Coassembly of K(v)LQT1 and minK (IsK) proteins to form cardiac I-Ks potassium channel
Coassembly of K(v)LQT1 and minK (IsK) proteins to form cardiac I-Ks potassium channel
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DOI：
10.1038/384080a0
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发表时间：
1996-11-07
期刊：
影响因子：
64.8
通讯作者：
Keating, MT
中科院分区：
文献类型：
--
作者：
Sanguinetti, MC;Curran, ME;Keating, MT
缓慢激活的延迟整流钾电流（I-Ks）调节复极化或心脏动作电位。I-Ks通道的分子结构尚不清楚，但生理学数据表明I-Ks通道的一种组分是minK（参考文献1-6），这是一种具有单一假定跨膜结构域的130个氨基酸的蛋白质（7）。这种蛋白质的大小和结构使得minK不太可能单独形成功能通道（8，9）。我们以前使用定位克隆技术来确定一个新的假定的K+通道基因，KVLQT 1（10）。这种基因的突变会导致长QT综合征，这是一种遗传性疾病，会增加心律失常导致猝死的风险。在这里，我们表明，KVLQT 1编码的K+通道的生物物理特性不同于其他已知的心脏电流。我们认为K（v）LQT 1可能与另一个亚基共组装形成心肌细胞的功能通道。K（v）LQT 1与minK共表达诱导的电流与心脏I-Ks几乎相同。因此，K（v）LQT 1是与minK共组装形成I-Ks通道的亚基，I-Ks功能障碍是心律失常的原因。
THE slowly activating delayed-rectifier K+ current, I-Ks, modulates the repolarization or cardiac action potentials. The molecular structure of the I-Ks, channel is not known, but physiological data indicate that one component of the I-Ks channel is minK (refs 1-6), a 130-amino-acid protein with a single putative transmembrane domain(7). The size and structure of this protein is such that it is unlikely that minK alone forms functional channels(8,9). We have previously used positional cloning techniques to define a new putative K+-channel gene, KVLQT1(10). Mutations in this gene cause long-QT syndrome, an inherited disorder that increases the risk of sudden death from cardiac arrhythmias. Here se show that KVLQT1 encodes a K+ channel with biophysical properties unlike other known cardiac currents. We considered that K(v)LQT1 might coassemble with another subunit to form functional channels in cardiac myocytes. Coexpression of K(v)LQT1 with minK induced a current that was almost identical to cardiac I-Ks. Therefore, K(v)LQT1 is the subunit that coassembles with minK to form I-Ks channels and I-Ks dysfunction is a cause of cardiac arrhythmia.