KCNE4 is an inhibitory subunit to the KCNQ1 channel

Abstract

KCNE4 is a membrane protein belonging to a family of single transmembrane domain proteins known to have dramatic effect on the gating of certain potassium channels. However, no functional role of KCNE4 has been suggested so far. In the present paper we demonstrate that KCNE4 is an inhibitory subunit to KCNQ1 channels. Co-expression of KCNQ1 and KCNE4 in Xenopus oocytes completely inhibited the KCNQ1 current. This was reproduced in mammalian CHO-K1 cells. Experiments with delayed expression of mRNA coding for KCNE4 in KCNQ1-expressing oocytes suggested that KCNE4 exerts its effect on KCNQ1 channels already expressed in the plasma membrane. This notion was supported by immunocytochemical studies and Western blotting, showing no significant difference in plasma membrane expression of KCNQ1 channels in the presence or absence of KCNE4. The impact of KCNE4 on KCNQ1 was specific since no effect of KCNE4 could be detected if co-expressed with KCNQ2-5 channels or hERG1 channels. RT-PCR studies revealed high KCNE4 expression in embryos and adult uterus, where significant expression of KCNQ1 channels has also been demonstrated.

KCNE1 Subunits Require Co-assembly with K+ Channels for Efficient Trafficking and Cell Surface Expression

“…Although these results cannot rule out Q1-E1 complex assembly in the cis-Golgi, the sheer abundance of unpartnered E1 peptides in the ER and co-immunoprecipitation of the immature and unglycosylated E1 with Q1 strongly suggest that Q1-E1 complex assembly occurs in the ER. An ER-based assembly for Q1-E1 complexes directly contradicts two previous functional studies where it was proposed that complex assembly occurs at the plasma membrane (14,15). The basis for this proposal was that Xenopus oocytes expressing unpartnered Q1 K ϩ currents could be converted to KCNE-modulated currents within 24 h by a subsequent injection of KCNE mRNA.…”

“…Two different studies suggest that Q1-E1 complex formation occurs at the plasma membrane, which would require both proteins to traffic through the secretory pathway independently (14,15). More recently, it was proposed that Q1-E1 assembly occurs in the ER because mutant E1 proteins could retain Q1 channels there (16).…”

Anxiolytic Effects of Maxipost (BMS-204352) and Retigabine via Activation of Neuronal Kv7 Channels

“…Although functional channels are obtained by expression of K v 7 ␣-subunits alone, ␤-subunits belonging to the KCNE family are reported to influence the expression, pharmacology, and voltage-dependence of the ␣-subunits (Schroeder et al, 2000b;Wang et al, 2000;Grunnet et al, 2002). There are five known ␣-subunits (K v 7.1-K v 7.5), and the sequence alignment of the hydrophobic regions divides them into two groups, one comprising K v 7.1 and the other K v 7.2 to K v 7.5.…”

Protein distribution of Kcnq1, Kcnh2, and Kcne3 potassium channel subunits during mouse embryonic development

“…However, three novel Kcne (Kcne3, Kcne4, and Kcne5) family members have been recently reported, which are also widely distributed in the adult mouse (Grunnet et al, 2002(Grunnet et al, , 2003Teng et al, 2003). Coexpression experiments of Kcnq1 and Kcne3 subunits give rise to a constitutively opened pore (Mazhari et al, 2002), whereas coexpression with either Kcne4 or Kcne5 suppresses the current I Ks (Lundquist et al, 2005).…”