biostudies-literatureUnknown5(17)Jansen JIn 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 mBlood advances3303-3308https://www.ebi.ac.uk/biostudies/studies/S-EPMC8525243biostudies-literatureMechanistic ion channel interactions in red cells of patients with Gardos channelopathy.PMC8525243Hertz LKaestner LJansen JBianchi PWang XZaninoni AFermo EBernhardt IQiao MColombatti RfalseMechanistic ion channel interactions in red cells of patients with Gardos channelopathy.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 m2021-01-01T00:00:00Z2021 Sep2025-04-04T10:55:44.292Z2025-04-04T10:55:44.292ZS-EPMC85252433446872310.1182/bloodadvances.2020003823