HCN4 Mutation Causing Familial Inappropriate Sinus Tachycardia Leads to a Conformational Change Mimicking cAMP Binding and Induces Constitutive Channel Activity
We identified a gain-of-function <i>HCN4</i> variant in a family with IST that displays constitutive activity and structurally mimics the effects of cAMP activation. This study furthers our understanding of the mechanisms underlying IST and provides data supporting the efficacious effect of ivabradine in genetically based IST.
Authors
- Íñigo Marcos‐Alcalde (ORCID: https://orcid.org/0000-0002-0674-6423)
- Michael H. Gollob (ORCID: https://orcid.org/0000-0003-0242-5208)
- Trent Faultless (ORCID: https://orcid.org/0000-0001-5172-3442)
- Paulino Gómez‐Puertas (ORCID: https://orcid.org/0000-0003-3131-729X)
- David Ros‐Pardo (ORCID: https://orcid.org/0000-0002-8934-8585)
- Sara L. Bober (ORCID: https://orcid.org/0009-0002-4063-5935)
- Qiuju Li (ORCID: https://orcid.org/0000-0001-8627-6494)
Institutions
- University of Toronto (CA)
- Hamilton General Hospital (CA)
- Centro de Biología Molecular Severo Ochoa (ES)
- Universidad Autónoma de Madrid (ES)
Publication Details
- Journal
- Circulation Arrhythmia and Electrophysiology
- Published
- 2025-10-14
- DOI
- https://doi.org/10.1161/circep.125.013899
- Primary Topic
- Cardiac electrophysiology and arrhythmias
- Type
- article
- Field-Weighted Citation Impact
- 0.00