KvLQT1, a voltage-gated potassium channel responsible for human cardiac arrhythmias
KvLQT1, a voltage-gated potassium channel responsible for human cardiac arrhythmias
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DOI：
10.1073/pnas.94.8.4017
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发表时间：
1997-04-15
影响因子：
11.1
通讯作者：
Blanar, MA
中科院分区：
文献类型：
--
作者：
Yang, WP;Levesque, PC;Blanar, MA
长QT综合征的临床特征是由突发性危及生命的心律失常引起的，特别是多形性室性心动过速尖端扭转型室性心动过速。 KVLQT1 已被确定为人类 11 号染色体连锁基因，与 50% 以上的遗传性长 QT 综合征有关。在这里，我们描述了全长 KVLQT1 cDNA 的克隆及其功能表达。 KVLQT1 编码 676 个氨基酸的多肽，其结构特征与电压门控钾通道相似。 KvLQT1 在非洲爪蟾卵母细胞和人胚胎肾细胞中的表达会引发快速激活的 K+ 选择性外向电流。 I-Kr 特异性阻滞剂 E-4031 和多非利特不会抑制 KvLQT1，而氯非铵（一种具有诱发尖端扭转型室性倾向的 III 类抗心律失常药）可显着抑制电流。卵母细胞中 cAMP 水平的升高几乎使 KvLQT1 电流的幅度增加一倍。 minK 与 KvLQT1 的共表达导致电导的药理学和生物物理特性比心脏中其他已知的延迟整流 K+ 电流更类似于 I-K。
The clinical features of long QT syndrome result from episodic life threatening cardiac arrhythmias, specifically the polymorphic ventricular tachycardia torsades de pointes. KVLQT1 has been established as the human chromosome 11-linked gene responsible for more than 50% of inherited long QT syndrome. Here we describe the cloning of a full-length KVLQT1 cDNA and its functional expression. KVLQT1 encodes a 676-amino acid polypeptide with structural characteristics similar to voltage-gated potassium channels. Expression of KvLQT1 in Xenopus oocytes and in human embryonic kidney cells elicits a rapidly activating, K+-selective outward current. The I-Kr-specific blockers, E-4031 and dofetilide, do not inhibit KvLQT1, whereas clofilium, a class III antiarrhythmic agent with the propensity to induce torsades de pointes, substantially inhibits the current. Elevation of cAMP levels in oocytes nearly doubles the amplitude of KvLQT1 currents. Coexpression of minK with KvLQT1 results in a conductance with pharmacological and biophysical properties more similar to I-Ks than other known delayed rectifier K+ currents in the heart.