Biosimulation Project, Faculty of Bioinformatics, Ritsumeikan University, Noji Higashi 1-1-1, Kusatsu-City, Shiga-Prefecture 525-8577, Japan.
Prog Biophys Mol Biol. 2011 Nov;107(2):265-73. doi: 10.1016/j.pbiomolbio.2011.08.001. Epub 2011 Aug 7.
Bursts of repetitive action potentials are closely related to the regulation of glucose-induced insulin secretion in pancreatic β cells. Mathematical studies with simple β-cell models have established the central principle that the burst-interburst events are generated by the interaction between fast membrane excitation and slow cytosolic components. Recently, a number of detailed models have been developed to simulate more realistic β cell activity based on expanded findings on biophysical characteristics of cellular components. However, their complex structures hinder our intuitive understanding of the underlying mechanisms, and it is becoming more difficult to dissect the role of a specific component out of the complex network. We have recently developed a new detailed model by incorporating most of ion channels and transporters recorded experimentally (the Cha-Noma model), yet the model satisfies the charge conservation law and reversible responses to physiological stimuli. Here, we review the mechanisms underlying bursting activity by applying mathematical analysis tools to representative simple and detailed models. These analyses include time-based simulation, bifurcation analysis and lead potential analysis. In addition, we introduce a new steady-state I-V (ssI-V) curve analysis. We also discuss differences in electrical signals recorded from isolated single cells or from cells maintaining electrical connections within multi-cell preparations. Towards this end, we perform simulations with our detailed pancreatic β-cell model.
脉冲串式动作电位的爆发与胰腺β细胞中葡萄糖诱导的胰岛素分泌的调节密切相关。利用简单的β细胞模型进行的数学研究确立了一个核心原则，即爆发-间歇事件是由快速膜激发和缓慢胞质成分之间的相互作用产生的。最近，根据对细胞成分的生物物理特性的扩展发现，已经开发出了许多详细的模型，以模拟更真实的β细胞活动。然而，它们复杂的结构阻碍了我们对潜在机制的直观理解，而且越来越难以从复杂的网络中分离出特定组件的作用。我们最近通过整合大多数实验记录的离子通道和转运体（Cha-Noma 模型）开发了一个新的详细模型，但该模型满足电荷守恒定律和对生理刺激的可逆响应。在这里，我们通过应用数学分析工具来分析代表性的简单和详细模型，来研究爆发活动的机制。这些分析包括基于时间的模拟、分岔分析和先导电位分析。此外，我们还引入了一种新的稳态 I-V（ssI-V）曲线分析。我们还讨论了从分离的单个细胞或在多细胞制剂中保持电连接的细胞中记录的电信号之间的差异。为此，我们使用我们的详细胰腺β细胞模型进行模拟。
