A constitutively open potassium channel formed by KCNQ1 and KCNE3

Mutations in all four known KCNQ potassium channel or-subunit genes lead to human diseases(1-6). KCNQ1 (KvLQT1)(1) interacts with the beta-subunit KCN E1 (IsK, minK)(7) to form the slow, depolarization-activated potassium curr ent I-Ks(8,9) that is affected in some forms of cardiac arrhythmia. Here we show that the novel beta-subunit KCNE3 markedly changes KCNQ1 properties t o yield currents that are nearly instantaneous and depend linearly on volta ge, It also suppresses the currents of KCNQ4 and HERG potassium channels. I n 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 ass emble to form the potassium channel that is important for cyclic AMP-stimul ated intestinal chloride secretion and that is involved in secretory diarrh oea and cystic fibrosis.