Cooper E C, Jan L Y
Department of Neurology, Biochemistry, and Howard Hughes Medical Institute, University of California, San Francisco, CA 94143, USA.
Proc Natl Acad Sci U S A. 1999 Apr 27;96(9):4759-66. doi: 10.1073/pnas.96.9.4759.
What do epilepsy, migraine headache, deafness, episodic ataxia, periodic paralysis, malignant hyperthermia, and generalized myotonia have in common? These human neurological disorders can be caused by mutations in genes for ion channels. Many of the channel diseases are "paroxysmal disorders" whose principal symptoms occur intermittently in individuals who otherwise may be healthy and active. Some of the ion channels that cause human neurological disease are old acquaintances previously cloned and extensively studied by channel specialists. In other cases, however, disease-gene hunts have led the way to the identification of new channel genes. Progress in the study of ion channels has made it possible to analyze the effects of human neurological disease-causing channel mutations at the level of the single channel, the subcellular domain, the neuronal network, and the behaving organism.
癫痫、偏头痛、耳聋、发作性共济失调、周期性麻痹、恶性高热和全身性肌强直有什么共同之处？这些人类神经系统疾病可能由离子通道基因的突变引起。许多通道疾病是“发作性疾病”，其主要症状在原本可能健康活跃的个体中间歇性出现。一些导致人类神经系统疾病的离子通道是通道专家之前克隆并广泛研究过的“老相识”。然而，在其他情况下，疾病基因搜寻引领了新通道基因的鉴定。离子通道研究的进展使得在单通道、亚细胞结构域、神经网络和活体生物层面分析导致人类神经系统疾病的通道突变的影响成为可能。
