KChIP2 is a core transcriptional regulator of cardiac excitability

Research output: Contribution to journalArticle


External Institution(s)

  • Case Western Reserve University


Original languageEnglish (US)
StatusPublished - Mar 6 2017


Arrhythmogenesis from aberrant electrical remodeling is a primary cause of death among patients with heart disease. Amongst a multitude of remodeling events, reduced expression of the ion channel subunit KChIP2 is consistently observed in numerous cardiac pathologies. However, it remains unknown if KChIP2 loss is merely a symptom or involved in disease development. Using rat and human derived cardiomyocytes, we identify a previously unobserved transcriptional capacity for cardiac KChIP2 critical in maintaining electrical stability. Through interaction with genetic elements, KChIP2 transcriptionally repressed the miRNAs miR-34b and miR-34c, which subsequently targeted key depolarizing (INa) and repolarizing (Ito) currents altered in cardiac disease. Genetically maintaining KChIP2 expression or inhibiting miR-34 under pathologic conditions restored channel function and moreover, prevented the incidence of reentrant arrhythmias. This identifies the KChIP2/miR-34 axis as a central regulator in developing electrical dysfunction and reveals miR-34 as a therapeutic target for treating arrhythmogenesis in heart disease.

    Research areas

  • INa, Ito, KChIP2, Kv4.3, Nav1.5, cell biology, heart failure (HF), human, human biology, medicine, rat

Citation formats



Nassal, DM, Wan, X, Liu, H, Maleski, D, Ramirez-Navarro, A, Moravec, CS, Ficker, E, Laurita, KR & Deschênes, I 2017, 'KChIP2 is a core transcriptional regulator of cardiac excitability', eLife, vol. 6. https://doi.org/10.7554/eLife.17304