PDF(Pubmed)
Abstract：
Myotonia congenita is a hereditary muscle disease mainly characterized by muscle hyperexcitability, which leads to a sustained burst of discharges that correlates with the magnitude and duration of involuntary aftercontractions, muscle stiffness, and hypertrophy. Mutations in the chloride voltage-gated channel 1 (CLCN1) gene that encodes the skeletal muscle chloride channel (ClC-1) are responsible for this disease, which is commonly known as myotonic chloride channelopathy. The biophysical properties of the mutated channel have been explored and analyzed through in vitro approaches, providing important clues to the general function/dysfunction of the wild-type and mutated channels. After an exhaustive search for CLCN1 mutations, we report in this review more than 350 different mutations identified in the literature. We start discussing the physiological role of the ClC-1 channel in skeletal muscle functioning. Then, using the reported functional effects of the naturally occurring mutations, we describe the biophysical and structural characteristics of the ClC-1 channel to update the knowledge of the function of each of the ClC-1 helices, and finally, we attempt to point out some patterns regarding the effects of mutations in the different helices and loops of the protein.
摘要：
先天性肌强直是一种遗传性肌肉疾病，主要表现为肌肉兴奋过度，这导致持续的放电爆发，与不自主的后收缩的程度和持续时间相关，肌肉僵硬，和肥大。编码骨骼肌氯化物通道（ClC-1）的氯化物电压门控通道1（CLCN1）基因突变是这种疾病的原因，通常被称为肌强直性氯化物通道病。已通过体外方法探索和分析了突变通道的生物物理特性，为野生型和突变通道的一般功能/功能障碍提供重要线索。在详尽搜索CLCN1突变后，我们在这篇综述中报告了文献中鉴定出的350余种不同的突变.我们开始讨论ClC-1通道在骨骼肌功能中的生理作用。然后，利用报道的天然突变的功能效应，我们描述了ClC-1通道的生物物理和结构特征，以更新每个ClC-1螺旋的功能知识，最后，我们试图指出一些关于蛋白质不同螺旋和环突变影响的模式。
