Warashina A, Ogura T
Division of Cell Physiology, Niigata University Graduate School of Medical and Dental Sciences, 951-8510, Niigata, Japan.
Pflugers Arch. 2004 May;448(2):161-74. doi: 10.1007/s00424-003-1169-x. Epub 2004 Jan 17.
We constructed a chromaffin cell model for analysis of stimulation-secretion coupling in computer simulation studies. The model includes mechanisms involved in the excitatory synapse, voltage-dependent Na(+), K(+) and Ca(2+) channels, Ca(2+)-activated K(+) channels (SK type), buffered Ca(2+) diffusion, Ca(2+) extrusion, fluorescent Ca(2+) indicators and Ca(2+)-triggered exocytosis. Calculations of the modeled mechanisms were carried out using the NEURON simulation environment (Hines and Carnevale, Neural Computation 9:1179-1209, 1997). A set of parameter values was determined so as to fit basic experimental results reported in the literature. The model was also applied to simulate our experimental results obtained from chromaffin cells in the perfused rat adrenal medulla. Observed profiles of Ca(2+)responses induced by electrically stimulating the splanchnic nerve with various frequencies (1-50 Hz) were adequately simulated with minor readjustments of parameter values for Ca(2+)influx and extrusion. Secretory responses measured at the same time as the Ca(2+)responses were also simulated with consideration of a time constant to detect catecholamines in the experiment. Similarly, model simulations reproduced both Ca(2+)responses and secretory responses evoked by elevations of the extracellular K(+) concentration for different periods. The results suggest that the presented model provides a useful tool for analyzing and predicting quantitative relations in various events occurring in stimulation-secretion coupling in chromaffin cells.
我们构建了一个嗜铬细胞模型，用于在计算机模拟研究中分析刺激-分泌偶联。该模型包括兴奋性突触、电压依赖性钠（Na⁺）、钾（K⁺）和钙（Ca²⁺）通道、钙激活钾（K⁺）通道（SK型）、缓冲钙（Ca²⁺）扩散、钙（Ca²⁺）外排、荧光钙（Ca²⁺）指示剂以及钙（Ca²⁺）触发的胞吐作用等相关机制。使用NEURON模拟环境（Hines和Carnevale，《神经计算》9：1179 - 1209，1997）对模型机制进行计算。确定了一组参数值，以拟合文献中报道的基本实验结果。该模型还被用于模拟我们从灌注大鼠肾上腺髓质中的嗜铬细胞获得的实验结果。通过对钙（Ca²⁺）内流和外排的参数值进行微小调整，充分模拟了用不同频率（1 - 50 Hz）电刺激内脏神经所诱导的钙（Ca²⁺）反应的观察曲线。在实验中，还考虑了检测儿茶酚胺的时间常数，对与钙（Ca²⁺）反应同时测量的分泌反应进行了模拟。同样，模型模拟再现了不同时间段细胞外钾（K⁺）浓度升高所诱发的钙（Ca²⁺）反应和分泌反应。结果表明，所提出的模型为分析和预测嗜铬细胞刺激-分泌偶联中发生的各种事件的定量关系提供了一个有用的工具。
