the dynamics of Na+, K+, Ca2+ and Cl-. In these conditions, we could successfully reconstruct the Ca2+-activated Cl- currents. The simulation allowed estimation of the Ca2+ dynamics of each compartment and the distribution of the Ca2+-activated Cl- channel and the NCX in the sarcolemma on the junctional or subsarcolemmal space.
在最近的研究中，我们通过施加三步电压脉冲以诱导钠钙交换（NCX）的反向模式，记录了瞬时激活的外向电流。我们发现这些电流由钙激活氯电流介导。基于最近描述心房钙瞬变的报告，肌膜下空间的钙瞬变首先启动，然后扩散到细胞质空间。由于肺静脉中的心肌是心房的延伸，钙激活氯电流可能反映了肌膜下钙动力学。我们试图通过模拟这些电流轨迹来预测肌膜下钙动力学。根据最近关于心房肌细胞几何结构的报告，我们假设肌浆网（SR）有三个区室：网络SR、连接SR和中央SR。基于这些结构，我们还将细胞质空间分为三个区室：连接区、肌膜下区和细胞质区。几何信息和细胞电容表明这些细胞中基本没有横管。诸如区室体积、扩散系数和钙缓冲剂的稳定系数等基本物理数据均从文献中获取。在模拟中，我们纳入了NCX、L型钙通道、快速激活外向整流钾通道、钠钾泵、SR钙泵、兰尼碱受体、钙激活氯通道以及钠、钾、钙和氯的动力学。在这些条件下，我们能够成功重建钙激活氯电流。该模拟能够估计每个区室的钙动力学以及连接区或肌膜下空间肌膜上钙激活氯通道和NCX的分布。
