Sydney Medical School, University of Sydney, Sydney, Australia; Department of Neurology, St Vincent's Hospital, Sydney, Australia.
Brain and Mind Centre, University of Sydney, Sydney, Australia.
Neuropharmacology. 2018 Apr;132:98-107. doi: 10.1016/j.neuropharm.2017.04.045. Epub 2017 May 3.
With the rapid evolution of understanding of neurological channelopathies comes a need for sensitive tools to evaluate patients in clinical practice. Neurological channelopathies with a single-gene basis can manifest as seizures, headache, ataxia, vertigo, confusion, weakness and neuropathic pain and it is likely that other genetic factors contribute to the phenotype of many of these disorders. Ion channel dysfunction can result in abnormal cell membrane excitability but utilisation of advanced neurophysiology techniques has lagged behind developments in clinical, genetic and imaging evaluation of channelopathies. However, momentum in the application of in vivo axonal excitability testing sees these tests emerging as valuable tools, with the capacity to provide sensitive and specific insights into the mechanism of disease. While single-channel function cannot be directly measured in vivo, evaluation of subjects with single-gene channelopathies has provided insights into the effects of mutation-related alterations of membrane excitability, as well as compensatory adaptive changes. By showing how ion channel dysfunction can affect axonal excitability in vivo, studies of the excitability of peripheral nerve axons complement in vitro analysis of single channel activity. The interpretation of results is enhanced by mathematical modelling of axonal function and insights provided by in vitro work. This article is part of the Special Issue entitled 'Channelopathies.'
随着对神经通道病理解的迅速发展，需要有敏感的工具来评估临床实践中的患者。具有单基因基础的神经通道病可表现为癫痫发作、头痛、共济失调、眩晕、意识模糊、无力和神经性疼痛，而且许多这些疾病的表型可能还有其他遗传因素。离子通道功能障碍可导致细胞膜兴奋性异常，但高级神经生理学技术的应用落后于通道病的临床、遗传和影像学评估的发展。然而，应用活体轴突兴奋性测试的势头使这些测试成为有价值的工具，有能力提供对疾病机制的敏感和特异性见解。虽然不能直接在体内测量单通道功能，但对具有单基因通道病的受试者的评估提供了对与膜兴奋性相关的突变改变以及代偿性适应性变化的见解。通过展示离子通道功能障碍如何影响体内轴突的兴奋性，对周围神经轴突兴奋性的研究补充了对单通道活性的体外分析。通过对轴突功能的数学建模和体外工作提供的见解，增强了对结果的解释。本文是特刊“通道病”的一部分。
