Kallen R G, Sheng Z H, Yang J, Chen L Q, Rogart R B, Barchi R L
David Mahoney Institute of Neurological Sciences, University of Pennsylvania School of Medicine, Philadelphia 19104.
Neuron. 1990 Feb;4(2):233-42. doi: 10.1016/0896-6273(90)90098-z.
The alpha subunit of a voltage-sensitive sodium channel characteristic of denervated rat skeletal muscle was cloned and characterized. The cDNA encodes a 2018 amino acid protein (SkM2) that is homologous to other recently cloned sodium channels, including a tetrodotoxin (TTX)-sensitive sodium channel from rat skeletal muscle (SkM1). The SkM2 protein is no more homologous to SkM1 than to the rat brain sodium channels and differs notably from SkM1 in having a longer cytoplasmic loop joining domains 1 and 2. Steady-state mRNA levels for SkM1 and SkM2 are regulated differently during development and following denervation: the SkM2 mRNA level is highest in early development, when TTX-insensitive channels predominate, but declines rapidly with age as SkM1 mRNA increases; SkM2 mRNA is not detectable in normally innervated adult skeletal muscle but increases greater than 100-fold after denervation; rat cardiac muscle has abundant SkM2 mRNA but no detectable SkM1 message. These findings suggest that SkM2 is a TTX-insensitive sodium channel expressed in both skeletal and cardiac muscle.
对去神经支配的大鼠骨骼肌特有的电压敏感性钠通道的α亚基进行了克隆和特性分析。该cDNA编码一种2018个氨基酸的蛋白质（SkM2），它与其他最近克隆的钠通道同源，包括来自大鼠骨骼肌的一种对河豚毒素（TTX）敏感的钠通道（SkM1）。SkM2蛋白与SkM1的同源性并不高于与大鼠脑钠通道的同源性，并且在连接结构域1和2的胞质环更长这一点上与SkM1有显著差异。SkM1和SkM2的稳态mRNA水平在发育过程中和去神经支配后受到不同的调节：SkM2 mRNA水平在发育早期最高，此时对TTX不敏感的通道占主导，但随着年龄增长SkM1 mRNA增加时迅速下降；在正常支配的成年骨骼肌中检测不到SkM2 mRNA，但去神经支配后增加超过100倍；大鼠心肌有丰富的SkM2 mRNA，但检测不到SkM1信息。这些发现表明SkM2是一种在骨骼肌和心肌中表达的对TTX不敏感的钠通道。
