Calcium and glycolysis mediate multiple bursting modes in pancreatic islets
Calcium and glycolysis mediate multiple bursting modes in pancreatic islets
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DOI：
10.1529/biophysj.104.049262
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发表时间：
2004-11-01
影响因子：
3.4
通讯作者：
Sherman, A
中科院分区：
文献类型：
--
作者：
Bertram, R;Satin, L;Sherman, A
当暴露于刺激性葡萄糖水平时，胰岛产生电活动的爆发。这些爆发通常具有规则的重复模式，周期为10-60 s。然而，在某些情况下，爆发是偶发的，聚集成爆发的爆发，我们称之为复合爆发。与此一致的是记录游离Ca 2+浓度、耗氧量、线粒体膜电位和胰岛内葡萄糖水平，其表现出非常缓慢的振荡，叠加有更快的振荡。我们描述了一个新的数学模型，胰腺β细胞，可以占这些多模态模式。该模型包括反馈到离子通道的胞质Ca 2+，可以占爆裂，和代谢子系统，能够产生缓慢的振荡驱动的振荡糖酵解。这种缓慢的节律是模型中化合物爆发的缓慢模式的原因。我们还表明，糖酵解振荡单独驱动一种非常缓慢的爆发形式是可能的，我们称之为“糖酵解爆发”。最后，该模型预测，在一系列参数值下，稳态和振荡糖酵解之间存在双稳态。我们为这个模型的预测提供了实验支持。总体而言，该模型可以解释过去20年文献中描述的胰岛行为的多样性。
Pancreatic islets of Langerhans produce bursts of electrical activity when exposed to stimulatory glucose levels. These bursts often have a regular repeating pattern, with a period of 10-60 s. In some cases, however, the bursts are episodic, clustered into bursts of bursts, which we call compound bursting. Consistent with this are recordings of free Ca2+ concentration, oxygen consumption, mitochondrial membrane potential, and intraislet glucose levels that exhibit very slow oscillations, with faster oscillations superimposed. We describe a new mathematical model of the pancreatic beta-cell that can account for these multimodal patterns. The model includes the feedback of cytosolic Ca2+ onto ion channels that can account for bursting, and a metabolic subsystem that is capable of producing slow oscillations driven by oscillations in glycolysis. This slow rhythm is responsible for the slow mode of compound bursting in the model. We also show that it is possible for glycolytic oscillations alone to drive a very slow form of bursting, which we call "glycolytic bursting.'' Finally, the model predicts that there is bistability between stationary and oscillatory glycolysis for a range of parameter values. We provide experimental support for this model prediction. Overall, the model can account for a diversity of islet behaviors described in the literature over the past 20 years.