Evidence map›Paper›PMID 40272446›Full record

ArticleCardiovascular research2025

Sex and sex hormonal regulation of the atrial inward rectifier potassium current (IK1): insights into potential pro-arrhythmic mechanisms.

Lucilla Giammarino, Lluis Matas, Nicolò Alerni, András Horváth, Varjany Vashanthakumar, Saranda Nimani, Miriam Barbieri, Sahej Bains, Ruben Lopez, Julien Louradour and 7 more

Abstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Cardiovascular research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Review
  2. Article
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  5. Review
  6. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

Lucilla GiammarinoTranslational Cardiology, Department of Physiology and Department of Cardiology, University of Bern, University Hospital Bern, Bühlplatz 5, Bern 3012, Switzerland.ORCID 0000-0002-2100-0160
Lluis MatasTranslational Cardiology, Department of Physiology and Department of Cardiology, University of Bern, University Hospital Bern, Bühlplatz 5, Bern 3012, Switzerland.
Nicolò AlerniTranslational Cardiology, Department of Physiology and Department of Cardiology, University of Bern, University Hospital Bern, Bühlplatz 5, Bern 3012, Switzerland.
András HorváthTranslational Cardiology, Department of Physiology and Department of Cardiology, University of Bern, University Hospital Bern, Bühlplatz 5, Bern 3012, Switzerland.
Varjany VashanthakumarTranslational Cardiology, Department of Physiology and Department of Cardiology, University of Bern, University Hospital Bern, Bühlplatz 5, Bern 3012, Switzerland.
Saranda NimaniTranslational Cardiology, Department of Physiology and Department of Cardiology, University of Bern, University Hospital Bern, Bühlplatz 5, Bern 3012, Switzerland.
Miriam BarbieriTranslational Cardiology, Department of Physiology and Department of Cardiology, University of Bern, University Hospital Bern, Bühlplatz 5, Bern 3012, Switzerland.
Sahej BainsDepartments of Cardiovascular Medicine, Pediatric and Adolescent Medicine, and Molecular Pharmacology and Experimental Therapeutics, Divisions of Heart Rhythm Services and Pediatric Cardiology, Windland Smith Rice Genetic Heart Rhythm Clinic and the Windland Smith Rice Sudden Death Genomics Laboratory, Mayo Clinic, Rochester, USA.
Ruben LopezTranslational Cardiology, Department of Physiology and Department of Cardiology, University of Bern, University Hospital Bern, Bühlplatz 5, Bern 3012, Switzerland.
Julien LouradourTranslational Cardiology, Department of Physiology and Department of Cardiology, University of Bern, University Hospital Bern, Bühlplatz 5, Bern 3012, Switzerland.
Balazs ÖrdögTranslational Cardiology, Department of Physiology and Department of Cardiology, University of Bern, University Hospital Bern, Bühlplatz 5, Bern 3012, Switzerland.
Thomas HofTranslational Cardiology, Department of Physiology and Department of Cardiology, University of Bern, University Hospital Bern, Bühlplatz 5, Bern 3012, Switzerland.
Ange MaguyDepartment of Physiology, University of Bern, Bern, Switzerland.
Giulio ConteDepartment of Cardiology, Cardiocentro Ticino Institute, Ente Ospedaliero Cantonale, Lugano, Switzerland.
Angelo AuricchioDepartment of Cardiology, Cardiocentro Ticino Institute, Ente Ospedaliero Cantonale, Lugano, Switzerland.ORCID 0000-0003-2116-6993
Ulrich SchottenDepartment of Physiology, Maastricht University, Maastricht, The Netherlands.ORCID 0000-0003-1532-3315
Katja E OdeningTranslational Cardiology, Department of Physiology and Department of Cardiology, University of Bern, University Hospital Bern, Bühlplatz 5, Bern 3012, Switzerland.ORCID 0000-0001-6999-841X

Funding

EmbRACE: Electro-Molecular BasisEuropean Union 965286Netherlands Heart Foundation 01-002-2022-0118Rapeutic management of Atrial CardiomyopathySwiss Heart Foundation FF20042
6 · The paper itself

Abstract

aimsPronounced 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

resultsWe 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 (24 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.

conclusionSex 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.

Indexed as

Action PotentialsAtrial FibrillationGonadal Steroid HormonesHeart AtriaHeart RateMyocytes, CardiacPotassium Channels, Inwardly RectifyingAnimalsDihydrotestosteroneFemaleMaleRabbitsSex FactorsDihydrotestosteroneGonadal Steroid HormonesKir2.1 channelPotassium Channels, Inwardly RectifyingAtrial fibrillationIK1Sex differencesSex hormones

Identifiers

PMID40272446
PMCPMC12310280

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.