Saljic Arnela, Heijman Jordi, Dobrev Dobromir
Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen Copenhagen, Denmark.
Institute of Pharmacology, West German Heart and Vascular Center, University of Duisburg-Essen Essen, Germany.
Eur Cardiol. 2024 Dec 23;19:e26. doi: 10.15420/ecr.2024.41. eCollection 2024.
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 have recently gathered interest as novel antiarrhythmic targets with potential atrial-predominant effects. Here, the molecular composition of smallconductance 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.
尽管房颤的管理取得了显著进展，但它仍然是影响数百万人的主要医疗负担。抗心律失常药物或导管消融的节律控制已被证明可改善房颤患者的症状和预后，但目前的治疗选择疗效有限和/或有明显副作用。基于新机制的方法可能更有效，从而能够改进房颤管理的治疗策略。由 编码的小电导钙激活钾（SK或KCa2.x）通道最近作为具有潜在心房优势效应的新型抗心律失常靶点而受到关注。在此，总结了小电导钙激活钾通道的分子组成及其在房颤中的复杂调节，作为理解孔道阻滞剂（蜂毒明肽、UCL1684、ICAGEN）和钙依赖性激活调节剂（NS8593、AP14145、AP30663）不同作用机制的基础。此外，还综述了小电导钙激活钾通道抑制剂在房颤治疗中作用的临床前和早期临床证据。
