计算机模拟的大鼠视神经动作电位变化

目的 目前已有的神经模型大多基于Hodgkin-Huxley理论,并且只考虑主要离子通道的影响.尽管主要离子通道如快速钠离子通道、快速钾离子通道和渗漏通道能够解释动作电位的产生和传递,但不足以解释动作电位的阈值差异和长期刺激的影响.而这些正是视觉假体需要考虑的问题.目前尚没有满意的视神经模型,因此本研究根据现有的各种视神经实验数据,对大鼠视神经(rat optic nerve,RON)进行建模.方法 在建模过程中考虑了小离子通道、轴突的空间特征、细胞外液的钾离子浓度变化.考虑到实验数据的易获性,使用大鼠神经作为模型;髓鞘的结构用双层电缆来明确模拟;提出一个新的"持续时间"A-current,并且与动力学特性被改进的其他常用离子通道一起用于模拟中;钾离子的累积和清除也采用一种新的方法来模拟.系统中大量的公式用Matlab编写的程序代码解决.结果 在系统中重现了以下的特点当存在4-氨基吡啶(4-aminopyridine,4-AP)药物时,动作电位持续时间增加;超极化后电位(hyperpolarizing afterpotential,AHP)随着去极化后电位(depolarizing afterpotential,DAP)出现;动作电位频率和四乙胺(tetraethylammonium,TEA)药物会影响超极化后电位的敏感性.在没有药物的时候模型仍重现了以下的特点一个单一的动作电位和一个短序列的动作电位后没有出现去极化后和超极化后电位;动作电位的振幅回复时间持续30 ms;去极化电流会显示早期超极化后电位的出现以及动作电位的适应性.结论 该模型成功地模拟了大鼠实验结果,包括会影响静息参数的长时间刺激实验,是视觉假体研究的重要课题.

Evoked membrane potential change in rat optic nerve fiber: Computer simulation

Objective The optic nerve is a key component regarding research on visual prosthesis. Previous pharmacological and electrical studies has pinned down the main features of the mechanisms underlying the nerve impulse in the rat optic nerve, and this work proposed a mathematical model to simulate these phenomena. Methods The main active nodal channels fast Na , persistent Na , slow K and a fast repolarizing K (A-current) were added on a double layer representation of the axon. A simplified representation of K accumulation and clearance in the vicinity of the Ranvier node wasintegrated in this model. Results The model was able to generate the following features. In the presence of 4-aminopyridine(4-AP), spike duration increased and a depolarizing afterpotential (DAP) appeared. In the presence of 4-AP and tetraethylammonium (TEA), the DAP was followed by a hyperpolarizing afterpotential (AHP) and the amplitude of this AHP increased with the frequency of the stimulation. In normal conditions (no drugs) DAP and AHP were absent after a single action potential (AP) and a short train of AP; there was a relative refractoriness in amplitude lasting for 30 ms after an AP; an early AHP was revealed by a continuous depolarizing current; and there was a partial spike adaptation for a long current step stimulus. Conclusion The model successfully reproduced previous experiments results including long-lasting stimulation experiment, which is known to modify nerve physiological parameter values and is a key issue for visual prosthesis research.