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KCNE4 can co‐associate with the I Ks (KCNQ1–KCNE1) channel complex
Author(s) -
Manderfield Lauren J.,
George Alfred L.
Publication year - 2008
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2008.06294.x
Subject(s) - potassium channel , protein subunit , microbiology and biotechnology , heterologous expression , biology , immunoprecipitation , chemistry , neuroscience , biochemistry , biophysics , gene , recombinant dna
Voltage‐gated potassium (K V ) channels can form heteromultimeric complexes with a variety of accessory subunits, including KCNE proteins. Heterologous expression studies have demonstrated diverse functional effects of KCNE subunits on several K V channels, including KCNQ1 (K V 7.1) that, together with KCNE1, generates the slow‐delayed rectifier current ( I Ks ) important for cardiac repolarization. In particular, KCNE4 exerts a strong inhibitory effect on KCNQ1 and other K V channels, raising the possibility that this accessory subunit is an important potassium current modulator. A polyclonal KCNE4 antibody was developed to determine the human tissue expression pattern and to investigate the biochemical associations of this protein with KCNQ1. We found that KCNE4 is widely and variably expressed in several human tissues, with greatest abundance in brain, liver and testis. In heterologous expression experiments, immunoprecipitation followed by immunoblotting was used to establish that KCNE4 directly associates with KCNQ1, and can co‐associate together with KCNE1 in the same KCNQ1 complex to form a ‘triple subunit’ complex (KCNE1–KCNQ1–KCNE4). We also used cell surface biotinylation to demonstrate that KCNE4 does not impair plasma membrane expression of either KCNQ1 or the triple subunit complex, indicating that biophysical mechanisms probably underlie the inhibitory effects of KCNE4. The observation that multiple KCNE proteins can co‐associate with and modulate KCNQ1 channels to produce biochemically diverse channel complexes has important implications for understanding K V channel regulation in human physiology.