Arrhythmias & electrophysiologyResearch article
Biophysical Characterization of a Novel KCNJ8 Rare Variant Linked With Inherited and Acquired J Wave Syndrome
- Biophysical characterization
- next-generation sequencing-based large gene panel
- whole-cell and inside-out patch-clamp
- homology models and molecular dynamics simulations
Authors' conclusion
Our findings demonstrate that the A88G mutant in KCNJ8 induces a gain-of-function in KATP current secondary to a major increase in open probability of the KATP channel responsible for increased channel conductance as well as a reduced sensitivity to inhibition of the channel by intracellular ATP. These findings provide further evidence pointing to KCNJ8 as a JWS and VF susceptibility gene.
Study context
- Population
- J-wave syndrome (JWS) probands and consecutive probands who developed ventricular fibrillation (VF) during acute myocardial infarctionJWS 413 · consecutive probands who developed VF during acute myocardial infarction 25
- Comparison
- KCNJ8-A88G compared with KCNJ8-WT
Main finding
As reported in the abstract
Carriers of KCNJ8 A88G
probands diagnosed with Brugada syndrome and/or early repolarization syndrome
3
Further findings
Conductance
P < 0.01
Open state duration (τ)
ATP IC50
P < 0.01
KATP current
- gain of function when KCNJ8-A88G was coexpressed with ABCC9-wide type (WT) compared with KCNJ8-WT
- 2-fold
Molecular dynamics
- A88G could release the restriction of residue F131, causing a greater separation of residues in the selectivity filter, resulting in increased channel conductance
Original publication
Biophysical Characterization of a Novel KCNJ8 Rare Variant Linked With Inherited and Acquired J Wave Syndrome. JACC Clin Electrophysiol. Published 16 April 2026. doi:10.1016/j.jacep.2026.02.005
Summarised from the published abstract; every number is checked against it