ArticleProceedings of the National Academy of Sciences of the United States of America2003
The hSK4 (KCNN4) isoform is the Ca2+-activated K+ channel (Gardos channel) in human red blood cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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52 citing papers in PubMed, 133 citations in OpenAlex.
- Gardos channelopathies: novel insights into KCNN4 mutations and their clinical impact.Journal of human genetics · 2026Article
- Special Issue "Ion Conductance and Ion Regulation in Human Health and Disease".International journal of molecular sciences · 2025Article
- VX-445 (elexacaftor) inhibits chloride secretion across human bronchial epithelial cells by directly blocking KCa3.1 channels.PNAS nexus · 2025Article
- Design and structural basis of selective 1,4-dihydropyridine inhibitors of the calcium-activated potassium channel KProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Potassium dynamics in sickle cell anemia: clinical implications and pathophysiological insights.Annals of medicine and surgery (2012) · 2024Review
- Challenges in the Therapeutic Targeting of KCa Channels: From Basic Physiology to Clinical Applications.International journal of molecular sciences · 2024Review
- The Gárdos Channel and Piezo1 Revisited: Comparison between Reticulocytes and Mature Red Blood Cells.International journal of molecular sciences · 2024Article
- SARS-CoV-2 Impact on Red Blood Cell Morphology.Biomedicines · 2023Article
- The exocyst complex is required for the trafficking and delivery of KCa3.1 to the basolateral membrane of polarized epithelia.American journal of physiology. Cell physiology · 2023Article
- The circulatory dynamics of human red blood cell homeostasis: Oxy-deoxy and PIEZO1-triggered changes.Biophysical journal · 2023Article
- CaMolecules (Basel, Switzerland) · 2023Review
- Pharmacology of Small- and Intermediate-Conductance Calcium-Activated Potassium Channels.Annual review of pharmacology and toxicology · 2020Review
- Small and Intermediate Calcium Activated Potassium Channels in the Heart: Role and Strategies in the Treatment of Cardiovascular Diseases.Frontiers in physiology · 2020Review
- Possible New Strategies for the Treatment of Congenital Hyperinsulinism.Frontiers in endocrinology · 2020Article
- Ion Transport in Eryptosis, the Suicidal Death of Erythrocytes.Frontiers in cell and developmental biology · 2020Review
- The effect of the antisickling compound GBT1118 on the permeability of red blood cells from patients with sickle cell anemia.Physiological reports · 2019Article
- Activation mechanism of a human SK-calmodulin channel complex elucidated by cryo-EM structures.Science (New York, N.Y.) · 2018Article
- Evidence against a Role of Elevated Intracellular CaBiophysical journal · 2018Article
- Voltage-Activated Ion Channels in Non-excitable Cells-A Viewpoint Regarding Their Physiological Justification.Frontiers in physiology · 2018Article
- The Molecular Basis for Altered Cation Permeability in Hereditary Stomatocytic Human Red Blood Cells.Frontiers in physiology · 2018Review
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Authors and funding
6 authors at 3 institutions in 1 country.
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Abstract
The question is, does the isoform hSK4, also designated KCNN4, represent the small conductance, Ca2+-activated K+ channel (Gardos channel) in human red blood cells? We have analyzed human reticulocyte RNA by RT-PCR, and, of the four isoforms of SK channels known, only SK4 was found. Northern blot analysis of purified and synchronously growing human erythroid progenitor cells, differentiating from erythroblasts to reticulocytes, again showed only the presence of SK4. Western blot analysis, with an anti-SK4 antibody, showed that human erythroid progenitor cells and, importantly, mature human red blood cell ghost membranes, both expressed the SK4 protein. The Gardos channel is known to turn on, given inside Ca2+, in the presence but not the absence of external Ko+ and remains refractory to Ko+ added after exposure to inside Ca2+. Heterologously expressed SK4, but not SK3, also shows this behavior. In inside-out patches of red cell membranes, the open probability (Po) of the Gardos channel is markedly reduced when the temperature is raised from 27 to 37 degrees C. Net K+ efflux of intact red cells is also reduced by increasing temperature, as are the Po values of inside-out patches of Chinese hamster ovary cells expressing SK4 (but not SK3). Thus the envelope of evidence indicates that SK4 is the gene that codes for the Gardos channel in human red blood cells. This channel is important pathophysiologically, because it represents the major pathway for cell shrinkage via KCl and water loss that occurs in sickle cell disease.
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