AIMS: Pronounced sex-differences are known in the incidence of atrial fibrillation (AF). In this study, we aimed to investigate the atrial electrophysiological properties that may underlie sex-differences in AF incidence in the younger population, focusing on IK1, a cardiac ion current important for action potential (AP) stability and triggered activity. METHODS AND RESULTS: We assessed sex-differences in P-wave morphology in 12-lead ECG in healthy young New Zealand White rabbits. Males presented longer PWD and larger P-wave area compared to females. Patch-clamp experiments were performed in isolated rabbit atrial cardiomyocytes (CMs). Male atrial CMs presented higher delayed after depolarizations (DAD) incidence, amplitude, and area under the curve (AUC) than females, potentially facilitating the presence of atrial triggered activity in males. Male atrial CMs showed a less hyperpolarized resting membrane potential (RMP), a 50% smaller IK1, and a 26% reduction in Kir2.1 protein expression, a pore forming subunit of IK1, than females. Dihydrotestosterone (DHT) effects were investigated acutely and semi-chronically ex vivo. Experiments showed that the sex-difference in IK1 could be mimicked by DHT. In female atrial CMs, acute and semi-chronic (24â h) DHT administration reduced IK1. In the presence of a PKC-inhibitor, DHT-mediated IK1 reduction was not observed in atrial female CMs, suggesting it to be PKC-mediated. Chronic DHT-effects were investigated in vivo in female rabbits after hormone-releasing pellet implantation. After 2 weeks, animals showed a significantly prolonged and larger P-wave, a smaller atrial IK1 and a trend towards an increased DAD amplitude and AUC. CONCLUSION: Sex impacts on atrial electrophysiology, leading to sex-differences in P-wave morphology, triggered activity, RMP, and IK1. These sex-differences can be mimicked by sex hormone-treatment, suggesting that sex hormones-particularly DHT-play a pivotal role in mediating sex-differences in atrial electrophysiology. Such sex-differences might impact on the propensity to develop AF, particularly in the younger population.
Sex and sex hormonal regulation of the atrial inward rectifier potassium current (IK1): insights into potential pro-arrhythmic mechanisms.
阅读:3
作者:Giammarino Lucilla, Matas Lluis, Alerni Nicolò, Horváth András, Vashanthakumar Varjany, Nimani Saranda, Barbieri Miriam, Bains Sahej, Lopez Ruben, Louradour Julien, Ãrdög Balazs, Hof Thomas, Maguy Ange, Conte Giulio, Auricchio Angelo, Schotten Ulrich, Odening Katja E
期刊: | Cardiovascular Research | 影响因子: | 13.300 |
时间: | 2025 | 起止号: | 2025 Jul 31; 121(8):1215-1227 |
doi: | 10.1093/cvr/cvaf074 |
特别声明
1、本文转载旨在传播信息,不代表本网站观点,亦不对其内容的真实性承担责任。
2、其他媒体、网站或个人若从本网站转载使用,必须保留本网站注明的“来源”,并自行承担包括版权在内的相关法律责任。
3、如作者不希望本文被转载,或需洽谈转载稿费等事宜,请及时与本网站联系。
4、此外,如需投稿,也可通过邮箱info@biocloudy.com与我们取得联系。