Small-conductance calcium-activated potassium channel inhibitors are emerging as novel antiarrhythmic targets with potential atrial-predominant effects for the management of atrial fibrillation.
Small-conductance calcium-activated potassium channels represent a promising novel, atrial-predominant target for the development of new antiarrhythmic drugs for atrial fibrillation.
Despite significant advances in its management, AF remains a major healthcare burden affecting millions of individuals. Rhythm control with antiarrhythmic drugs or catheter ablation has been shown to improve symptoms and outcomes in AF patients, but current treatment options have limited efficacy and/or significant side-effects. Novel mechanism-based approaches could potentially be more effective, enabling improved therapeutic strategies for managing AF. Small-conductance calcium-activated potassium (SK or KCa2.x) channels encoded by KCNN1-3 have recently gathered interest as novel antiarrhythmic targets with potential atrial-predominant effects. Here, the molecular composition of small-conductance calcium-activated potassium channels and their complex regulation in AF as the basis for understanding the distinct mechanism of action of pore-blockers (apamin, UCL1684, ICAGEN) and modulators of calcium-dependent activation (NS8593, AP14145, AP30663) are summarised. Furthermore, the preclinical and early clinical evidence for the role of small-conductance calcium-activated potassium channel inhibitors in the treatment of AF are reviewed.
Saljic et al. (2024) conducted a review in Atrial Fibrillation. Small-conductance calcium-activated potassium channel inhibitors was evaluated. Small-conductance calcium-activated potassium channel inhibitors are emerging as novel antiarrhythmic targets with potential atrial-predominant effects for the management of atrial fibrillation.