Ionic mechanisms and Ca2+ dynamics underlying the glucose response of pancreatic β cells: a simulation study.
Ionic mechanisms and Ca2+ dynamics underlying the glucose response of pancreatic β cells: a simulation study.
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DOI：
10.1085/jgp.201110611
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发表时间：
2011-07
期刊：
影响因子：
--
通讯作者：
Noma A
中科院分区：
文献类型：
--
作者：
Cha CY;Nakamura Y;Himeno Y;Wang J;Fujimoto S;Inagaki N;Earm YE;Noma A
为了阐明胰腺β细胞对不同葡萄糖浓度的反应的机制（[G]），将电生理学发现整合到数学细胞模型中。内质网Ca ~（2+）动力学也得到改善。通过证明静态电位、伴随Ca 2+瞬变的爆发-爆发间电事件以及分别在0-6、7-18和>19 mM的[G]范围内的动作电位的连续激发来验证该模型。这些对葡萄糖的反应是完全可逆的。动作电位，输入阻抗，和Ca 2+瞬变与实验测量结果吻合良好。通过铅电位分析，量化了单个电流成分的贡献，研究了爆发-爆发间节律的离子机制。该分析表明，在爆发间期期间缓慢的电位变化可归因于细胞内离子和/或代谢物对离子通道或转运蛋白的不同程度的修饰，取决于[G]。腺苷三磷酸敏感性K+电流在8 mM [G]下开启和关闭动作电位重复放电的主要作用在更高[G]下被Ca 2+或Na+依赖性电流所取代，这些电流由质膜Ca 2+泵、Na+/K+泵、Na+/Ca 2+交换器和TRPM通道产生。ER对Ca ~（2+）的积累和释放也对慢电节律产生了强烈的影响。我们的结论是，目前的数学模型是有用的量化的作用，在整个细胞反应的基础上的实验结果的个别功能组件。
To clarify the mechanisms underlying the pancreatic β-cell response to varying glucose concentrations ([G]), electrophysiological findings were integrated into a mathematical cell model. The Ca2+ dynamics of the endoplasmic reticulum (ER) were also improved. The model was validated by demonstrating quiescent potential, burst–interburst electrical events accompanied by Ca2+ transients, and continuous firing of action potentials over [G] ranges of 0–6, 7–18, and >19 mM, respectively. These responses to glucose were completely reversible. The action potential, input impedance, and Ca2+ transients were in good agreement with experimental measurements. The ionic mechanisms underlying the burst–interburst rhythm were investigated by lead potential analysis, which quantified the contributions of individual current components. This analysis demonstrated that slow potential changes during the interburst period were attributable to modifications of ion channels or transporters by intracellular ions and/or metabolites to different degrees depending on [G]. The predominant role of adenosine triphosphate–sensitive K+ current in switching on and off the repetitive firing of action potentials at 8 mM [G] was taken over at a higher [G] by Ca2+- or Na+-dependent currents, which were generated by the plasma membrane Ca2+ pump, Na+/K+ pump, Na+/Ca2+ exchanger, and TRPM channel. Accumulation and release of Ca2+ by the ER also had a strong influence on the slow electrical rhythm. We conclude that the present mathematical model is useful for quantifying the role of individual functional components in the whole cell responses based on experimental findings.
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