ArticleBlood advances2021
Mechanistic ion channel interactions in red cells of patients with Gárdos channelopathy.
Article in Blood advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 20 citations in OpenAlex.
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- Gardos channelopathies: novel insights into KCNN4 mutations and their clinical impact.Journal of human genetics · 2026Article
- Mechanistic Consequences of Piezo1 Gain-of-Function Variants for Decreased Red Cell Survival in Hereditary Xerocytosis.American journal of hematology · 2026Article
- Mechanotransduction mechanisms in human erythrocytes: Fundamental physiology and clinical significance.Channels (Austin, Tex.) · 2025Review
- Piezo1 Channel Activators Yoda1 and Yoda2 in the Context of Red Blood Cells.Biomolecules · 2025Article
- Increased activity of Piezo1 channel in red blood cells is associated with Alzheimer's disease-related dementia.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Sodium-Selective Channelrhodopsins.Cells · 2024Review
- Erythrocytes membrane fluidity changes induced by adenylyl cyclase cascade activation: study using fluorescence recovery after photobleaching.European biophysics journal : EBJ · 2024Article
- The Gárdos Channel and Piezo1 Revisited: Comparison between Reticulocytes and Mature Red Blood Cells.International journal of molecular sciences · 2024Article
- Evidence of in vivo exogen protein uptake by red blood cells: a putative therapeutic concept.Blood advances · 2023Article
- Dual action of Dooku1 on PIEZO1 channel in human red blood cells.Frontiers in physiology · 2023Article
- Deregulated calcium signaling in blood cancer: Underlying mechanisms and therapeutic potential.Frontiers in oncology · 2022Review
- The Function of Ion Channels and Membrane Potential in Red Blood Cells: Toward a Systematic Analysis of the Erythroid Channelome.Frontiers in physiology · 2022Article
- Article
- The Chloride Conductance Inhibitor NS3623 Enhances the Activity of a Non-selective Cation Channel in Hyperpolarizing Conditions.Frontiers in physiology · 2021Article
- The Transient Receptor Potential Vanilloid Type 2 (TRPV2) Channel-A New Druggable CaFrontiers in physiology · 2021Article
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In patients with Gárdos channelopathy (p.R352H), an increased concentration of intracellular Ca2+ was previously reported. This is a surprising finding because the Gárdos channel (KCa3.1) is a K+ channel. Here, we confirm the increased intracellular Ca2+ for patients with the KCa3.1 mutation p.S314P. Furthermore, we provide the concept of KCa3.1 activity resulting in a flickering of red blood cell (RBC) membranepotential, which activates the CaV2.1 channel allowing Ca2+ to enter the RBC. Activity of the nonselective cation channel Piezo1 modulates the aforementioned interplay in away that a closed Piezo1 is in favor of the KCa3.1-CaV2.1 interaction. In contrast, Piezo1 openings compromise the membrane potential flickering, thus limiting the activity of CaV2.1. With the compound NS309, we mimic a gain-of-function mutation of KCa3.1. Assessing the RBC Ca2+ response by Fluo-4-based flow cytometry and by measuring the membrane potential using the Macey-Bennekou-Egée method, we provide data that support the concept of the KCa3.1/CaV2.1/Piezo1 interplay as a partial explanation for an increased number of high Ca2+ RBCs. With the pharmacological inhibition of KCa3.1 (TRAM34 and Senicapoc), CaV2.1 (ω-agatoxin TK), and Piezo1 (GsMTx-4), we could project the NS309 behavior of healthy RBCs to the RBCs of Gárdos channelopathy patients.
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