ArticleProceedings of the National Academy of Sciences of the United States of America2007
Gene-trapped mouse embryonic stem cell-derived cardiac myocytes and human genetics implicate AKAP10 in heart rhythm regulation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 69 citations in OpenAlex.
- The evolution of AKAPs and emergence of PKA isotype selective anchoring determinants.The Journal of biological chemistry · 2025Article
- Nanodomain cAMP signaling in cardiac pathophysiology: potential for developing targeted therapeutic interventions.Physiological reviews · 2025Review
- The role of A-kinase anchoring proteins in cardiovascular diseases and recent advances.Frontiers in cell and developmental biology · 2025Review
- Identification of genetic association between mitochondrial dysfunction and knee osteoarthritis through integrating multi-omics: a summary data-based Mendelian randomization study.Clinical rheumatology · 2024Article
- AKAP12 Upregulation Associates With PDE8A to Accelerate Cardiac Dysfunction.Circulation research · 2024Article
- CaPhysiological reviews · 2024Review
- More evidence for widespread antagonistic pleiotropy in polymorphic disease alleles.Frontiers in genetics · 2024Review
- Compartmentalized cAMP signalling and control of cardiac rhythm.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Mitochondrial a Kinase Anchor Proteins in Cardiovascular Health and Disease: A Review Article on Behalf of the Working Group on Cellular and Molecular Biology of the Heart of the Italian Society of Cardiology.International journal of molecular sciences · 2022Review
- Aging Alters the Formation and Functionality of Signaling Microdomains Between L-type Calcium Channels and β2-Adrenergic Receptors in Cardiac Pacemaker Cells.Frontiers in physiology · 2022Article
- Review
- A-kinase-anchoring protein 1 (dAKAP1)-based signaling complexes coordinate local protein synthesis at the mitochondrial surface.The Journal of biological chemistry · 2020Article
- AKAP12 Signaling Complex: Impacts of Compartmentalizing cAMP-Dependent Signaling Pathways in the Heart and Various Signaling Systems.Journal of the American Heart Association · 2020Review
- Cardiac function modulation depends on the A-kinase anchoring protein complex.Journal of cellular and molecular medicine · 2019Review
- Single nucleotide polymorphisms alter kinase anchoring and the subcellular targeting of A-kinase anchoring proteins.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Roles of A-Kinase Anchoring Proteins and Phosphodiesterases in the Cardiovascular System.Journal of cardiovascular development and disease · 2018Review
- Polymorphisms/Mutations in A-Kinase Anchoring Proteins (AKAPs): Role in the Cardiovascular System.Journal of cardiovascular development and disease · 2018Review
- Functional Microdomains in Heart's Pacemaker: A Step Beyond Classical Electrophysiology and Remodeling.Frontiers in physiology · 2018Review
- Predisposition of functional genetic variants of A-kinase anchoring protein 10 toward acquired repolarization disorders in high-risk vascular surgery patients.Therapeutics and clinical risk management · 2018Article
- Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
Sudden cardiac death due to abnormal heart rhythm kills 400,000-460,000 Americans each year. To identify genes that regulate heart rhythm, we are developing a screen that uses mouse embryonic stem cells (mESCs) with gene disruptions that can be differentiated into cardiac cells for phenotyping. Here, we show that the heterozygous disruption of the Akap10 (D-AKAP2) gene that disrupts the final 51 aa increases the contractile response of cultured cardiac cells to cholinergic signals. In both heterozygous and homozygous mutant mice derived from these mESCs, the same Akap10 disruption increases the cardiac response to cholinergic signals, suggesting a dominant interfering effect of the Akap10 mutant allele. The mutant mice have cardiac arrhythmias and die prematurely. We also found that a common variant of AKAP10 in humans (646V, 40% of alleles) was associated with increased basal heart rate and decreased heart rate variability (markers of low cholinergic/vagus nerve sensitivity). These markers predict an increased risk of sudden cardiac death. Although the molecular mechanism remains unknown, our findings in mutant mESCs, mice, and a common human AKAP10 SNP all suggest a role for AKAP10 in heart rhythm control. Our stem cell-based screen may provide a means of identifying other genes that control heart rhythm.
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Registered trials
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.