Computational Neuroscience Laboratory, Department of Biomedical Engineering, Faculty of Electrical Engineering, Sahand University of Technology, Tabriz, Iran.
Computational Neuroscience Laboratory, Department of Biomedical Engineering, Faculty of Electrical Engineering, Sahand University of Technology, Tabriz, Iran.
Comput Methods Programs Biomed. 2014 Feb;113(2):697-704. doi: 10.1016/j.cmpb.2013.11.008. Epub 2013 Nov 24.
Purkinje neurons are the sole output neuron of the cerebellar cortex, and they generate high-frequency action potentials. Electrophysiological dysfunction of Purkinje neurons causes cerebellar ataxia. Mutant med mice have the lack of expression of the Scn8a gene. This gene encodes the NaV1.6 protein. In med Purkinje neurons, regular high-frequency firing is slowed, and med mice are ataxic. The aim of this study was to propose the neuroprotective drugs which could be useful for ataxia treatment in med mice, and to investigate the neuroprotective effects of these drugs by simulation. Simulation results showed that Kv4 channel inhibitors and BK channel activators restored the normal electrophysiological properties of the med Purkinje neurons. 4-Aminopyridine (4-AP) and acetazolamide (ACTZ) were proposed as neuroprotective drugs for Kv4 channel inhibitor and BK channel activator, respectively.
浦肯野神经元是小脑皮层的唯一输出神经元，它们产生高频动作电位。浦肯野神经元的电生理功能障碍导致小脑共济失调。Scn8a 基因突变型 med 小鼠缺乏 Scn8a 基因的表达。该基因编码 NaV1.6 蛋白。在 med 浦肯野神经元中，规则的高频放电减慢，med 小鼠出现共济失调。本研究旨在提出对 med 小鼠具有神经保护作用的药物，并用模拟来研究这些药物的神经保护作用。模拟结果表明，Kv4 通道抑制剂和 BK 通道激活剂恢复了 med 浦肯野神经元的正常电生理特性。4-氨基吡啶（4-AP）和乙酰唑胺（ACTZ）分别被提议作为 Kv4 通道抑制剂和 BK 通道激活剂的神经保护药物。
