Department of Mechanical and Aerospace Engineering, North Carolina State University, Raleigh, NC 27695-7910.
J Biomech Eng. 2024 Nov 1;146(11). doi: 10.1115/1.4065743.
The precise mechanism behind the supply of adenosine triphosphate (ATP) to approximately half of the presynaptic release sites in axons that lack a stationary mitochondrion is not fully understood. This paper presents a mathematical model designed to simulate the transient ATP concentration in presynaptic en passant boutons. The model is utilized to investigate how the ATP concentration responds to increased ATP demand during neuronal firing in boutons with a stationary mitochondrion and those without one. The analysis suggests that neuron firing may cause oscillations in the ATP concentrations, with peak-to-peak amplitudes ranging from 0.06% to 5% of their average values. However, this does not deplete boutons lacking a mitochondrion of ATP; for physiologically relevant values of model parameters, their concentration remains approximately 3.75 times higher than the minimum concentration required for synaptic activity. The variance in average ATP concentrations between boutons containing a stationary mitochondrion and those lacking one ranges from 0.3% to 0.8%, contingent on the distance between the boutons. The model indicates that diffusion-driven ATP transport is rapid enough to adequately supply ATP molecules to boutons lacking a stationary mitochondrion.
目前，人们尚未完全了解为缺乏定位于线粒体的轴突中约一半的突触前释放位点提供三磷酸腺苷（ATP）的精确机制。本文提出了一个数学模型，旨在模拟突触前游走型末梢内的瞬态 ATP 浓度。该模型用于研究在具有定位于线粒体的末梢和不具有定位于线粒体的末梢中，神经元放电时 ATP 需求增加时 ATP 浓度如何响应。分析表明，神经元放电可能会引起 ATP 浓度的振荡，其峰峰值幅度范围为其平均值的 0.06%至 5%。然而，这不会耗尽缺乏线粒体的末梢中的 ATP；对于模型参数的生理相关值，其浓度仍然大约比突触活动所需的最小浓度高 3.75 倍。含有定位于线粒体的末梢和缺乏定位于线粒体的末梢之间的平均 ATP 浓度的差异范围为 0.3%至 0.8%，这取决于末梢之间的距离。该模型表明，扩散驱动的 ATP 运输速度足够快，可以为缺乏定位于线粒体的末梢提供足够的 ATP 分子。
