ArticleJournal of molecular and cellular cardiology2011
Loss of the AE3 anion exchanger in a hypertrophic cardiomyopathy model causes rapid decompensation and heart failure.
Article in Journal of molecular and cellular cardiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- Ablation of Slc26a6 Mitigates Myocardial Ischemia/Reperfusion Injury.Biomedicines · 2025Article
- Hypertrophic cardiomyopathy dysfunction mimicked in human engineered heart tissue and improved by sodium-glucose cotransporter 2 inhibitors.Cardiovascular research · 2024Article
- Potential Theranostic Roles of SLC4 Molecules in Human Diseases.International journal of molecular sciences · 2023Review
- The therapeutic importance of acid-base balance.Biochemical pharmacology · 2021Review
- Machine learning-based classification and diagnosis of clinical cardiomyopathies.Physiological genomics · 2020Article
- NBCe1 NaWorld journal of cardiology · 2018Article
- Mouse models of SLC4-linked disorders of HCOAmerican journal of physiology. Cell physiology · 2018Review
- Loss-of-activity-mutation in the cardiac chloride-bicarbonate exchanger AE3 causes short QT syndrome.Nature communications · 2017Article
- RNA SEQ Analysis Indicates that the AE3 ClScientific reports · 2017Article
- Investigation of SLA4A3 as a candidate gene for human retinal disease.Journal of negative results in biomedicine · 2016Article
- SERCA2 Haploinsufficiency in a Mouse Model of Darier Disease Causes a Selective Predisposition to Heart Failure.BioMed research international · 2015Article
- Critical role of bicarbonate and bicarbonate transporters in cardiac function.World journal of biological chemistry · 2014Review
- Molecular cloning and functional characterization of zebrafish Slc4a3/Ae3 anion exchanger.Pflugers Archiv : European journal of physiology · 2014Article
- Resistance to cardiomyocyte hypertrophy in ae3-/- mice, deficient in the AE3 Cl-/HCO3- exchanger.BMC cardiovascular disorders · 2014Article
- Loss of NHE1 activity leads to reduced oxidative stress in heart and mitigates high-fat diet-induced myocardial stress.Journal of molecular and cellular cardiology · 2013Article
- Decreasing tropomyosin phosphorylation rescues tropomyosin-induced familial hypertrophic cardiomyopathy.The Journal of biological chemistry · 2013Article
- Microarray analysis of active cardiac remodeling genes in a familial hypertrophic cardiomyopathy mouse model rescued by a phospholamban knockout.Physiological genomics · 2013Article
- Loss of the AE3 Cl(-)/HCO(-) 3 exchanger in mice affects rate-dependent inotropy and stress-related AKT signaling in heart.Frontiers in physiology · 2013Article
- Article
- Knockout of the Na,K-ATPase α₂-isoform in the cardiovascular system does not alter basal blood pressure but prevents ACTH-induced hypertension.American journal of physiology. Heart and circulatory physiology · 2011Article
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10 authors at 2 institutions in 1 country.
Funding
Abstract
The AE3 Cl(-)/HCO(3)(-) exchanger is abundantly expressed in the sarcolemma of cardiomyocytes, where it mediates Cl(-)-uptake and HCO(3)(-)-extrusion. Inhibition of AE3-mediated Cl(-)/HCO(3)(-) exchange has been suggested to protect against cardiac hypertrophy; however, other studies indicate that AE3 might be necessary for optimal cardiac function. To test these hypotheses we crossed AE3-null mice, which appear phenotypically normal, with a hypertrophic cardiomyopathy mouse model carrying a Glu180Gly mutation in α-tropomyosin (TM180). Loss of AE3 had no effect on hypertrophy; however, survival of TM180/AE3 double mutants was sharply reduced compared with TM180 single mutants. Analysis of cardiac performance revealed impaired cardiac function in TM180 and TM180/AE3 mutants. TM180/AE3 double mutants were more severely affected and exhibited little response to β-adrenergic stimulation, a likely consequence of their more rapid progression to heart failure. Increased expression of calmodulin-dependent kinase II and protein phosphatase 1 and differences in methylation and localization of protein phosphatase 2A were observed, but were similar in single and double mutants. Phosphorylation of phospholamban on Ser16 was sharply increased in both single and double mutants relative to wild-type hearts under basal conditions, leading to reduced reserve capacity for β-adrenergic stimulation of phospholamban phosphorylation. Imaging analysis of isolated myocytes revealed reductions in amplitude and decay of Ca(2+) transients in both mutants, with greater reductions in TM180/AE3 mutants, consistent with the greater severity of their heart failure phenotype. Thus, in the TM180 cardiomyopathy model, loss of AE3 had no apparent anti-hypertrophic effect and led to more rapid decompensation and heart failure.
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