title: KCNE2 confers background current characteristics to the cardiac KCNQ1 potassium channel.
abstract: Mutations in HERG and KCNQ1 (or KVLQT1) genes cause the life-threatening Long QT syndrome. These genes encode K(+) channel pore-forming subunits that associate with ancillary subunits from the KCNE family to underlie the two components, I(Kr) and I(Ks), of the human cardiac delayed rectifier current I(K). The KCNE family comprises at least three members. KCNE1 (IsK or MinK) recapitulates I(Ks) when associated with KCNQ1, whereas it augments the amplitude of an I(Kr)-like current when co-expressed with HERG. KCNE3 markedly changes KCNQ1 as well as HERG current properties. So far, KCNE2 (MirP1) has only been shown to modulate HERG current. Here we demonstrate the interaction of KCNE2 with the KCNQ1 subunit, which results in a drastic change of KCNQ1 current amplitude and gating properties. Furthermore, KCNE2 mutations also reveal their specific functional consequences on KCNQ1 currents. KCNQ1 and HERG appear to share unique interactions with KCNE1, 2 and 3 subunits. With the exception of KCNE3, mutations in all these partner subunits have been found to lead to an increased propensity for cardiac arrhythmias.
authors: Institut de Pharmacologie Moléculaire et Cellulaire, CNRS UPR 411, 660 route des Lucioles, Sophia Antipolis, 06560 Valbonne, France.
authors: N
authors: N
authors: Tinel
authors: S
authors: S
authors: Diochot
authors: M
authors: M
authors: Borsotto
authors: M
authors: M
authors: Lazdunski
authors: J
authors: J
authors: Barhanin
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000235:genetics; D019556:COS Cells; D027682:Cation Transport Proteins; D002460:Cell Line; D002839:Chromans / Q000494:pharmacology; D004268:DNA-Binding Proteins; D000072237:ERG1 Potassium Channel; D004594:Electrophysiology; D051638:Ether-A-Go-Go Potassium Channels; D006801:Humans; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; D008133:Long QT Syndrome / Q000235:genetics; D009154:Mutation; D009206:Myocardium / Q000378:metabolism*; D015221:Potassium Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D011485:Protein Binding; D013449:Sulfonamides / Q000494:pharmacology; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D014981:Xenopus
chemical_list: D027682:Cation Transport Proteins; D002839:Chromans; D004268:DNA-Binding Proteins; C072312:ERG protein, human; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C418492:KCNE3 protein, human; C000606913:KCNH2 protein, human; C092509:KCNH6 protein, human; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D013449:Sulfonamides; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; C059983:potassium channel protein I(sk); C103474:6-cyano-4-(N-ethylsulfonyl-N-methylamino)-3-hydroxy-2,2-dimethylchromane