George A L, Iyer G S, Kleinfield R, Kallen R G, Barchi R L
David Mahoney Institute of Neurological Sciences, Philadelphia, Pennsylvania.
Genomics. 1993 Mar;15(3):598-606. doi: 10.1006/geno.1993.1113.
Voltage-dependent sodium channels are essential for normal membrane excitability and contractility in adult skeletal muscle. The gene encoding the principal sodium channel alpha-subunit isoform in human skeletal muscle (SCN4A) has recently been shown to harbor point mutations in certain hereditary forms of periodic paralysis. We have carried out an analysis of the detailed structure of this gene including delineation of intron-exon boundaries by genomic DNA cloning and sequence analysis. The complete coding region of SCN4A is found in 32.5 kb of genomic DNA and consists of 24 exons (54 to > 2.2 kb) and 23 introns (97 bp-4.85 kb). The exon organization of the gene shows no relationship to the predicted functional domains of the channel protein and splice junctions interrupt many of the transmembrane segments. The genomic organization of sodium channels may have been partially conserved during evolution as evidenced by the observation that 10 of the 24 splice junctions in SCN4A are positioned in homologous locations in a putative sodium channel gene in Drosophila (para). The information presented here should be extremely useful both for further identifying sodium channel mutations and for gaining a better understanding of sodium channel evolution.
电压依赖性钠通道对于成年骨骼肌的正常膜兴奋性和收缩性至关重要。编码人类骨骼肌主要钠通道α亚基异构体的基因（SCN4A）最近已被证明在某些遗传性周期性麻痹形式中存在点突变。我们对该基因的详细结构进行了分析，包括通过基因组DNA克隆和序列分析来确定内含子-外显子边界。SCN4A的完整编码区存在于32.5 kb的基因组DNA中，由24个外显子（54至>2.2 kb）和23个内含子（97 bp - 4.85 kb）组成。该基因的外显子组织与通道蛋白的预测功能域无关，并且剪接位点中断了许多跨膜片段。钠通道的基因组组织在进化过程中可能部分保守，这一点可通过以下观察结果得到证明：SCN4A的24个剪接位点中有10个位于果蝇假定的钠通道基因（para）的同源位置。此处提供的信息对于进一步鉴定钠通道突变以及更好地理解钠通道进化都极为有用。
