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Cardiovascular Research Advance Access first published online on December 14, 2008
This version [Corrected Proof] published online on January 10, 2009
Cardiovascular Research, doi:10.1093/cvr/cvn348
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2009. For permissions please email: journals.permissions@oxfordjournals.org.

Regulation of the ankyrin-B-based targeting pathway following myocardial infarction

Thomas J. Hund1,*, Patrick J. Wright1, Wen Dun2, Jedidiah S. Snyder1, Penelope A. Boyden2 and Peter J. Mohler1,3

1 Department of Internal Medicine, Division of Cardiovascular Medicine, University of Iowa Carver College of Medicine, 285 Newton Road, CBRB 2283, Iowa City, IA 52242, USA
2 Department of Pharmacology, Center for Molecular Therapeutics, Columbia University, New York, NY 10032, USA
3 Department of Molecular Physiology and Biophysics, University of Iowa Carver College of Medicine, Iowa City, IA, USA

* Corresponding author. Tel: +1 319 335 9691; fax: +1 319 353 5552. E-mail address: thomas-hund{at}uiowa.edu

Aims: Ion channel reorganization is a critical step in the pro-arrhythmogenic remodelling process that occurs in heart disease. Ankyrin-B (AnkB) is required for targeting and stabilizing ion channels, exchangers, and pumps. Despite a wealth of knowledge implicating the importance of AnkB in human cardiovascular physiology, nothing is known regarding the role of AnkB in common forms of acquired human disease.

Methods and results: We present the first report of AnkB regulation following myocardial infarction (MI). AnkB protein levels were reduced in the infarct border zone 5 days following coronary artery occlusion in the canine. We also observed a dramatic increase in AnkB mRNA levels 5 days post-occlusion. Surprisingly, the expression of the upstream AnkB cytoskeletal component β2-spectrin was unchanged in post-infarct tissues. However, protein levels and/or membrane expression of downstream AnkB-associated ion channels and transporters Na+/K+ ATPase, Na+/Ca2+ exchanger, and IP3 receptor were altered 5 days post-occlusion. Interestingly, protein levels of the protein phosphatase 2A, an AnkB-associated signalling protein, were significantly affected 5 days post-occlusion. AnkB and PP2A protein levels recovered by 14 days post-occlusion, whereas Na+/K+ ATPase levels recovered by 2 months post-occlusion.

Conclusion: These findings reveal the first evidence of ankyrin remodelling following MI and suggest an unexpected divergence point for regulation between ankyrin and the underlying cytoskeletal network. These findings suggest a logical, but unexpected, molecular mechanism underlying ion channel and transporter remodelling following MI.

KEYWORDS Arrhythmia (mechanisms); Infarction; Remodelling; Signal transduction; Cytoskeleton

Time for primary review: 23 days


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