A minK-HERG complex regulates the cardiac potassium current I-Kr

Article

关键词: RECTIFIER K+ CURRENT;    XENOPUS-OOCYTES;    CHANNEL;    EXPRESSION;    PROTEIN;    CELLS;    LOCALIZATION;    ARRHYTHMIA;    MUTATIONS;    MEMBRANE;   

DOI  :  10.1038/40882

来源: SCIE

【 摘 要 】

MinK is a widely expressed protein of relative molecular mass similar to 15K that forms potassium channels by aggregation with other membrane proteins(1-3) MinK: governs :ion channel activiation(4) regulation by second messengers(5,6), and the function and structure of the ion conduction pathway(7,8). Association of minK with a channel protein known as KvLQT1 produces a voltage-gated outward K+ current (I-sK) resembling the slow cardiac repolarization current (I-Ks)(9,10). HERG, a human homologue of the ether-a-go-go gene of the fruitfly Drosophila melanogaster, encodes a protein that produces the rapidly activating cardiac delayed rectifier (I-Kr)(11,12). These two potassium currents, I-Kc, and I-Kr, provide the principal repolarizing currents in cardiac myocytes for the termination of action potentials(13,14). Although heterologously expressed HERG channels are largely indistinguishable from native cardiac I-Kr, a role for minK in this current is suggested by the diminished I-Kr in an atrial tumour line subjected to minK antisense suppression(15). Here we show that HERG and minK form a stable complex, and that this heteromultimerization regulates I-Kr activity. MinK, through the formation of heteromeric channel complexes, is thus central to the control of the heart rate and rhythm.

【 授权许可】

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