Brenes Oscar, Pusch Michael, Morales Fernando
Departamento de Fisiología, Escuela de Medicina, Universidad de Costa Rica, San José 11501-2060, Costa Rica.
Centro de Investigación en Neurociencias (CIN), Universidad de Costa Rica, San José 11501-2060, Costa Rica.
Biomedicines. 2023 Sep 24;11(10):2622. doi: 10.3390/biomedicines11102622.
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 () 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 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.
先天性肌强直是一种遗传性肌肉疾病，主要特征为肌肉兴奋性过高，导致持续的放电爆发，这与非自主性后收缩的幅度和持续时间、肌肉僵硬及肥大相关。编码骨骼肌氯通道（ClC-1）的氯离子电压门控通道1（）基因的突变是导致该疾病的原因，该病通常被称为强直性氯通道病。已通过体外方法对突变通道的生物物理特性进行了探索和分析，为野生型和突变通道的一般功能/功能障碍提供了重要线索。在对突变进行详尽搜索后，我们在本综述中报告了文献中鉴定出的350多种不同突变。我们首先讨论ClC-1通道在骨骼肌功能中的生理作用。然后，利用所报道的自然发生突变的功能效应，我们描述ClC-1通道的生物物理和结构特征，以更新对每个ClC-1螺旋功能的认识，最后，我们试图指出关于该蛋白不同螺旋和环中突变效应的一些模式。
