Pharmacological Enhancement of Small Conductance Ca <sup>2+</sup> -Activated K <sup>+</sup> Channels Suppresses Cardiac Arrhythmias in a Mouse Model of Catecholaminergic Polymorphic Ventricular Tachycardia
Sarcolemmal SK channel enhancement reduces arrhythmic potential by restoring repolarization force in CPVT VMs. Activation of mitochondrial SK channels attenuates mitochondria structural changes in CPVT, restoring more efficient electron transport chain assembly into supercomplexes and reducing mito-reactive oxygen species production. This decreases RyR2 oxidation and thus channel activity, reducing spontaneous Ca<sup>2+</sup> waves underlying arrhythmogenic delayed afterdepolarizations.
Authors
- Sándor Györke (ORCID: https://orcid.org/0000-0002-0821-1983)
- Anastasia Pokrass
- Radmila Terentyeva (ORCID: https://orcid.org/0000-0002-0133-3515)
- Shanna Hamilton (ORCID: https://orcid.org/0000-0003-1016-4706)
- Fruzsina Perger
- Snizhana Chorna
- Isabelle Deschênes (ORCID: https://orcid.org/0000-0002-1812-7267)
- Zuzana Nichtová (ORCID: https://orcid.org/0000-0001-7358-3268)
- Andriy E. Belevych (ORCID: https://orcid.org/0000-0002-1272-5784)
- György Csordás (ORCID: https://orcid.org/0000-0003-3156-1460)
- Harpreet Singh (ORCID: https://orcid.org/0000-0002-6135-1897)
- Björn C. Knollmann (ORCID: https://orcid.org/0000-0003-4956-9735)
- Dmitry Terentyev (ORCID: https://orcid.org/0000-0002-9530-7384)
- Bin Liu (ORCID: https://orcid.org/0000-0003-4797-8105)
- Yujia Cheng (ORCID: https://orcid.org/0009-0006-8688-5269)
- Roland Veress (ORCID: https://orcid.org/0000-0001-8733-7228)
- Richard Clements
Institutions
- University of Arizona (US)
- Thomas Jefferson University (US)
- University of Rhode Island (US)
- Brown University (US)
- Providence VA Medical Center (US)
- The Ohio State University Wexner Medical Center (US)
- University of Florida (US)
- The Ohio State University (US)
- Vanderbilt University Medical Center (US)
Publication Details
- Journal
- Circulation Research
- Published
- 2025-05-29
- DOI
- https://doi.org/10.1161/circresaha.124.325477
- Citations
- 4
- Primary Topic
- Cardiac electrophysiology and arrhythmias
- Type
- article
- Field-Weighted Citation Impact
- 5.55