miR-448 regulates potassium voltage-gated channel subfamily A member 4 (KCNA4) in ischemia and heart failure

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4 Scopus citations

Abstract

Background: MicroRNA miR-448 mediates some of the effects of ischemia on arrhythmic risk. Potassium voltage-gated channel subfamily A member 4 (KCNA4) encodes a Kv1.4 current that opens in response to membrane depolarization and is essential for regulating the action potential duration in heart. KCNA4 has a miR-448 binding site. Objective: We investigated whether miR-448 was involved in the regulation of KCNA4 messenger RNA expression in ischemia. Methods: Quantitative real-time reverse-transcriptase polymerase chain reaction was used to investigate the expression of KCNA4 and miR-448. Pull-down assays were used to examine the interaction between miR-448 and KCNA4. miR-448 decoy and binding site mutation were used to examine the specificity of the effect for KCNA4. Results: The expression of KCNA4 is diminished in ischemia and human heart failure tissues with ventricular tachycardia. Previously, we have shown that miR-448 is upregulated in ischemia and inhibition can prevent arrhythmic risk after myocardial infarction. The 3ʹ-untranslated region of KCNA4 has a conserved miR-448 binding site. miR-448 bound to this site directly and reduced KCNA4 expression and the transient outward potassium current. Inhibition of miR-448 restored KCNA4. Conclusion: These findings showed a link between Kv1.4 downregulation and miR-448–mediated upregulation in ischemia, suggesting a new mechanism for the antiarrhythmic effect of miR-448 inhibition.

Original languageEnglish (US)
Pages (from-to)730-736
Number of pages7
JournalHeart Rhythm
Volume20
Issue number5
DOIs
StatePublished - May 2023

Bibliographical note

Publisher Copyright:
© 2023 Heart Rhythm Society

Keywords

  • Arrhythmias
  • Cardiology
  • Hypoxia
  • Potassium channels
  • miR

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural

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