Potassium channel blockers as an effective treatment to restore impulse conduction in injured axons
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Most axons in the vertebral central nervous system are myelinated by oligodendrocytes. Myelin protects and insulates neuronal processes, enabling the fast, saltatory conduction unique to myelinated axons. Myelin disruption resulting from trauma and biochemical reaction is a common pathological event in spinal cord injury and chronic neurodegenerative diseases. Myelin damage-induced axonal conduction block is considered to be a significant contributor to the devastating neurological deficits resulting from trauma and illness. Potassium channels are believed to play an important role in axonal conduction failure in spinal cord injury and multiple sclerosis. Myelin damage has been shown to unmask potassium channels, creating aberrant potassium currents that inhibit conduction. Potassium channel blockade reduces this ionic leakage and improves conduction. The present review was mainly focused on the development of this technique of restoring axonal conduction and neurological function of demyelinated axons. The drug 4-aminopyridine has recently shown clinical success in treating multiple sclerosis symptoms. Further translational research has also identified several novel potassium channel blockers that may prove effective in restoring axonal conduction.
Keywordsaxon conduction potassium channel injury demyelination 4-aminopyridine
在脊椎中枢神经系统中, 少突胶质细胞能形成轴突的髓鞘。 髓鞘对轴突具有保护作用, 使轴突具有电绝缘的特性, 其独特的节段状结构使髓鞘化的神经轴突能快速、 跳跃式地传导神经冲动。 髓鞘损伤常见于脊髓损伤和一些慢性神经退行性疾病, 由其引起的轴突传导阻滞被认为是引起损伤相关的神经并发症的主要原因。 钾离子通道在发生于脊髓损伤和多发性硬化征的轴突传导阻滞中扮演重要角色。 髓鞘损伤后会暴露钾离子通道, 引起钾离子泄漏, 从而阻断神经传导。 将钾离子通道阻滞后, 离子泄漏得到抑制, 进而能促进神经传导。 本综述主要详细介绍了修复轴突神经传导功能技术的研究进展和脱髓鞘轴突的神经功能。 最近的研究表明, 4-氨基吡啶能有效治疗多发性硬化征。 此外, 转化型研究也筛选出了一些能有效修复轴突神经传导的新型的钾离子通道阻滞剂。
关键词轴突 传导 钾离子通道 损伤 脱髓鞘 4-氨基吡啶
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