Key result
SK channels offer promising atrial-selective targets for AF rhythm control despite context-dependent pro- and anti-arrhythmic effects.
Why the study?
Small-conductance Ca2+-activated K+ (SK) channels have emerged as promising atrial-selective targets for AF rhythm control, but structural and functional advances show context-dependent pro- and anti-arrhythmic effects.
Design
Mini review
Requires caution with SK channel modulators for AF rhythm control; extends recent structural insights but leaves open context-dependent net benefit.**[[1]](https://pubmed.ncbi.nlm.nih.gov/41849797/)[[2]](https://www.ecrjournal.
Small-conductance Ca²⁺-activated K⁺ (SK) channels have emerged as promising atrial-selective targets for rhythm control in atrial fibrillation (AF). Genetic association studies, functional experiments, and early clinical trials collectively support a role for SK channels in atrial repolarization and AF maintenance. Recent breakthroughs in single-particle cryo-electron microscopy have provided high-resolution structures of the SK2 channel, revealing unique architectural features that underlie its low conductance, and susceptibility to pharmacological modulation. Numerous studies have shown alterations in SK transcript abundance in AF in both humans and animal models. However, recent functional studies have demonstrated dynamic regulation of SK channel gating and membrane trafficking in AF, highlighting context-dependent pro- and anti-arrhythmic effects. This mini review summarizes the recent structural and functional advances in our understanding of SK channels, and emerging therapeutic implications for AF.
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McKie et al. (2026) studied this question. SK channels represent promising atrial-selective targets for atrial fibrillation rhythm control, although their dynamic regulation yields context-dependent pro- and anti-arrhythmic effects.
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