Modelling Electrical Bursting and Calcium Waves in Pancreatic beta-Cells

模拟胰腺 β 细胞中的电爆发和钙波

• 批准号: 9411244
• 负责人: Teresa Chay
• 金额: $ 10.5万
• 依托单位: University of Pittsburgh
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-09-01 至 1999-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9411244&HistoricalAwards=false
• 关键词: Modelling; Electrical; Bursting; Calcium; Waves

9411244 Chay In pancreatic beta cells the ion channels, the phosphatidylinositol signal, and the receptor controlled adenylate-cyclase pathway are intricately interwoven so as to control insulin release. Modelling studies will certainly help clarify the main events that take place in these complex interwoven phenomena. The goal of this research is to formulate a mathematical model that explains the interplay between the ion channels, receptors, intracellular calcium stores, and intercellular calcium wave propagation in pancreatic beta-cells in the islet of Langerhans. This project has two major goals. The first is to incorporate recent patch-clamp experiments and spectrophotometric data into the mathematical bursting model developed by this group over a number of years so as to link the membrane oscillator model with a receptor-controlled calcium oscillator model. With this refined model, the role each channel plays in triggering the bursting and intracellular calcium oscillations will be quantified, and the coordination of release of calcium from internal stores with the influx of extracellular calcium will be investigated. In addition, how electrical activity and intracellular calcium concentration change in response to intra-islet hormones and neurotransmitters released from sympathetic and parasympathetic fibers will be explored. The second major goal is to develop user-friendly software which simulates beta cell electrophysiology and intracellular calcium dynamics for researchers studying excitable cells as well as for teachers in the classroom. %%% Insulin is a hormone that plays a key role in regulating the level of sugar in blood. Insulin is produced in specialized cells of the pancreas, the beta cells. Beta cells release insulin in response to a number of external stimuli such as increases in the blood concentration of the simple sugar, glucose, as well as certain neurotransmitters and some other hormones. Understanding the chain of events between the cell's detection of these chemical stimuli and the release of insulin is the goal of much research in many laboratories. It is known that the chain of events involves bursts of electrical activity at the beta cell membrane and oscillations of the cell's internal calcium levels. Each of these is caused by certain biochemical changes in the cell and results in other biochemical changes. The goal of this research is to develop detailed mathematical models that will aid in clarifying the relationships among these complex and interdependent sequences of biochemical and biophysical events. Mathematical models are useful not only in helping to interpret existing experimental data but also in suggesting further experiments that ultimately will allow us to understand the transduction of the extracellular signals that stimulate pancreatic cells to release insulin. A second goal of this project is to develop user-friendly software that will facilitate studies by other researchers and students interested in similar biophysical and biochemical phenomena. ***

小行星9411244 在胰腺β细胞中，离子通道、磷脂酰肌醇信号和受体控制的腺苷酸环化酶途径错综复杂地交织在一起，从而控制胰岛素释放。 模型研究肯定有助于澄清在这些复杂的相互交织的现象中发生的主要事件。 本研究的目的是制定一个数学模型，解释离子通道，受体，细胞内钙储存，和细胞间钙波传播在胰岛β细胞的胰岛之间的相互作用。 该项目有两个主要目标。 第一个是将最近的膜片钳实验和分光光度计的数据到由这个小组开发了数年的数学爆发模型，以便连接膜振荡器模型与受体控制的钙振荡器模型。 有了这个完善的模型，每个通道在触发爆裂和细胞内钙振荡中发挥的作用将被量化，并将研究从内部存储的钙释放与细胞外钙的流入的协调。 此外，如何电活动和细胞内钙浓度的变化，响应胰岛内的激素和神经递质释放的交感神经和副交感神经纤维将被探讨。 第二个主要目标是开发用户友好的软件，模拟β细胞电生理学和细胞内钙动力学的研究人员研究兴奋细胞以及教师在课堂上。 %%% 胰岛素是一种在调节血糖水平方面起关键作用的激素。 胰岛素是在胰腺的特殊细胞中产生的，即β细胞。 β细胞释放胰岛素以响应许多外部刺激，例如简单糖、葡萄糖以及某些神经递质和一些其他激素的血液浓度的增加。 了解细胞对这些化学刺激的检测和胰岛素的释放之间的事件链是许多实验室的许多研究的目标。 众所周知，这一系列事件涉及β细胞膜上的电活动爆发和细胞内部钙水平的振荡。 每一种都是由细胞中的某些生化变化引起的，并导致其他生化变化。 这项研究的目标是开发详细的数学模型，将有助于澄清这些复杂的和相互依存的序列的生物化学和生物物理事件之间的关系。 数学模型不仅有助于解释现有的实验数据，而且有助于提出进一步的实验，最终使我们能够理解刺激胰腺细胞释放胰岛素的细胞外信号的转导。 该项目的第二个目标是开发方便用户的软件，以便利对类似生物物理和生物化学现象感兴趣的其他研究人员和学生的研究。 ***