Pedersen Morten Gram
Department of Mathematics, Technical University of Denmark, Matematiktorvet 303, DK-2800 Kgs. Lyngby, Denmark.
J Theor Biol. 2007 Sep 21;248(2):391-400. doi: 10.1016/j.jtbi.2007.05.034. Epub 2007 Jun 2.
Pancreatic beta-cells show bursting electrical activity with a wide range of burst periods ranging from a few seconds, often seen in isolated cells, over tens of seconds (medium bursting), usually observed in intact islets, to several minutes. The phantom burster model [Bertram, R., Previte, J., Sherman, A., Kinard, T.A., Satin, L.S., 2000. The phantom burster model for pancreatic beta-cells. Biophys. J. 79, 2880-2892] provided a framework, which covered this span, and gave an explanation of how to obtain medium bursting combining two processes operating on different time scales. However, single cells are subjected to stochastic fluctuations in plasma membrane currents, which are likely to disturb the bursting mechanism and transform medium bursters into spikers or very fast bursters. We present a polynomial, minimal, phantom burster model and show that noise modifies the plateau fraction and lowers the burst period dramatically in phantom bursters. It is therefore unlikely that slow bursting in single cells is driven by the slow phantom bursting mechanism, but could instead be driven by oscillations in glycolysis, which we show are stable to random ion channel fluctuations. Moreover, so-called compound bursting can be converted to apparent slow bursting by noise, which could explain why compound bursting and mixed Ca(2+) oscillations are seen mainly in intact islets.
胰腺β细胞表现出爆发式电活动,爆发周期范围广泛,从几秒(常在分离的细胞中出现)到几十秒(中等爆发式,通常在完整胰岛中观察到),再到几分钟。“幻影爆发器”模型[伯特伦,R.,普雷维特,J.,谢尔曼,A.,基纳德,T.A.,萨廷,L.S.,2000年。胰腺β细胞的幻影爆发器模型。《生物物理学杂志》79,2880 - 2892]提供了一个涵盖此范围的框架,并解释了如何通过结合在不同时间尺度上运行的两个过程来实现中等爆发式。然而,单细胞会受到质膜电流的随机波动影响,这可能会干扰爆发机制,将中等爆发式细胞转变为尖峰发放细胞或非常快速的爆发式细胞。我们提出了一个多项式、最小化的幻影爆发器模型,并表明噪声会改变平台期比例,并显著降低幻影爆发器的爆发周期。因此,单细胞中的缓慢爆发式不太可能由缓慢的幻影爆发机制驱动,而可能由糖酵解振荡驱动,我们证明糖酵解振荡对随机离子通道波动具有稳定性。此外,所谓的复合爆发式可通过噪声转变为明显的缓慢爆发式,这可以解释为什么复合爆发式和混合Ca(2+)振荡主要在完整胰岛中出现。