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Ion Channels in Immune Cells
Published in Shyam S. Bansal, Immune Cells, Inflammation, and Cardiovascular Diseases, 2022
Devasena Ponnalagu, Shridhar Sanghvi, Shyam S. Bansal, Harpreet Singh
KCa channels comprise the small conductance (SKCa, ~10 pS), the intermediate conductance (IKCa, ~40 pS), and the large conductance (BKCa, ~300 pS) K+ channels93. The KCa3.1 (also known as IKCa, KCNN4, Gardos channel, KCa3.1, and human SK4) currents were first observed in erythrocytes in which it was shown to be important for cell-volume regulation93,94. Later on, KCa3.1 was observed in many of the immune cells12,65,95–97.
Secreted effectors of the innate mucosal barrier
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
Michael A. McGuckin, Andre J. Ouellette, Gary D. Wu
Paneth cells release secretory granules in a dose-dependent manner in response to bacterial antigens and pharmacologic agents. Paneth cell secretion induced by bacterial and carbamyl choline antigens is regulated by cytosolic Ca2+ mobilized from intracellular stores and an influx of extracellular Ca2+. Inhibiting influx of Ca2+ by selective blockers of the Ca2+-activated intermediate conductance K+ channel KCa3.1 (also known as Kcnn4 and mIKCa1) attenuates Paneth cell secretion. KCa3.1 is expressed in Paneth cells and T lymphocytes, and enables Ca2+ influx to sustain the Paneth cell secretory response. However, whether defects in KCa3.1 impair Paneth cell secretion sufficiently to diminish levels of luminal α-defensins and other secreted components in vivo is not known.
Liver Disease in Cystic Fibrosis
Published in Gianfranco Alpini, Domenico Alvaro, Marco Marzioni, Gene LeSage, Nicholas LaRusso, The Pathophysiology of Biliary Epithelia, 2020
Carla Colombo, Pier Maria Battezzati, Clara Fredella, Andrea Crosignani
In our cohort incidence of liver disease was significantly higher in patients with a positive history of meconium ileus, most of whom had developed liver disease within the first decade of life. This association, linking inspissated gut content and biliary secretions, was firstly described by a necropsy study,23 but has not been consistendy found in cross-sectional studies involving different populations of CF patients.30 In patients with positive history of meconium ileus, additional risk factors for development of liver disease may include extensive abdominal surgery and prolonged total parenteral nutrition.45 A number of still unknown factors, including genetic modifiers associated with gender or ethnic group, may confer patients different susceptibility to liver involvement. The existence of a modifier locus for meconium ileus (CFM1) on human chromosome 19q13.2 has been recently reported46 and a potential candidate is the KCNN4 gene encoding for a Ca2+ activated medium conductance potassium channel, which could be implicated in modifying an alternative chloride secretion in the intestine. This or other genetic modifiers may modulate both the hepatic and intestinal manifestations of CF through strictly gastrointestinal mechanisms.
Why do platelets express K+ channels?
Published in Platelets, 2021
Joy R Wright, Martyn P. Mahaut-Smith
KCa3.1 (gene name KCNN4), also known as the Gardos channel and SK4, is a K+ selective ion channel activated by an increase in intracellular Ca2+. The channel is not activated by voltage at resting levels of Ca2+ and at elevated Ca2+ levels displays only minor increases in open probability in response to large depolarizations. It is often referred to as the intermediate conductance KCa channel due to the relative size of its single-channel conductance compared with other classes of Ca2+-activated K+ channel. Structurally, the channel consists of four identical subunits with each subunit comprising six transmembrane domains and a pore-forming domain [22]. Patch clamp experiments suggest that platelets express only a small number of functional KCa3.1 channels, around 5–7 per platelet [10], which may explain why the channel was not detected during transcriptomic screening of the platelet ion channelome [2]. The channel was first characterized in erythrocytes where it plays an important role in volume regulation [23].
Unifying heterogeneous expression data to predict targets for CAR-T cell therapy
Published in OncoImmunology, 2021
Patrick Schreiner, Mireya Paulina Velasquez, Stephen Gottschalk, Jinghui Zhang, Yiping Fan
We identified two novel, potentially suitable cancer-testis antigens, PRSS21 and PRAME, in pediatric AMKL which have a similar expression profile to successfully targeted antigens using CAR-T cell therapy. These genes were overexpressed in primary tumor samples from patients with AMKL, and their RNA and protein expression was almost exclusively limited to testes in normal tissues.28 Therapies targeting cancer/testis antigens have demonstrated anti-tumor efficacy.29 Previous research supports that PRSS21 and PRAME are targetable antigens on the plasma membrane.68,69 Both PRSS21 and PRAME have been associated with tumor progression in testicular tumors and melanomas, respectively, which may explain their AMKL-specific presence.70 Further, PRAME is known to be recognized by cytolytic T lymphocytes, which is a critical checkpoint in defining antigen potential in CAR-T therapy.71 Another candidate identified by our algorithm that has proven therapeutic success, potassium-activated channel KCNN4, is currently a Food and Drug Administration–approved drug target in sickle cell anemia.72
Inhibitory effects of candesartan on KCa3.1 potassium channel expression and cell culture and proliferation in peripheral blood CD4+T lymphocytes in Kazakh patients with hypertension from the Xinjiang region
Published in Clinical and Experimental Hypertension, 2018
Hui Li, Jun-Ling Zhao, Yuan-Ming Zhang, Su-Xia Han
The intermediate conductance Ca2+-activated K+ channel, KCa3.1 (KCNN4) was cloned independently by three groups in 1997 from pancreas, placenta, and lymph nodes (18). KCa3.1 is widely expressed in immune system cells such as T and B lymphocytes (19,20), mast cells, macrophages, and microglia, where it plays an important role in cellular activation, migration, and cytokine production (21).