Schroeder B C, Waldegger S, Fehr S, Bleich M, Warth R, Greger R, Jentsch T J
Zentrum für Molekulare Neurobiologie Hamburg, Hamburg University, Germany.
Nature. 2000 Jan 13;403(6766):196-9. doi: 10.1038/35003200.
Mutations in all four known KCNQ potassium channel alpha-subunit genes lead to human diseases. KCNQ1 (KvLQT1) interacts with the beta-subunit KCNE1 (IsK, minK) to form the slow, depolarization-activated potassium current I(Ks) that is affected in some forms of cardiac arrhythmia. Here we show that the novel beta-subunit KCNE3 markedly changes KCNQ1 properties to yield currents that are nearly instantaneous and depend linearly on voltage. It also suppresses the currents of KCNQ4 and HERG potassium channels. In the intestine, KCNQ1 and KCNE3 messenger RNAs colocalized in crypt cells. This localization and the pharmacology, voltage-dependence and stimulation by cyclic AMP of KCNQ1/KCNE3 currents indicate that these proteins may assemble to form the potassium channel that is important for cyclic AMP-stimulated intestinal chloride secretion and that is involved in secretory diarrhoea and cystic fibrosis.
所有四个已知的KCNQ钾通道α亚基基因突变都会导致人类疾病。KCNQ1（KvLQT1）与β亚基KCNE1（IsK，minK）相互作用，形成缓慢的、去极化激活的钾电流I(Ks)，某些形式的心律失常会影响该电流。在此我们表明，新型β亚基KCNE3显著改变KCNQ1的特性，产生几乎瞬间且呈电压线性依赖的电流。它还抑制KCNQ4和HERG钾通道的电流。在肠道中，KCNQ1和KCNE3信使核糖核酸共定位于隐窝细胞中。KCNQ1/KCNE3电流的这种定位以及药理学、电压依赖性和环磷酸腺苷刺激作用表明，这些蛋白质可能组装形成对环磷酸腺苷刺激的肠道氯化物分泌很重要且参与分泌性腹泻和囊性纤维化的钾通道。
