Arrhythmias & electrophysiology
C-terminal long-QT type 1 R562S-Kv7.1 variant, the first variant in helix C impairing β-adrenergic response of the slow delayed rectifier K+ channel
Authors' conclusion
R562S-Kv7.1 is the first variant in helix C causing an impaired response of IKs channel to β-adrenergic stimulation, likely due to altered interactions between channel subunits, namely Kv7.1 and KCNE1.
Study context
- Population
- Four putatively unrelated families in the Czech Republic carrying the LQT1 R562S-Kv7.1 variantfour families
- Comparison
- R562S-Kv7.1 carriers vs healthy relatives; R562S vs wild-type IKs channels
Methodological detailsClinical and genetic investigation, then functional analysis (whole-cell patch clamp, confocal microscopy, computational simulations) and structural modelling
- Clinical and genetic investigation, then functional analysis (whole-cell patch clamp, confocal microscopy, computational simulations) and structural modelling
Main finding
As reported in the abstract
- Significantly prolonged QTc at rest in R562S carriers vs healthy relatives
- Significantly higher QTc prolongation after exercise in R562S carriers vs healthy relatives
- R562S channels: preserved membrane localisation
- R562S channels: significant decrease in IKs with rightward shift of voltage dependence of activation
- R562S channels: lack of responsiveness to β-adrenergic stimulation, seemingly related to modified KCNE1–Kv7.1 interaction
- Pro-arrhythmic DADs during β-adrenergic stimulation effectively prevented by mild (5%) ICa inhibition (simulation)
Further findings
Genetic analysis
- R562S-Kv7.1 might be a founder LQT1 variant in Central Europe
Original publication
C-terminal long-QT type 1 R562S-Kv7.1 variant, the first variant in helix C impairing β-adrenergic response of the slow delayed rectifier K+ channel. Europace. Published 18 June 2026. doi:10.
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