Skip Navigation



Cardiovascular Research Advance Access [Accepted Manuscript] published online on February 15, 2008
Cardiovascular Research, doi:10.1093/cvr/cvn038
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
78/3/449    most recent
cvn038v2
cvn038v1
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Yang, Z.
Right arrow Articles by Murray, K. T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yang, Z.
Right arrow Articles by Murray, K. T.
Related Collections
Right arrowRelated Article
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org

Four and a Half LIM Protein 1: A Partner for KCNA5 in Human Atrium

Zhenjiang Yang*, Carrie F. Browning*, Haifa Hallaq, Liudmila Yermalitskaya, Jan Esker, Matthew R. Hall, Andrew J. Link{dagger}, Amy-Joan L. Ham#, Meagan J. McGrath**, Christina A. Mitchell** and Katherine T. Murray

Departments of Medicine, Pharmacology, Vanderbilt University School of Medicine, Nashville, TN
{dagger} Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN
# Biochemistry and Mass Spectrometry Research Center, Vanderbilt University School of Medicine, Nashville, TN
** Department of Biochemistry and Molecular Biology, Monash University, Victoria, Australia

Address for correspondence and reprints: Dr. Katherine T. Murray Division of Clinical Pharmacology Vanderbilt University School of Medicine Room 559 Preston Research Building 2220 Pierce Avenue Nashville, TN 37232-6602 Phone: (615) 936-3420 Fax: (615) 343-6334 Email: kathy.murray{at}vanderbilt.edu

Aims: Protein-protein interactions are critical for the normal membrane trafficking, localization, and function of voltage-gated ion channels. In human heart, the Shaker-related voltage-gated K+ channel KCNA5 {alpha}-subunit forms the major basis for an atrial-specific, ultra-rapid delayed rectifier K+ current, IKur. We sought to identify proteins that interact with KCNA5 in human atrium and to investigate their role in the IKur complex.

Methods and Results: Using a glutathione-S-transferase (GST)-KCNA5 C-terminal fusion protein and mass spectrometry-based methods, the scaffolding protein four and a half LIM (for Lin-11, Isl-1, and Mec3) protein 1 (FHL1) was identified as a potential protein partner for KCNA5. Immunoprecipitation experiments confirmed a physical interaction of FHL1 with the K+ channel complex in human atrium, as well as in Chinese hamster ovary (CHO) cells transfected with both KCNA5 and FHL1. In cotransfected cells, confocal microscopy demonstrated areas of colocalization after immunolabeling both proteins. To investigate the functional effects of this interaction, K+ currents were recorded in CHO cells transfected with KCNA5 in the absence and presence of FHL1 coexpression. With coexpression of FHL1, K+ current density was markedly increased, compared to cells expressing KCNA5 alone. This effect was associated with a shift in the voltage dependence of K+ channel activation to more positive potentials, consistent with findings for IKur in atrial myocytes. FHL1 also increased the extent and speed of K+ current slow inactivation, with additional effects on the voltage dependence and recovery of this process.

Conclusions: These results support a role for FHL1 as a key molecular component in the IKur complex in human atrium, where it likely regulates functional expression of KCNA5.

Time for primary review: 31 days

* These authors contributed equally to the manuscript.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?

Related Article

Four and a half LIM protein 1: a novel chaperone for atrium-specific Kv1.5 channels with a potential role in atrial arrhythmogenesis
Dobromir Dobrev and Erich Wettwer
Cardiovasc Res 2008 78: 411-412. [Extract] [Full Text] [PDF]



This article has been cited by other articles:


Home page
 Cardiovasc ResHome page
D. Dobrev and E. Wettwer
Four and a half LIM protein 1: a novel chaperone for atrium-specific Kv1.5 channels with a potential role in atrial arrhythmogenesis
Cardiovasc Res, June 1, 2008; 78(3): 411 - 412.
[Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.