ArticleThe Journal of biological chemistry2008
Impaired cardiac contractility in mice lacking both the AE3 Cl-/HCO3- exchanger and the NKCC1 Na+-K+-2Cl- cotransporter: effects on Ca2+ handling and protein phosphatases.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 33 citations in OpenAlex.
- Exploring the Role of the SLC12A Cation-Coupled Chloride Cotransporters in the Cardiovascular System.Cells · 2026Review
- Ablation of Slc26a6 Mitigates Myocardial Ischemia/Reperfusion Injury.Biomedicines · 2025Article
- The Genetics and Epigenetics of Ventricular Arrhythmias in Patients Without Structural Heart Disease.Frontiers in cardiovascular medicine · 2022Review
- A Cardioplegic Solution with an Understanding of a Cardiochannelopathy.Antioxidants (Basel, Switzerland) · 2021Review
- 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
- Ablation of Potassium-Chloride Cotransporter Type 3 (Kcc3) in Mouse Causes Multiple Cardiovascular Defects and Isosmotic Polyuria.PloS one · 2016Article
- Critical role of the SPAK protein kinase CCT domain in controlling blood pressure.Human molecular genetics · 2015Article
- Regulation of vascular tone and arterial blood pressure: role of chloride transport in vascular smooth muscle.Pflugers Archiv : European journal of physiology · 2015Review
- 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
- 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
- K+-Cl- cotransporter-2 KCC2 in chicken cardiomyocytes.American journal of physiology. Cell physiology · 2012Article
- Article
- Loss of Slc4a1b chloride/bicarbonate exchanger function protects mechanosensory hair cells from aminoglycoside damage in the zebrafish mutant persephone.PLoS genetics · 2012Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
To analyze the cardiac functions of AE3, we disrupted its gene (Slc4a3) in mice. Cl(-)/HCO3(-) exchange coupled with Na+-dependent acid extrusion can mediate pH-neutral Na+ uptake, potentially affecting Ca2+ handling via effects on Na+/Ca2+ exchange. AE3 null mice appeared normal, however, and AE3 ablation had no effect on ischemia-reperfusion injury in isolated hearts or cardiac performance in vivo. The NKCC1 Na+-K+-2Cl(-) cotransporter also mediates Na+ uptake, and loss of NKCC1 alone does not impair contractility. To further stress the AE3-deficient myocardium, we combined the AE3 and NKCC1 knock-outs. Double knock-outs had impaired contraction and relaxation both in vivo and in isolated ventricular myocytes. Ca2+ transients revealed an apparent increase in Ca2+ clearance in double null cells. This was unlikely to result from increased Ca2+ sequestration, since the ratio of phosphorylated phospholamban to total phospholamban was sharply reduced in all three mutant hearts. Instead, Na+/Ca2+ exchanger activity was found to be enhanced in double null cells. Systolic Ca2+ was unaltered, however, suggesting more direct effects on the contractile apparatus of double null myocytes. Expression of the catalytic subunit of protein phosphatase 1 was increased in all mutant hearts. There was also a dramatic reversal, between single null and double null hearts, in the carboxymethylation and localization to the myofibrillar fraction, of the catalytic subunit of protein phosphatase 2A, which corresponded to the loss of normal contractility in double null hearts. These data show that AE3 and NKCC1 affect Ca2+ handling, PLN regulation, and expression and localization of major cardiac phosphatases and that their combined loss impairs cardiac function.
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