From Atrial Small-conductance Calcium-activated Potassium Channels to New Antiarrhythmics.

European cardiology Pub Date : 2024-12-23 eCollection Date: 2024-01-01 DOI:10.15420/ecr.2024.41
Arnela Saljic, Jordi Heijman, Dobromir Dobrev
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Abstract

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 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.

Abstract Image

Abstract Image

从心房小导钙激活钾通道到新型抗心律失常药物。
尽管在其管理方面取得了重大进展,但房颤仍然是影响数百万人的主要医疗负担。使用抗心律失常药物或导管消融控制心律已被证明可改善房颤患者的症状和预后,但目前的治疗方案疗效有限和/或有明显的副作用。基于机制的新方法可能更有效,能够改善治疗AF的治疗策略。KCNN1-3编码的小电导钙活化钾(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引起了人们的兴趣。本文总结了小电导钙活化钾通道的分子组成及其在房颤中的复杂调控,以此作为理解孔阻滞剂(apamin, UCL1684, ICAGEN)和钙依赖性活化调节剂(NS8593, AP14145, AP30663)不同作用机制的基础。此外,对小电导钙活化钾通道抑制剂在房颤治疗中的作用的临床前和早期临床证据进行了综述。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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