ELECTRICAL AND CHEMICAL OSCILLATIONS IN COUPLED CELL SYSTEMS

耦合电池系统中的电振荡和化学振荡

• 批准号: 6432053
• 负责人: Arthur Stewart Sherman
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6432053
• 关键词: biophysics; cell cell interaction; electrophysiology; insulin; intracellular; mathematical model; membrane activity; membrane channels; membrane model; membrane potentials; model design /development; neurons; pancreatic islet function; pancreatic islets; secretion

We use mathematical models to study the mechanisms of oscillatory electrical activity arising from ion channels in cell membranes and modulated by intracellular chemical processes. We are interested in both the behavior of single cells and the ways in which cells communicate and modify each other's behavior. Our main application has been to the biophysical basis of insulin secretion in pancreatic beta-cells. We have examined bursting oscillations in membrane potential and the role of electrical coupling between cells in the islet of Langerhans. Long term goals are to understand how the membrane dynamics interact with intracellular events to regulate secretion. We also compare, contrast, and generalize to other secretory cells and neurons, including GnRH-secreting hypothalamic neurons, pituitary somatotrophs, and fast neurotransmitter secretion at nerve terminals. Our primary tool is the numerical solution of ordinary and partial differential equations. We use analytical, geometrical, graphical, and numerical techniques from the mathematical theory of dynamical systems to help construct and interpret the models. Perturbation techniques are used to get analytical results in special cases. We study both detailed biophysical models and simplified models which are more amenable to analysis. Such an approach aids the isolation of the essential or minimal mechanisms underlying phenomena, the search for general principles, and the application of concepts and analogies from other fields. We see a role for our group as intermediaries between the mathematical and biological disciplines. This includes disseminating the insights of mathematical work to biologists in accessible language and alerting mathematicians and other theoreticians to new and challenging problems arising from biological issues.

我们使用数学模型来研究细胞膜上离子通道产生并受细胞内化学过程调制的振荡电活动的机制。我们既对单个细胞的行为感兴趣，也对细胞之间的交流和改变彼此行为的方式感兴趣。我们的主要应用是研究胰岛β细胞分泌胰岛素的生物物理基础。我们研究了朗格汉斯胰岛细胞膜电位的爆发性振荡和细胞间电耦合的作用。长期目标是了解膜动力学如何与细胞内事件相互作用来调节分泌。我们还比较、对比和推广到其他分泌细胞和神经元，包括分泌GnRH的下丘脑神经元、垂体生长激素和神经末梢的快速神经递质分泌。我们的主要工具是常微分方程组和偏微分方程组的数值解。我们使用动力系统数学理论中的分析、几何、图形和数值技术来帮助构建和解释模型。在特殊情况下，采用摄动法得到分析结果。我们既研究详细的生物物理模型，也研究更易于分析的简化模型。这种方法有助于隔离现象背后的基本或最小机制，寻找一般原理，并应用其他领域的概念和类比。我们认为我们的团队将扮演数学和生物学科之间的中间人的角色。这包括用通俗易懂的语言向生物学家传播数学工作的见解，并提醒数学家和其他理论家注意生物学问题产生的新的和具有挑战性的问题。