Pro-arrhythmic effects of gain-of-function potassium channel mutations in the short QT syndrome

Jules C Hancox, C Du, Andrew S Butler, Zhang Y, Christopher E Dempsey, Stephen C Harmer, H Zhang

Research output: Contribution to journalArticle (Academic Journal)peer-review

9 Citations (Scopus)


The congenital short QT syndrome (SQTS) is a rare condition characterized by abbreviated rate-corrected QT (QTc) intervals on the electrocardiogram and by increased susceptibility to both atrial and ventricular arrhythmias and sudden death. Although mutations to multiple genes have been implicated in the SQTS, evidence of causality is particularly strong for the first three (SQT1−3) variants: these result from gain-of-function mutations in genes that encode K+ channel subunits responsible, respectively, for the IKr, IKs and IK1 cardiac potassium currents. This article reviews evidence for the impact of SQT1-3 missense potassium channel gene mutations on the electrophysiological properties of IKr, IKs and IK1 and of the links between these changes and arrhythmia susceptibility. Data from experimental and simulation studies and future directions for research in this field are considered.
Original languageEnglish
Article number20220165
JournalPhilosophical Transactions B: Biological Sciences
Issue number1879
Publication statusPublished - 1 May 2023

Bibliographical note

Funding Information:
A.B. was supported by BHF FS/17/60/33474; Y.Z. was supported by BHF PG/21/10444; C.Y.D. was supported by PG/19/26/34302. Acknowledgements

Publisher Copyright:
© 2023 The Authors.


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