PRIMARY STRUCTURE AND FUNCTIONAL EXPRESSION OF THE HUMAN CARDIAC TETRODOTOXIN-INSENSITIVE VOLTAGE-DEPENDENT SODIUM-CHANNEL
PRIMARY STRUCTURE AND FUNCTIONAL EXPRESSION OF THE HUMAN CARDIAC TETRODOTOXIN-INSENSITIVE VOLTAGE-DEPENDENT SODIUM-CHANNEL
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DOI：
10.1073/pnas.89.2.554
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发表时间：
1992-01-15
影响因子：
11.1
通讯作者：
KALLEN, RG
中科院分区：
文献类型：
--
作者：
GELLENS, ME;GEORGE, AL;KALLEN, RG
人心脏主要的电压敏感性钠通道已被克隆、测序和功能表达。命名为hH 1的cDNA编码一个2016个氨基酸的蛋白质，该蛋白质与钠通道多基因家族的其他成员同源，并且与大鼠心脏和未成熟和去神经大鼠骨骼肌的河豚毒素不敏感钠通道特征具有> 90%的同一性。北方印迹分析表明，一个几乎等于9.0-β-淀粉酶的转录本在人心房和心室心肌中表达，但在成人骨骼肌、脑、子宫肌层、肝或脾中不表达。当在非洲爪蟾卵母细胞中表达时，hH 1表现出类似于天然心脏钠通道的快速激活和失活动力学。hH 1对钠离子的单通道电导约为同源大鼠通道的两倍，并且hH 1对河豚毒素的阻断更具抗性（IC 50 = 5.7 μ M）。hH 1对μ-芋螺毒素也有抗性，但对治疗浓度的利多卡因以使用依赖性方式阻断敏感。
The principal voltage-sensitive sodium channel from human heart has been cloned, sequenced, and functionally expressed. The cDNA, designated hH1, encodes a 2016-amino acid protein that is homologous to other members of the sodium channel multigene family and bears > 90% identity to the tetrodotoxin-insensitive sodium channel characteristic of rat heart and of immature and denervated rat skeletal muscle. Northern blot analysis demonstrates an almost-equal-to 9.0-kilobase transcript expressed in human atrial and ventricular cardiac muscle but not in adult skeletal muscle, brain, myometrium, liver, or spleen. When expressed in Xenopus oocytes, hH1 exhibits rapid activation and inactivation kinetics similar to native cardiac sodium channels. The single channel conductance of hH1 to sodium ions is about twice that of the homologous rat channel and hH1 is more resistant to block by tetrodotoxin (IC50 = 5.7-mu-M). hH1 is also resistant to mu-conotoxin but sensitive to block by therapeutic concentrations of lidocaine in a use-dependent manner.