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Cited by 171Cardiac electrophysiology and arrhythmiasIon channel regulation and functionCardiac Arrhythmias and Treatments

Transmural expression of transient outward potassium current subunits in normal and failing canine and human hearts

Zicha, Stephen, Xiao, Ling, Stafford, Sara, Cha, Tae Joon, Han, Wei, Varro, Andras, Nattel, Stanley·2004·The Journal of Physiology
DOI 10.1113/jphysiol.2004.075861
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Abstract

The transient outward current (Ito), an important contributor to transmural electrophysiological heterogeneity, is significantly remodelled in congestive heart failure (CHF). The molecular bases of transmural Ito gradients and CHF‐dependent ionic remodelling are incompletely understood. To elucidate these issues, we studied mRNA and protein expression of Kv4.3 and KChIP2, the principal alpha and beta subunits believed to form Ito, in epicardial and endocardial tissues and in isolated cardiomyocytes from control dogs and dogs with CHF induced by 240 beats min−1 ventricular tachypacing. CHF decreased Ito density in both epicardium and endocardium (by 73 and 55% at +60 mV, respectively), without a significant change in relative current density (endocardium/epicardium 0.11 control, 0.17 CHF). There were transmural gradients in mRNA expression of both Kv4.3 (endocardium/epicardium ratio 0.3 under control conditions) and KChIP2 (endocardium/epicardium ratio 0.2 control), which remained in the presence of CHF (Kv4.3 endocardium/epicardium ratio 0.4; KChIP2 0.4). There were qualitatively similar protein expression gradients in human and canine cardiac tissues and isolated canine cardiomyocytes; however, the KChIP2 gradient was only detectable with a highly selective monoclonal antibody and closely approximated the Ito density gradient. Kv4.3 mRNA expression was reduced by CHF, but KChIP2 mRNA was not significantly changed. CHF decreased Kv4.3 protein expression in canine cardiac tissues and cardiomyocytes, as well as in terminally failing human heart tissue samples, but KChIP2 protein was not down‐regulated in any of the corresponding sample sets. We conclude that both Kv4.3 and KChIP2 may contribute to epicardial–endocardial gradients in Ito, and that Ito down‐regulation in human and canine CHF appears due primarily to changes in Kv4.3.

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  • Expression patterns of various ion channels, both apico-basally and transmurally, are very similar between canine and human with some exceptions.

    “expression patterns of various ion channels both apico-basally (Szentadrassy, et al., 2005) and transmurally (Szabo, et al., 2005; Zicha, et al., 2004) with some exceptions, are very similar between these two species.”

    From Small and large animal models in cardiac contraction research: advantages and disadvantages (2014) · cites this paper as Zicha, et al., 2004

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Authors
Zicha, S., Xiao, L., Stafford, S., Cha, T. J., Han, W., Varro, A., & Nattel, S.
Affiliations
Montreal Heart Institute (CA)
Corresponding author
Nattel, Stanley
ORCID
Venue
The Journal of Physiology
Publisher
Wiley
Published
2004-12
Volume
561
Issue
3
Pages
735-748
ISSN
  • 0022-3751 (ISSN-L)
  • 1469-7793
DOI
10.1113/jphysiol.2004.075861
OpenAlex
W2151770583
Cited by
171
References
38
Citations by year
2026: 5 · 2025: 3 · 2024: 7 · 2023: 4 · 2022: 4 · 2021: 4 · 2020: 3 · 2019: 6 · 2018: 3 · 2017: 10 · 2016: 5 · 2015: 12 · 2014: 9 · 2013: 8 · 2012: 7
FWCI
6.75
Type
journal article
Language
en
Open access
closed
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 9 d)
Locations
  • The Journal of Physiology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Heart and Stroke Foundation of Canada
  • Mitacs
  • University of California, Davis
  • Canadian Institutes of Health Research
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Arrhythmias and Treatments
Keywords
transient outward potassium current, Kv4.3, KChIP2, congestive heart failure, transmural heterogeneity, cardiomyocytes, mRNA expression, protein expression, canine heart
MeSH terms
Animals, Calcium-Binding Proteins, Dogs, Heart Failure, Heart Ventricles, Humans, Myocardium, RNA, Messenger, Blotting, Western, Down-Regulation, Gene Expression, Potassium Channels, Voltage-Gated, Kv Channel-Interacting Proteins, Shal Potassium Channels

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