不同刺激方案下突触前游离钙动力学的定量模型
A quantitative model for presynaptic free calcium dynamics during different stimulation protocols
摘要：
在一个数学模型中研究了神经元突触前游离钙动力学。该模型包括通过电压依赖性钙通道的钙内流、通过内源性和外源性缓冲剂的钙缓冲以及通过ATP驱动的质膜钙泵和钠/钙交换器的钙外流。我们希望支持一种特定的建模方式，这种方式从单个蛋白质的水平开始。每种蛋白质都由单个蛋白质实验确定的特征表示，并且被认为与神经元类型广泛无关。这使得该模型的应用程序，以不同类别的神经元和实验。该程序被证明为单扣的锥体神经元的大鼠新皮层。Koester和Sakmann（2000，J. Physiol.，529，625）是定量再现。该模型使我们能够重建神经元中的游离钙动力学，因为它本来没有荧光指示剂，从荧光数据开始。我们讨论了不同的钙反应，发现在高频刺激过程中，游离钙的积累发生在一定的阈值刺激频率以上。阈值频率取决于实验中使用的荧光指示剂的量。
英文摘要：
The presynaptic free calcium dynamics of neurons due to various stimulation protocols is investigated in a mathematical model. The model includes calcium influx through voltage-dependent calcium channels, calcium buffering by endogenous and exogenous buffers as well as calcium efflux through ATP-driven plasma membrane calcium pumps and sodium/calcium exchangers. We want to support a specific way of modeling which starts on the level of single proteins. Each protein is represented by characteristics that are determined by single protein experiments and that are considered to be widely independent of neuron types. This allows the applications of the model to different classes of neurons and experiments. The procedure is demonstrated for single boutons of pyramidal neurons of the rat neocortex. The corresponding fluorescence measurements of Koester & Sakmann (2000, J. Physiol., 529, 625) are quantitatively reproduced. The model enables us to reconstruct the free calcium dynamics in neurons as it would have been without fluorescence indicators starting from the fluorescence data. We discuss the different calcium responses and find that during high-frequency stimulation an accumulation of free calcium occurs above some threshold stimulation frequency. The threshold frequency depends on the amount of fluorescence indicator used in the experiment.
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