ArticleScience advances2023
Whole-heart multiparametric optical imaging reveals sex-dependent heterogeneity in cAMP signaling and repolarization kinetics.
Article in Science advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 29 citations in OpenAlex.
- Uncovering a Sex-Specific cAMP Landscape in Vascular Smooth Muscle.bioRxiv : the preprint server for biology · 2026Article
- Prioritizing Discovery and Advancements in Arrhythmia Therapies: NIH/NHLBI Workshop.JACC. Clinical electrophysiology · 2026Review
- Multiparametric imaging of spatio-temporal cAMP signaling, transmembrane potential, and intracellular calcium in the intact heart.iScience · 2026Article
- Multiplexed Fiber-Optic Fluorescence for Functional Monitoring of Perfused Hearts.Analytical chemistry · 2025Article
- Autonomic imbalance in cardiovascular disease: molecular mechanisms and emerging therapeutics.American journal of physiology. Cell physiology · 2025Review
- Targeted protein degradation of PDE4 shortforms by a novel proteolysis targeting chimera.The FEBS journal · 2025Article
- Nanodomain cAMP signaling in cardiac pathophysiology: potential for developing targeted therapeutic interventions.Physiological reviews · 2025Review
- Molecular and cellular neurocardiology in heart disease.The Journal of physiology · 2025Review
- A soft multimodal optoelectronic array interface for multiparametric mapping of heart function in vivo.Science advances · 2025Article
- Cardiac Gene Therapy With Phosphodiesterase 2A Limits Remodeling and Arrhythmias in Mouse Models of Heart Failure.Journal of the American Heart Association · 2025Article
- Enhanced CaJACC. Clinical electrophysiology · 2024Article
- Sympathetic structural and electrophysiological remodeling in a rabbit model of reperfused myocardial infarction.American journal of physiology. Heart and circulatory physiology · 2024Article
- Chronic nicotine exposure is associated with electrophysiological and sympathetic remodeling in the intact rabbit heart.American journal of physiology. Heart and circulatory physiology · 2024Article
- Evaluation of novel open-source software for cardiac optical mapping.Journal of molecular and cellular cardiology plus · 2024Article
- Phosphodiesterase in heart and vessels: from physiology to diseases.Physiological reviews · 2024Review
- Optical mapping and optogenetics in cardiac electrophysiology research and therapy: a state-of-the-art review.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2024Review
- cAMP-PKA/EPAC signaling and cancer: the interplay in tumor microenvironment.Journal of hematology & oncology · 2024Review
- Compartmentalized cAMP signalling and control of cardiac rhythm.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Cyclic adenosine 3',5'-monophosphate (cAMP) is a key second messenger in cardiomyocytes responsible for transducing autonomic signals into downstream electrophysiological responses. Previous studies have shown intracellular heterogeneity and compartmentalization of cAMP signaling. However, whether cAMP signaling occurs heterogeneously throughout the intact heart and how this drives sex-dependent functional responses are unknown. Here, we developed and validated a novel cardiac-specific fluorescence resonance energy transfer-based cAMP reporter mouse and a combined voltage-cAMP whole-heart imaging system. We showed that in male hearts, cAMP was uniformly activated in response to pharmacological β-adrenergic stimulation. In contrast, female hearts showed that cAMP levels decayed faster in apical versus basal regions, which was associated with nonuniform action potential changes and notable changes in the direction of repolarization. Apical phosphodiesterase (PDE) activity was higher in female versus male hearts, and PDE inhibition prevented repolarization changes in female hearts. Thus, our imaging approach revealed sex-dependent regional breakdown of cAMP and associated electrophysiological differences.
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