cDNA Cloning and Functional Characterization of the Mouse Ca2+-gated K+ Channel, mIK1

We have cloned from murine erythroleukemia (MEL) cells, thymus, and stomach the cDNA encoding the Ca2+-gated K+ (KCa) channel, mIK1, the mouse homolog of hIK1 (Ishii, T. M., Silvia, C., Hirschberg, B., Bond, C. T., Adelman, J. P., and Maylie, J. (1997) Proc. Natl. Acad. Sci.(U. S. A. 94, 11651–11656). mIK1 mRNA was detected at varied levels in many tissue types. mIK1 KCa channel activity expressed inXenopus oocytes closely resembled the Kca of red cells (Gardos channel) and MEL cells in its single channel conductance, lack of voltage-sensitivity of activation, inward rectification, and Ca2+ concentration dependence. mIK1 also resembled the erythroid channel in its pharmacological properties, mediating whole cell and unitary currents sensitive to low nm concentrations of both clotrimazole (CLT) and its des-imidazolyl metabolite, 2-chlorophenyl-bisphenyl-methanol, and to low nm concentrations of iodocharybdotoxin. Whereas control oocytes subjected to hypotonic swelling remained swollen, mIK1 expression conferred on oocytes a novel, Ca2+-dependent, CLT-sensitive regulatory volume decrease response. Hypotonic swelling of voltage-clamped mIK1-expressing oocytes increased outward currents that were Ca2+-dependent, CLT-sensitive, and reversed near the K+ equilibrium potential. mIK1 mRNA levels in ES cells increased steadily during erythroid differentiation in culture, in contrast to other KCa mRNAs examined. Low nanomolar concentrations of CLT inhibited proliferation and erythroid differentiation of peripheral blood stem cells in liquid culture.

• Publication year

  1998

• Venue

  Journal of Biological Chemistry

• Publication date

  1998-08-21

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1074/jbc.273.34.21542PMID 9705284
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Ca2+-Activated K+ channel from human erythrocyte membranes: Single channel recification and selectivity

  2005cited by this paper
• Ca2+-activated K+ permeability in human erythrocytes: Modulation of single-channel events

  2004cited by this paper
• Characteristics of rabbit ClC-2 current expressed in Xenopus oocytes and its contribution to volume regulation.

  1998cited by this paper
• Characteristics of rabbit ClC-2 current expressed in Xenopus oocytes and its contribution to volume regulation.

  1998cited by this paper
• A human intermediate conductance calcium-activated potassium channel.

  1997cited by this paper
• Erythrocyte membrane transport physiology

  1997cited by this paper
• Inhibition of intestinal Cl- secretion by clotrimazole: direct effect on basolateral membrane K+ channels.

  1997cited by this paper
• A Novel Gene, hKCa4, Encodes the Calcium-activated Potassium Channel in Human T Lymphocytes*

  1997cited by this paper
• The Antifungal Imidazole Clotrimazole and its Major In Vivo Metabolite are Potent Blockers of the Calcium-Activated Potassium Channel in Murine Erythroleukemia Cells

  1997cited by this paper
• Functional consequences of mutations in the transmembrane domain and the carboxy-terminus of the murine AE1 anion exchanger.

  1997cited by this paper
• A common precursor for primitive erythropoiesis and definitive haematopoiesis

  1997cited by this paper
• hSK4, a member of a novel subfamily of calcium-activated potassium channels.

  1997cited by this paper
• Electrogenic Sulfate/Chloride Exchange in Xenopus Oocytes Mediated by Murine AE1 E699Q

  1997cited by this paper
• Secondary regulatory volume increase conferred on Xenopus oocytes by expression of AE2 anion exchanger.

  1997cited by this paper
• Oral magnesium supplements reduce erythrocyte dehydration in patients with sickle cell disease.

  1997cited by this paper
• Pathogenesis and treatment of sickle cell disease.

  1997cited by this paper
• The antifungal antibiotic, clotrimazole, inhibits chloride secretion by human intestinal T84 cells via blockade of distinct basolateral K+ conductances. Demonstration of efficacy in intact rabbit colon and in an in vivo mouse model of cholera.

  1997cited by this paper
• Mapping the Ends of Transmembrane Segments in a Polytopic Membrane Protein

  1997cited by this paper
• K+ channel antisense oligodeoxynucleotides inhibit cytokine-induced expansion of human hemopoietic progenitors

  1996cited by this paper
• Effects of cytochrome P-450 inhibitors on ionic currents in isolated rat type I carotid body cells.

  1996cited by this paper
• Voltage-gated K+ Channels Contain Multiple Intersubunit Association Sites*

  1996cited by this paper
• Activation of different Cl currents in Xenopus oocytes by Ca liberated from stores and by capacitative Ca influx

  1996cited by this paper
• Small-Conductance, Calcium-Activated Potassium Channels from Mammalian Brain

  1996cited by this paper
• Dehydration of transferrin receptor-positive sickle reticulocytes during continuous or cyclic deoxygenation: role of KCl cotransport and extracellular calcium.

  1996cited by this paper
• The antifungal antibiotic, clotrimazole, inhibits Cl- secretion by polarized monolayers of human colonic epithelial cells.

  1996cited by this paper
• PDZs and receptor/channel clustering: rounding up the latest suspects.

  1996cited by this paper
• Targeted disruption of guanosine diphosphate-dissociation inhibitor for Rho-related proteins, GDID4: normal hematopoietic differentiation but subtle defect in superoxide production by macrophages derived from in vitro embryonal stem cell differentiation.

  1996cited by this paper
• Prostaglandin E2 Stimulates a Ca2+-dependent K+ Channel in Human Erythrocytes and Alters Cell Volume and Filterability*

  1996cited by this paper
• HCO3(-)-dependent conformational change in gastric parietal cell AE2, a glycoprotein naturally lacking sialic acid.

  1996cited by this paper
• Therapy with oral clotrimazole induces inhibition of the Gardos channel and reduction of erythrocyte dehydration in patients with sickle cell disease.

  1996cited by this paper
• Dehydration of transferrin receptor-positive sickle reticulocytes during continuous or cyclic deoxygenation: role of KCl cotransport and extracellular calcium

  1996cited by this paper
• Clotrimazole inhibits cell proliferation in vitro and in vivo

  1995cited by this paper
• Cation transport in mouse erythrocytes: role of K(+)-Cl- cotransport in regulatory volume decrease.

  1995cited by this paper
• Ca2+-activated K+ channels of human and rabbit erythrocytes display distinctive patterns of inhibition by venom peptide toxins

  1995cited by this paper
• Control of cell volume in oocytes and eggs from Xenopus laevis.

  1995cited by this paper
• Oral administration of clotrimazole and blockade of human erythrocyte Ca(++)-activated K+ channel: the imidazole ring is not required for inhibitory activity.

  1995cited by this paper
• Role of glycogen synthase kinase 3 beta as a negative regulator of dorsoventral axis formation in Xenopus embryos.

  1995cited by this paper
• Induction of endogenous channels by high levels of heterologous membrane proteins in Xenopus oocytes.

  1995cited by this paper
• A new therapeutic approach for sickle cell disease. Blockade of the red cell Ca(2+)-activated K+ channel by clotrimazole.

  1995cited by this paper
• Function and characteristics of repetitive calcium waves associated with meiosis.

  1995cited by this paper
• A New Therapeutic Approach for Sickle Cell Disease

  1995cited by this paper
• Hypotonicity activates a native chloride current in Xenopus oocytes

  1994cited by this paper
• Mutations in the K+ channel signature sequence.

  1994cited by this paper
• Intimations of K+ channel structure from a complete functional map of the molecular surface of charybdotoxin.

  1994cited by this paper
• Relation between intracellular Ca2+ signals and Ca(2+)-activated Cl- current in Xenopus oocytes.

  1994cited by this paper
• Treatment with oral clotrimazole blocks Ca(2+)-activated K+ transport and reverses erythrocyte dehydration in transgenic SAD mice. A model for therapy of sickle cell disease.

  1994cited by this paper
• Ca(2+)-activated K+ transport in erythrocytes. Comparison of binding and transport inhibition by scorpion toxins.

  1993cited by this paper
• mSlo, a complex mouse gene encoding "maxi" calcium-activated potassium channels.

  1993cited by this paper
• Inhibition of Ca(2+)-dependent K+ transport and cell dehydration in sickle erythrocytes by clotrimazole and other imidazole derivatives.

  1993cited by this paper
• Hematopoietic commitment during embryonic stem cell differentiation in culture.

  1993cited by this paper
• Enhanced C2 Yields from Methane Oxidative Coupling by Means of a Separative Chemical Reactor

  1993cited by this paper
• Heterologous expression of specific K+ channels in T lymphocytes: functional consequences for volume regulation.

  1993cited by this paper
• Inhibition of hematopoietic development from embryonic stem cells by antisense vav RNA.

  1993cited by this paper
• Calcium signaling in cell volume regulation.

  1992cited by this paper
• Single Ca(2+)-activated K+ channels in human erythrocytes: Ca2+ dependence of opening frequency but not of open lifetimes.

  1992cited by this paper
• Specification of subunit assembly by the hydrophilic amino-terminal domain of the Shaker potassium channel.

  1992cited by this paper
• High affinity inhibition of Ca(2+)-dependent K+ channels by cytochrome P-450 inhibitors.

  1992cited by this paper
• Spiral calcium wave propagation and annihilation in Xenopus laevis oocytes.

  1991cited by this paper
• Characterization of high affinity binding sites for charybdotoxin in human T lymphocytes. Evidence for association with the voltage-gated K+ channel.

  1991cited by this paper
• Calcium wave evoked by activation of endogenous or exogenously expressed receptors in Xenopus oocytes.

  1990cited by this paper
• Analysis of the blocking activity of charybdotoxin homologs and iodinated derivatives against Ca2+-Activated K+ channels

  1989cited by this paper
• Proliferation and maturation of human erythroid progenitors in liquid culture.

  1989cited by this paper
• Ca2+-activated K+ efflux limits complement-mediated lysis of human erythrocytes.

  1989cited by this paper
• Inhibition of the in vitro formation of dense cells and of irreversibly sickled cells by charybdotoxin, a specific inhibitor of calcium-activated potassium efflux.

  1989cited by this paper
• Three types of ion channels are present on the plasma membrane of Friend erythroleukemia cells.

  1987cited by this paper
• Delay time of hemoglobin S polymerization prevents most cells from sickling in vivo.

  1987cited by this paper
• A new generation of Ca2+ indicators with greatly improved fluorescence properties.

  1985cited by this paper
• Ca2+-activated K+ channels in human red cells. Comparison of single-channel currents with ion fluxes.

  1984cited by this paper
• Properties of the CA2+-activated K+ conductance of human red cells as revealed by the patch-clamp technique.

  1983cited by this paper
• Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches

  1981cited by this paper
• The function of calcium in the potassium permeability of human erythrocytes.

  1958cited by this paper

• Fluorescent Probes to Image the KCa3.1 Channel in Tumor Cells

  2025cites this paper
• Ion Channels of the Plasma Membrane and Endolysosomes: Roles in Osmoregulation and Volume Regulation in Immune Cells.

  2025cites this paper
• Visualization of KCa3.1 Channels in Tumor Cells by Optimized Senicapoc-Bodipy Conjugates.

  2025cites this paper
• Kcnn4/KCa3.1 inhibition blunts polycystic kidney disease progression in mouse models

  2025cites this paper
• Design and structural basis of selective 1,4-dihydropyridine inhibitors of the calcium-activated potassium channel KCa3.1

  2025cites this paper
• Phospholipid scrambling induced by an ion channel/metabolite transporter complex

  2024cites this paper
• Identification of Riluzole derivatives as novel calmodulin inhibitors with neuroprotective activity by a joint synthesis, biosensor, and computational guided strategy.

  2024cites this paper
• Can KCa3.1 channel activators serve as novel inhibitors of platelet aggregation?

  2022cites this paper
• The erythroid K-Cl cotransport inhibitor [(Dihydroindenyl)oxy]acetic acid (DIOA) blocks erythroid Ca2+-activated K+ channel KCNN4.

  2022cites this paper
• Comparison of K+ Channel Families.

  2021cites this paper
• Dysregulated signalling pathways in innate immune cells with cystic fibrosis mutations

  2020cites this paper
• KCa3.1 in Epithelia

  2020cites this paper
• In silico and in vitro analysis of cation-activated potassium channels in human corneal endothelial cells.

  2020cites this paper
• Pharmacology of Small- and Intermediate-Conductance Calcium-Activated Potassium Channels.

  2020cites this paper
• Ion Channels in Glioma Malignancy.

  2020cites this paper
• Featuring how calcium channels and calmodulin affect glioblastoma behavior. A review article.

  2020cites this paper
• Development of a Cell-Based Assay for Identifying KCa3.1 Inhibitors Using Intestinal Epithelial Cell Lines

  2020cites this paper
• Lack of Kcnn4 improves mucociliary clearance in muco-obstructive lung disease

  2020cites this paper
• Calcium- and sodium-activated potassium channels (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

  2019cites this paper
• Conditional KCa3.1-transgene induction in murine skin produces pruritic eczematous dermatitis with severe epidermal hyperplasia and hyperkeratosis

  2019cites this paper
• Magnesium for treating sickle cell disease.

  2019cites this paper
• Activation mechanism of a human SK-calmodulin channel complex elucidated by cryo-EM structures

  2018cites this paper
• Kcnn4 is a modifier gene of intestinal cystic fibrosis preventing lethality in the Cftr-F508del mouse

  2018cites this paper
• Structure, Gating and Basic Functions of the Ca2+-activated K Channel of Intermediate Conductance

  2018cites this paper
• KCa3.1 Channel Modulators as Potential Therapeutic Compounds for Glioblastoma

  2017cites this paper
• The Role of the Cytoskeleton and Myosin-Vc in the Targeting of KCa3.1 to the Basolateral Membrane of Polarized Epithelial Cells

  2017cites this paper
• Structural Insights into the Atomistic Mechanisms of Action of Small Molecule Inhibitors Targeting the KCa3.1 Channel Pore

  2017cites this paper
• Magnesium for treating sickle cell disease.

  2017cites this paper
• International Union of Basic and Clinical Pharmacology. C. Nomenclature and Properties of Calcium-Activated and Sodium-Activated Potassium Channels

  2017influential citation
• Future Perspectives for the Treatment of Sickle Cell Anemia

  2016cites this paper
• Identification of KCa3.1 Channel as a Novel Regulator of Oxidative Phosphorylation in a Subset of Pancreatic Carcinoma Cell Lines

  2016cites this paper
• Novel Gardos channel mutations linked to dehydrated hereditary stomatocytosis (xerocytosis)

  2015cites this paper
• Genetic deficit of KCa3.1 channels protects against pulmonary circulatory collapse induced by TRPV4 channel activation

  2015cites this paper
• A Novel Pan-Negative-Gating Modulator of KCa2/3 Channels, Fluoro-Di-Benzoate, RA-2, Inhibits Endothelium-Derived Hyperpolarization–Type Relaxation in Coronary Artery and Produces Bradycardia In Vivo

  2015cites this paper
• KCa3.1: a new player in progressive kidney disease

  2015cites this paper
• Modulation of KCa3.1 Channels by Eicosanoids, Omega-3 Fatty Acids, and Molecular Determinants

  2014cites this paper
• PKA Reduces the Rat and Human KCa3.1 Current, CaM Binding and Ca2+ Signaling, which Requires Ser332/334 in the CaM-Binding C Terminus

  2014cites this paper
• T-type channels buddy up

  2014cites this paper
• The stimulating effects of nitric oxide on intermediate conductance Ca²⁺-activated K⁺ channels in human dermal fibroblasts through PKG pathways but not the PKA pathways.

  2014cites this paper
• Dynamic morphology and cytoskeletal protein changes during spontaneous inside-out vesiculation of red blood cell membranes

  2014cites this paper
• The Slow Afterhyperpolarization: A Target of β1-Adrenergic Signaling in Hippocampus-Dependent Memory Retrieval

  2013cites this paper
• Multiple clinical forms of dehydrated hereditary stomatocytosis arise from mutations in PIEZO1.

  2013cites this paper
• RED CELLS , IRON , AND ERYTHROPOIESIS Multiple clinical forms of dehydrated hereditary stomatocytosis arise from mutations in PIEZO 1

  2013cites this paper
• N-ethylmaleimide activates a Cl(-)-independent component of K(+) flux in mouse erythrocytes.

  2013cites this paper
• Novel Phenolic Inhibitors of Small/Intermediate-Conductance Ca2+-Activated K+ Channels, KCa3.1 and KCa2.3

  2013cites this paper
• Strain-specific variations in cation content and transport in mouse erythrocytes.

  2013cites this paper
• Exposure to sparsely and densely ionizing irradiationresults in an immediate activation of K+channels in A549 cells and in human peripheral bloodlymphocytes.

  2013cites this paper
• red blood cells Distribution of plasma membrane Ca2+ pump activity in normal human

  2013cites this paper
• Endothelial Small-Conductance and Intermediate-Conductance KCa Channels: An Update on Their Pharmacology and Usefulness as Cardiovascular Targets

  2013cites this paper
• activation in normal and sickle red blood cells Distribution of dehydration rates generated by maximal Gardos-channel

  2013cites this paper
• invasion by Plasmodium falciparum The hydration state of human red blood cells and their susceptibility to

  2013cites this paper
• Development of a QPatch Automated Electrophysiology Assay for Identifying KCa3.1 Inhibitors and Activators

  2013cites this paper
• Hypotonic Regulation of Mouse Epithelial Sodium Channel in Xenopus laevis Oocytes

  2013cites this paper
• Molecular basis of potassium channels in pancreatic duct epithelial cells

  2013cites this paper
• KCa2 and KCa3 Channels in Learning and Memory Processes, and Neurodegeneration

  2012cites this paper
• Trafficking of Intermediate (KCa3.1) and Small (KCa2.x) Conductance, Ca2+‐Activated K+ Channels: a Novel Target for Medicinal Chemistry Efforts?

  2012cites this paper
• Regulation of ion channels by membrane lipids.

  2012cites this paper
• Therapeutic potential of KCa 3 . 1 blockers : an overview of recent advances , and promising trends

  2012cites this paper
• Transcriptome profiling of LH-producing gonadotropes in female medaka - with special emphasis on calcium-activated potassium channels

  2012cites this paper
• Cyclic AMP-induced K+ secretion occurs independently of Cl- secretion in rat distal colon.

  2012cites this paper
• Trpc2 depletion protects red blood cells from oxidative stress-induced hemolysis.

  2012cites this paper
• Genetic KCa3.1-Deficiency Produces Locomotor Hyperactivity and Alterations in Cerebral Monoamine Levels

  2012cites this paper
• X-ray microanalysis investigation of the changes in Na, K, and hemoglobin concentration in plasmodium falciparum-infected red blood cells.

  2011cites this paper
• IKCa agonist (NS309)-elicited all-or-none dehydration response of human red blood cells is cell-age dependent.

  2011cites this paper
• Characteristics of Kcnn4 channels in the apical membranes of an intestinal epithelial cell line.

  2011cites this paper
• Ion channels in human red blood cell membrane: actors or relics?

  2011cites this paper
• Characteristics of Kcnn 4 channels in the apical membranes of an intestinal epithelial cell line

  2011cites this paper
• Hydrogen ion dynamics in human red blood cells

  2010cites this paper
• Effects of elevated intracellular calcium on the osmotic fragility of human red blood cells.

  2010cites this paper
• Cholesterol and ion channels.

  2010cites this paper
• Immunofluorescence-based assay to identify modulators of the number of plasma membrane KCa3.1 channels.

  2010cites this paper
• Local Membrane Deformations Activate Ca2+-Dependent K+ and Anionic Currents in Intact Human Red Blood Cells

  2010cites this paper
• Mucosal potassium efflux mediated via Kcnn4 channels provides the driving force for electrogenic anion secretion in colon.

  2010cites this paper
• Cloning and identification of tissue-specific expression of KCNN4 splice variants in rat colon.

  2010cites this paper
• Sarcoplasmic reticulum function in smooth muscle.

  2010cites this paper
• Ca2+-activated K+ channels: from protein complexes to function.

  2010cites this paper
• Therapeutic potential of KCa3.1 blockers: recent advances and promising trends

  2010cites this paper
• Dynamical behavior of the human red blood cell ionic channels

  2009cites this paper
• Estradiol rapidly induces the translocation and activation of the intermediate conductance calcium activated potassium channel in human eccrine sweat gland cells.

  2009cites this paper
• Pharmacotherapy in sickle cell disease – state of the art and future prospects

  2009cites this paper
• Disorders of hemoglobin: Genetics, pathophysiology, and clinical management, second edition

  2009cites this paper
• ECOLE DOCTORALE VIE-AGRO-SANTE présentée par Dynamical behaviour of the human red blood cell ionic channels

  2009cites this paper
• Preserved function of the plasma membrane calcium pump of red blood cells from diabetic subjects with high levels of glycated haemoglobin.

  2009cites this paper
• Mechanistic details of BK channel inhibition by the intermediate conductance, Ca2+-activated K channel

  2009cites this paper
• THE IMPACT OF ULCERATION ON MOTILITY REFLEX CIRCUITS IN GUINEA PIG TNBS COLITIS

  2009cites this paper
• Molecular physiology and genetics of Na+-independent SLC4 anion exchangers

  2009cites this paper
• The role of cell cholesterol and the cytoskeleton in the interaction between IK1 and maxi-K channels.

  2009cites this paper
• IK1 channel activity contributes to cisplatin sensitivity of human epidermoid cancer cells.

  2008cites this paper
• Apparent intermediate K conductance channel hyposmotic activation in human lens epithelial cells.

  2008cites this paper
• IK-Ca Intermediate Conductance Calcium Activated Potassium Channel

  2008cites this paper
• Modeling of the Inhibition of the Intermediate-Conductance Ca2+-Activated K+ Channel (IKCa1) by Some Triarylmethanes Using Quantum Chemical Properties Derived From Ab Initio Calculations

  2008cites this paper
• Physiology and pathophysiology of potassium channels in gastrointestinal epithelia.

  2008cites this paper
• Reduced DIDS-sensitive chloride conductance in Ae1-/- mouse erythrocytes.

  2008cites this paper
• Let's look at cysts from both sides now.

  2008cites this paper
• Modulators of small- and intermediate-conductance calcium-activated potassium channels and their therapeutic indications.

  2007cites this paper
• Phase I study of magnesium pidolate in combination with hydroxycarbamide for children with sickle cell anaemia

  2007cites this paper
• An NH2-Terminal Multi-Basic RKR Motif Is Required for the ATP-Dependent Regulation of hIK1

  2007cites this paper
• Age Decline in the Activity of the Ca2+-sensitive K+ Channel of Human Red Blood Cells

  2007cites this paper
• Characterisation of three pathways for osmolyte efflux in human erythroleukemia cells.

  2007cites this paper
• A C-terminal Domain in KCC2 Confers Constitutive K+-Cl- Cotransport*

  2006cites this paper