N-terminal arginines modulate plasma-membrane localization of Kv7.1/KCNE1 channel complexes

  • Background and Objective: The slow delayed rectifier current (IKs) is important for cardiac action potential termination. The underlying channel is composed of Kv7.1 α-subunits and KCNE1 β-subunits. While most evidence suggests a role of KCNE1 transmembrane domain and C-terminus for the interaction, the N-terminal KCNE1 polymorphism 38G is associated with reduced IKs and atrial fibrillation (a human arrhythmia). Structure-function relationship of the KCNE1 N-terminus for IKs modulation is poorly understood and was subject of this study. Methods: We studied N-terminal KCNE1 constructs disrupting structurally important positively charged amino-acids (arginines) at positions 32, 33, 36 as well as KCNE1 constructs that modify position 38 including an N-terminal truncation mutation. Experimental procedures included molecular cloning, patch-clamp recording, protein biochemistry, real-time-PCR and confocal microscopy. Results: All KCNE1 constructs physically interacted with Kv7.1. IKs resulting from co-expression of Kv7.1 with non-atrial fibrillation ‘38S’ was greater than with any other construct. Ionic currents resulting from co-transfection of a KCNE1 mutant with arginine substitutions (‘38G-3xA’) were comparable to currents evoked from cells transfected with an N-terminally truncated KCNE1-construct (‘Δ1-38’). Western-blots from plasma-membrane preparations and confocal images consistently showed a greater amount of Kv7.1 protein at the plasma-membrane in cells co-transfected with the non-atrial fibrillation KCNE1-38S than with any other construct. Conclusions: The results of our study indicate that N-terminal arginines in positions 32, 33, 36 of KCNE1 are important for reconstitution of IKs. Furthermore, our results hint towards a role of these N-terminal amino-acids in membrane representation of the delayed rectifier channel complex.

Download full text files

Export metadata

Additional Services

Share in Twitter Search Google Scholar
Metadaten
Author:Zenawit Girmatsion, Peter Biliczki, Ina Takac, Christin Schwerthelm, Stefan H. HohnloserORCiD, Joachim EhrlichGND
URN:urn:nbn:de:hebis:30:3-237315
DOI:https://doi.org/doi:10.1371/journal.pone.0026967
ISSN:1932-6203
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/22073228
Parent Title (English):PLoS One
Publisher:PLoS
Place of publication:Lawrence, Kan.
Document Type:Article
Language:English
Date of Publication (online):2011/11/04
Year of first Publication:2011
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2011/12/27
Volume:6
Issue:11: e26967
Page Number:9
First Page:1
Last Page:9
HeBIS-PPN:287487024
Institutes:Medizin / Medizin
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Sammlung Biologie / Sondersammelgebiets-Volltexte
Licence (German):License LogoCreative Commons - Namensnennung 3.0