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Molecular and Cellular Biochemistry

, Volume 436, Issue 1–2, pp 71–78 | Cite as

Corticosteroids and aldose reductase inhibitor Epalrestat modulates cardiac action potential via Kvβ1.1 (AKR6A8) subunit of voltage-gated potassium channel

  • Jared Tur
  • Sachin L. Badole
  • Feng Cheng
  • Aparoop Das
  • Rakesh C. Kukreja
  • Srinivas M. Tipparaju
Article
  • 181 Downloads

Abstract

We previously demonstrated the role of Kvβ1.1 subunit of voltage-activated potassium channel in heart for its sensory roles in detecting changes in NADH/NAD and modulation of ion channel. However, the pharmacological role for the association of Kvβ1 via its binding to ligands such as cortisone and its analogs remains unknown. Therefore, we investigated the significance of Kvβ1.1 binding to cortisone analogs and AR inhibitor epalrestat. In addition, the aldose reductase (AR) inhibitor epalrestat was identified as a pharmacological target and modulator of cardiac activity via binding to the Kvβ1 subunit. Using a combination of ex vivo cardiac electrophysiology and in silico binding, we identified that Kvβ1 subunit binds and interacts with epalrestat. To identify the specificity of the action potential changes, we studied the sensitivity of the action potential prolongation by probing the electrical changes in the presence of 4-aminopyridine and evaluated the specificity of pharmacological effects in the hearts from Kvβ1.1 knock out mouse. Our results show that pharmacological modulation of cardiac electrical activity by cortisone analogs and epalrestat is mediated by Kvβ1.1.

Keywords

Kvβ subunit Heart Aldo–keto reductase Cortisone 

Notes

Acknowledgements

Funding

Authors acknowledge the grant support received from NIH HL102171 to (SMT).

Compliance with ethical standards

Disclosures

Authors have no disclosures.

Ethical approval

All institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the Institutional Animal Care and Use Committee at the University of South Florida (Tampa, FL, USA) at which the studies were conducted.

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Jared Tur
    • 1
  • Sachin L. Badole
    • 1
  • Feng Cheng
    • 1
  • Aparoop Das
    • 2
  • Rakesh C. Kukreja
    • 3
  • Srinivas M. Tipparaju
    • 1
  1. 1.Department of Pharmaceutical Sciences, College of PharmacyUniversity of South FloridaTampaUSA
  2. 2.Department of Pharmaceutical SciencesDibrugarh UniversityDibrugarhIndia
  3. 3.Pauley Heart Center, Department of MedicineVirginia Commonwealth UniversityRichmondUSA

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