ArticleThe Journal of clinical investigation2007
Disruption of erythroid K-Cl cotransporters alters erythrocyte volume and partially rescues erythrocyte dehydration in SAD mice.
Article in The Journal of clinical investigation, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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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.
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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.
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Who cites it
48 citing papers in PubMed, 93 citations in OpenAlex.
- Sheep erythrocyte potassium locus highlights MYADM family regulation of electroneutral potassium chloride cotransporters (KCC).BMC genomics · 2026Article
- Spectrum of dominant Charcot-Marie-Tooth disease due toJournal of neurology, neurosurgery, and psychiatry · 2026Article
- The role ofJournal of pharmaceutical analysis · 2023Review
- Molecular mechanisms, physiological roles, and therapeutic implications of ion fluxes in bone cells: Emphasis on the cation-ClJournal of cellular physiology · 2022Review
- The erythroid K-Cl cotransport inhibitor [(dihydroindenyl)oxy]acetic acid blocks erythroid CaAmerican journal of physiology. Cell physiology · 2022Article
- Membrane transporters control cerebrospinal fluid formation independently of conventional osmosis to modulate intracranial pressure.Fluids and barriers of the CNS · 2022Article
- Erythroid-specific inactivation of Slc12a6/Kcc3 by EpoR promoter-driven Cre expression reduces K-Cl cotransport activity in mouse erythrocytes.Physiological reports · 2022Article
- The Important Role of Ion Transport System in Cervical Cancer.International journal of molecular sciences · 2021Review
- Article
- Advances in the development of novel compounds targeting cation-chloride cotransporter physiology.American journal of physiology. Cell physiology · 2021Review
- Distal convoluted tubule ClAmerican journal of physiology. Renal physiology · 2020Article
- Genetic disruption of KCC cotransporters in a mouse model of thalassemia intermedia.Blood cells, molecules & diseases · 2020Article
- Cryo-EM structures ofAmerican journal of physiology. Cell physiology · 2020Article
- Physiological Processes Modulated by the Chloride-Sensitive WNK-SPAK/OSR1 Kinase Signaling Pathway and the Cation-Coupled Chloride Cotransporters.Frontiers in physiology · 2020Review
- The role of WNK in modulation of KCl cotransport activity in red cells from normal individuals and patients with sickle cell anaemia.Pflugers Archiv : European journal of physiology · 2019Article
- Combined genetic disruption of K-Cl cotransporters and Gardos channel KCNN4 rescues erythrocyte dehydration in the SAD mouse model of sickle cell disease.Blood cells, molecules & diseases · 2019Article
- KJournal of hematology & oncology · 2019Review
- The WNK-SPAK/OSR1 Kinases and the Cation-Chloride Cotransporters as Therapeutic Targets for Neurological Diseases.Aging and disease · 2019Review
- Physiological roles and molecular mechanisms of KThe Journal of physiology · 2019Review
- Cotransporter-mediated water transport underlying cerebrospinal fluid formation.Nature communications · 2018Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
Abstract
K-Cl cotransport activity in rbc is a major determinant of rbc volume and density. Pathologic activation of erythroid K-Cl cotransport activity in sickle cell disease contributes to rbc dehydration and cell sickling. To address the roles of individual K-Cl cotransporter isoforms in rbc volume homeostasis, we disrupted the Kcc1 and Kcc3 genes in mice. As rbc K-Cl cotransport activity was undiminished in Kcc1(-/-) mice, decreased in Kcc3(-/-) mice, and almost completely abolished in mice lacking both isoforms, we conclude that K-Cl cotransport activity of mouse rbc is mediated largely by KCC3. Whereas rbc of either Kcc1(-/-) or Kcc3(-/-) mice were of normal density, rbc of Kcc1(-/-)Kcc3(-/-) mice exhibited defective volume regulation, including increased mean corpuscular volume, decreased density, and increased susceptibility to osmotic lysis. K-Cl cotransport activity was increased in rbc of SAD mice, which are transgenic for a hypersickling human hemoglobin S variant. Kcc1(-/-)Kcc3(-/-) SAD rbc lacked nearly all K-Cl cotransport activity and exhibited normalized values of mean corpuscular volume, corpuscular hemoglobin concentration mean, and K(+) content. Although disruption of K-Cl cotransport rescued the dehydration phenotype of most SAD rbc, the proportion of the densest red blood cell population remained unaffected.
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Registered trials
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