Skip to content

Regulation of Kv4.3 and hERG potassium channels by KChIP2 isoforms and DPP6 and response to the dual K+ channel activator NS3623

Research output: Contribution to journalArticle (Academic Journal)

Original languageEnglish
Pages (from-to)120-130
Number of pages11
JournalBiochemical Pharmacology
Early online date31 Jan 2018
DateAccepted/In press - 22 Jan 2018
DateE-pub ahead of print - 31 Jan 2018
DatePublished (current) - 1 Apr 2018


Transient outward potassium current (Ito) contributes to early repolarization of many mammalian cardiac action potentials, including human, whilst the rapid delayed rectifier K+ current (IKr) contributes to later repolarization. Fast Ito channels can be produced from the Shal family KCNDE gene product Kv4.3s, although accessory subunits including KChIP2.x and DPP6 are also needed to produce a near physiological Ito. In this study, the effect of KChIP2.1 & KChIP2.2 (also known as KChIP2b and KChIP2c respectively), alone or in conjunction with the accessory subunit DPP6, on both Kv4.3 and hERG were evaluated. A dual Ito and IKr activator, NS3623, has been recently proposed to be beneficial in heart failure and the action of NS3623 on the two channels was also investigated. Whole-cell patch-clamp experiments were performed at 33 ± 1 °C on HEK293 cells expressing Kv4.3 or hERG in the absence or presence of these accessory subunits. Kv4.3 current magnitude was augmented by co-expression with either KChIP2.2 or KChIP2.1 and KChIP2/DPP6 with KChIP2.1 producing a greater effect than KChIP2.2. Adding DPP6 removed the difference in Kv4.3 augmentation between KChIP2.1 and KChIP2.2. The inactivation rate and recovery from inactivation were also altered by KChIP2 isoform co-expression. In contrast, hERG (Kv11.1) current was not altered by co-expression with KChIP2.1, KChIP2.2 or DPP6. NS3623 increased Kv4.3 amplitude to a similar extent with and without accessory subunit co-expression, however KChIP2 isoforms modulated the compound's effect on inactivation time course. The agonist effect of NS3623 on hERG channels was not affected by KChIP2.1, KChIP2.2 or DPP6 co-expression.

    Research areas

  • Heart, Action potential, potassium ion channels, transient outward current , hERG, KChIP2, DPP6, NS3623

Download statistics

No data available



  • Full-text PDF (final published version)

    Rights statement: This is the final published version of the article (version of record). It first appeared online via Elsevier at . Please refer to any applicable terms of use of the publisher.

    Final published version, 1.8 MB, PDF document

    Licence: CC BY


View research connections

Related faculties, schools or groups