PRIMARY STRUCTURE AND FUNCTIONAL EXPRESSION OF THE BETA-1-SUBUNIT OF THE RAT-BRAIN SODIUM-CHANNEL
PRIMARY STRUCTURE AND FUNCTIONAL EXPRESSION OF THE BETA-1-SUBUNIT OF THE RAT-BRAIN SODIUM-CHANNEL
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DOI：
10.1126/science.1375395
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发表时间：
1992-05-08
期刊：
影响因子：
56.9
通讯作者：
CATTERALL, WA
中科院分区：
文献类型：
--
作者：
ISOM, LL;DEJONGH, KS;CATTERALL, WA
电压敏感性钠通道负责动作电位的起始和传播，因此对神经元兴奋性很重要。通过聚合酶链反应和文库筛选技术的组合分离编码大鼠脑钠通道β-1亚基的互补DNA克隆。推导的一级结构表明，β-1亚基是一个22，851-道尔顿蛋白，含有一个推定的跨膜结构域和四个潜在的细胞外N-连接糖基化位点，与生化数据一致。北方印迹分析揭示了大鼠脑、心脏、骨骼肌和脊髓中的1400个核苷酸的信使RNA。β-1亚基与α亚基的共表达增加了峰值钠电流的大小，加速了其失活，并将失活的电压依赖性转移到更负的膜电位。这些结果表明，β-1亚基是至关重要的组装，表达和功能调节的异源三聚体复合物的大鼠脑钠通道。
Voltage-sensitive sodium channels are responsible for the initiation and propagation of the action potential and therefore are important for neuronal excitability. Complementary DNA clones encoding the beta-1 subunit of the rat brain sodium channel were isolated by a combination of polymerase chain reaction and library screening techniques. The deduced primary structure indicates that the beta-1 subunit is a 22,851 -dalton protein that contains a single putative transmembrane domain and four potential extracellular N-linked glycosylation sites, consistent with biochemical data. Northern blot analysis reveals a 1400-nucleotide messenger RNA in rat brain, heart, skeletal muscle, and spinal cord. Coexpression of beta-1 subunits with alpha-subunits increases the size of the peak sodium current, accelerates its inactivation, and shifts the voltage dependence of inactivation to more negative membrane potentials. These results indicate that the beta-1 subunit is crucial in the assembly, expression, and functional modulation of the heterotrimeric complex of the rat brain sodium channel.