Affinage

KCNN4

Intermediate conductance calcium-activated potassium channel protein 4 · UniProt O15554

Length
427 aa
Mass
47.7 kDa
Annotated
2026-06-10
100 papers in source corpus 39 papers cited in narrative 39 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KCNN4 (KCa3.1/hSK4/hKCa4) is an intermediate-conductance, voltage-independent, inwardly rectifying Ca2+-activated K+ channel that drives K+ efflux to hyperpolarize the membrane and thereby amplify Ca2+ influx in nonexcitable cells, coupling cellular Ca2+ signaling to immune activation, cell volume control, and migration (PMID:9407042, PMID:12773623, PMID:20080610). The channel has no intrinsic Ca2+-binding sites; instead it is constitutively associated with calmodulin at a C-terminal CaM-binding domain, and Ca2+-loaded CaM N-lobe binding gates the channel through defined residues that set open probability and deactivation kinetics (PMID:10329683, PMID:23797421). Channel activity is set by a distinctive C-terminal regulatory hub: NDPK-B directly phosphorylates histidine 358 to activate the channel by relieving copper-mediated inhibition, while protein histidine phosphatase PHPT-1 dephosphorylates H358 to inhibit it, and PKA phosphorylation of Ser334 reduces CaM binding and open probability (PMID:17157250, PMID:18796614, PMID:27542194, PMID:25274816). Additional inputs converge on the C terminus, including direct AMPK-γ1 binding that inhibits the channel and a 14-amino-acid motif conferring PI(3)P-dependent activation (PMID:16251351, PMID:19052260). At the plasma membrane the channel is functionally coupled to Orai1/CRAC channels that supply its activating Ca2+ and is scaffolded by junctophilins into Cav1.3–RyR2 complexes to generate the neuronal slow afterhyperpolarization current (PMID:31461656, PMID:26177720); surface levels are controlled by clathrin/Rab5 endocytosis and Rab7/ESCRT-dependent lysosomal degradation (PMID:20720181, PMID:24158513). Through this Ca2+-amplifying role KCa3.1 governs CD4 T-cell activation and cytokine production, microglial neuroinflammation via p38 MAPK, osteoclast/multinucleate-giant-cell formation via CaMKIV/NFATc1, and NLRP3 inflammasome activation downstream of PIEZO1-mediated Ca2+ entry (PMID:17202491, PMID:20080610, PMID:38134241, PMID:29246953). In erythrocytes KCa3.1 is the Gardos channel that mediates K+ efflux for volume homeostasis, and gain-of-function KCNN4 mutations are associated with hereditary xerocytosis (PMID:12773623, PMID:26198474).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1997 High

    Established the molecular identity of an intermediate-conductance, voltage-independent Ca2+-activated K+ channel with very high Ca2+ sensitivity, defining a distinct channel class enriched in nonexcitable tissues.

    Evidence Heterologous expression in CHO/HEK293 cells with patch-clamp and pharmacological profiling

    PMID:9380751 PMID:9407042

    Open questions at the time
    • Did not define the Ca2+-sensing mechanism
    • No structural basis for gating
  2. 1999 High

    Resolved how a channel lacking intrinsic Ca2+ sites senses Ca2+ — a constitutively bound calmodulin at the proximal C terminus confers Ca2+ gating and links the channel to T-cell proliferation and volume regulation.

    Evidence Deletion mutagenesis mapping of the CaM-binding domain with patch-clamp and functional assays

    PMID:10329683

    Open questions at the time
    • Did not define which CaM residues drive gating
    • Distal C-terminal requirement unexplained
  3. 2013 High

    Defined the structural determinants of CaM-dependent gating, identifying specific CaM-binding-domain residues controlling open probability versus complex stability/deactivation.

    Evidence Structure-guided cross-linking mutagenesis with patch-clamp of mutant channels

    PMID:23797421

    Open questions at the time
    • Based on homology modeling, not a KCa3.1 structure
    • Single lab
  4. 2005 High

    Identified a 14-aa C-terminal motif conferring PI(3)P-dependent activation, implying recruitment of an accessory regulatory subunit required for Ca2+ gating.

    Evidence Chimeric KCa3.1/KCa2.3 channels and site-directed mutagenesis with patch-clamp

    PMID:16251351

    Open questions at the time
    • Proposed accessory subunit not identified
    • Indirect regulation mechanism unresolved
  5. 2006 High

    Discovered histidine-358 phosphorylation as a unique activating regulatory mechanism, with NDPK-B directly binding and phosphorylating the C terminus to enable channel-driven Ca2+ influx and T-cell activation.

    Evidence Co-IP, in vitro kinase assay, H358 mutagenesis, T-cell patch-clamp and siRNA

    PMID:17157250

    Open questions at the time
    • Did not identify the opposing phosphatase
    • Molecular consequence of H358 phosphorylation on gating unclear
  6. 2008 High

    Completed the histidine phospho-switch by identifying PHPT-1 as the phosphatase that dephosphorylates H358 to inhibit the channel, establishing reciprocal kinase/phosphatase control.

    Evidence Co-IP, phosphatase-dead mutant, siRNA, patch-clamp and Ca2+ imaging

    PMID:18796614

    Open questions at the time
    • Did not explain why H358 phosphorylation gates the channel
  7. 2016 High

    Provided the mechanistic basis of the H358 switch — phosphorylation activates the channel by antagonizing copper-mediated inhibition, linking intracellular copper status to T-cell Ca2+ signaling.

    Evidence In vitro copper inhibition assays, H358 mutagenesis, patch-clamp and Ca2+ flux in copper-deficient T cells

    PMID:27542194

    Open questions at the time
    • Copper-binding site on the channel not defined
    • Physiological source of inhibitory copper unclear
  8. 2008 High

    Identified additional C-terminal regulatory inputs: direct AMPK-γ1 binding inhibits the channel, coupling metabolic state to K+ conductance in epithelia.

    Evidence Two-hybrid, pull-down, endogenous co-IP, inside-out patch-clamp and Ussing chamber currents

    PMID:19052260

    Open questions at the time
    • Whether AMPK phosphorylates the channel directly not resolved
    • Single lab
  9. 2014 High

    Defined PKA inhibitory regulation through Ser334 phosphorylation that reduces CaM binding and open probability, linking GPCR/cAMP signaling to channel downregulation.

    Evidence S334A mutagenesis, CaM-affinity chromatography, single-channel patch-clamp, Ca2+ imaging in microglia

    PMID:25274816

    Open questions at the time
    • Integration of PKA, NDPK-B/PHPT-1, and AMPK inputs not reconciled
  10. 2004 High

    Demonstrated in vivo physiological roles via clean genetic deletion: Kcnn4 loss abolishes IK in red cells and T lymphocytes and impairs their volume regulation, while sparing salivary secretion, establishing cell-type-specific requirement.

    Evidence Kcnn4 knockout mouse with patch-clamp, K+ permeability, and fluid secretion assays

    PMID:15347667

    Open questions at the time
    • Did not address inflammatory or migratory roles
    • Compensation in unaffected tissues not explained
  11. 2003 High

    Identified KCa3.1 as the long-sought erythrocyte Gardos channel, providing molecular identity to a classic red-cell K+ pathway.

    Evidence RT-PCR, Northern/Western of RBC ghosts, inside-out patch-clamp, heterologous recapitulation of native channel behavior

    PMID:12773623

    Open questions at the time
    • Did not address disease mutations affecting Gardos function
  12. 2015 Low

    Linked KCNN4 to human disease, associating conserved-residue mutations with hereditary xerocytosis via a predicted gain-of-function (delayed inactivation) causing erythrocyte dehydration.

    Evidence Whole-exome sequencing, segregation in two kindreds, mutation-effect prediction

    PMID:26198474

    Open questions at the time
    • No direct functional channel assay performed in this study
    • Gating defect inferred computationally only
  13. 2010 High

    Established the immunological function of the channel in adaptive immunity: KCa3.1 supports TCR-driven Ca2+ influx and cytokine output selectively in Th1/Th2 cells and is required for T-cell-mediated colitis.

    Evidence Knockout CD4 T cells, Ca2+ flux/cytokine assays, two in vivo colitis models

    PMID:20080610

    Open questions at the time
    • Mechanism of subset selectivity (Th1/2 vs Treg/Th17) not defined
  14. 2013 Medium

    Showed plasma-membrane KCa3.1 is functionally coupled to Orai1/CRAC channels that supply the Ca2+ for channel activation, integrating store-operated entry with K+ efflux to sustain Ca2+ signaling and migration.

    Evidence Co-IP, co-localization, Orai1 E106Q dominant negative, patch-clamp in mast cells and microglia

    PMID:23620825 PMID:26177720

    Open questions at the time
    • Whether the KCa3.1–Orai1 association is direct vs scaffolded not resolved
    • Stoichiometry of the functional coupling unknown
  15. 2013 Medium

    Defined surface-level control of the channel through clathrin/Rab5 endocytosis and Rab7/ESCRT-dependent lysosomal degradation, a pathway exploited by Gb3 to suppress endothelial KCa3.1 and impair vasorelaxation.

    Evidence siRNA/dominant-negative of clathrin, Rab5, Rab7, TSG101/CHMP4/VPS4, co-IP, imaging, EM, vessel relaxation assay

    PMID:20720181 PMID:24158513

    Open questions at the time
    • Trafficking signals on KCa3.1 directing endocytosis not mapped
    • Regulation of degradation rate by upstream signals unclear
  16. 2019 High

    Revealed neuronal scaffolding: junctophilins JPH3/4 tether a Cav1.3–RyR2–KCa3.1 tripartite complex at ER–PM junctions in hippocampal neurons, and densin/CaMKII-prolonged Cav1.3 Ca2+ influx drives KCa3.1 to generate the slow afterhyperpolarization.

    Evidence dSTORM/FRET, shRNA, intracellular antibody infusion, heterologous coexpression, whole-cell patch-clamp

    PMID:29038242 PMID:31461656

    Open questions at the time
    • Direct KCa3.1–junctophilin contact not biochemically mapped
    • Generality across neuron types untested
  17. 2014 High

    Established KCa3.1 as a regulator of myeloid cell fusion and bone biology, where it controls Ca2+-dependent CaMKIV/CREB/c-fos/NFATc1 signaling driving osteoclast and multinucleate-giant-cell formation.

    Evidence Systems genetics, Kcnn4 knockout mouse, osteoclast/MGC and arthritis models, Ca2+ imaging, signaling Western blots

    PMID:25131209 PMID:29246953

    Open questions at the time
    • How channel activity is gated specifically during fusion not defined
  18. 2007 Medium

    Implicated the channel in CNS innate immunity, showing microglial KCa3.1 drives activation, iNOS/NO/peroxynitrite production, and p38 MAPK-dependent neurotoxicity, with KCa3.1 expression itself shaped by IL-4 (JAK3/Ras/MEK/ERK/AP-1) and PKG/ROS/CaMKII inputs.

    Evidence TRAM-34 blockade, co-culture, NO/peroxynitrite assays, in vivo optic nerve injury, kinase-inhibitor panels, perforated/inside-out patch-clamp

    PMID:17202491 PMID:25071444 PMID:25904916

    Open questions at the time
    • Direct molecular link between K+ efflux and p38 activation unresolved
    • PKG/ROS effect is indirect with no defined channel-proximal effector
  19. 2023 High

    Placed KCa3.1 within mechanotransductive innate immune signaling, where PIEZO1-triggered Ca2+ influx activates the channel and the resulting K+ efflux drives NLRP3 inflammasome activation in gout and CAPS models.

    Evidence Myeloid Piezo1/2 KO, Yoda1, KCNN4 inhibition, inflammasome and Ca2+ assays, in vivo arthritis models

    PMID:35799057 PMID:38134241

    Open questions at the time
    • Whether K+ efflux directly senses or merely permits NLRP3 assembly not dissected
    • Coupling of PIEZO1 Ca2+ entry to channel activation not biochemically mapped
  20. 2022 Medium

    Identified a non-canonical mitochondrial pool (mitoKCa3.1) in the inner membrane of cancer cells whose inhibition triggers ROS, depolarization, and death, expanding the channel's role beyond the plasma membrane.

    Evidence Mitochondria-targeted vs impermeant blockers, membrane-potential/ROS assays, NF-κB/BNIP-3/CDC-42 manipulation, orthotopic models

    PMID:36539400

    Open questions at the time
    • How the channel is imported/inserted into the inner mitochondrial membrane unknown
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple convergent C-terminal regulatory inputs (H358 phospho-switch/copper, Ser334/PKA, AMPK-γ1, PI(3)P, CaM) are integrated in real time on a single channel, and the structural basis of gating, remain unresolved.
  • No experimental KCa3.1 structure in the corpus
  • Crosstalk and hierarchy among regulatory inputs undefined
  • Mechanism of mitochondrial targeting unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 3
Localization
GO:0005886 plasma membrane 4 GO:0005764 lysosome 2 GO:0005739 mitochondrion 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3 R-HSA-9609507 Protein localization 2
Partners
CALM1GABRPJPH3JPH4NME2ORAI1PHPT1PRKAA1/PRKAG1
Complex memberships
Cav1.3-RyR2-KCa3.1 junctophilin-tethered complexKCa3.1-calmodulin complex

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 hSK4 (KCNN4) encodes a calcium-activated potassium channel with ~12 pS conductance in physiological saline, very high Ca2+ affinity (EC50 ~95 nM), and contains a leucine zipper-like domain in its C terminus. It is predominantly expressed in nonexcitable tissues. Heterologous expression in CHO cells, patch-clamp electrophysiology Proceedings of the National Academy of Sciences of the United States of America High 9380751
1997 hKCa4 (KCNN4) encodes an intermediate conductance (~33 pS in symmetrical K+), voltage-independent, inwardly rectifying Ca2+-activated K+ channel in human T lymphocytes, activated by intracellular Ca2+ (Kd ~270 nM) with ~3 Ca2+ ions per channel cooperativity; blocked by charybdotoxin and clotrimazole but resistant to apamin, iberiotoxin, and margatoxin. Heterologous expression in HEK293 cells, patch-clamp electrophysiology, pharmacological profiling The Journal of biological chemistry High 9407042
1999 hSK4 (KCNN4) lacks intrinsic Ca2+-binding sites but contains a Ca2+-dependent calmodulin (CaM)-binding site mapped to the proximal C terminus (Ct1). Deletion of either Ct1 or the distal C terminus abolishes channel function. The channel regulates membrane potential, T cell proliferation, and volume regulation. CaM-binding domain mapping by deletion mutagenesis, stable CHO cell expression, patch-clamp, proliferation and volume assays The Journal of biological chemistry High 10329683
2006 NDPK-B (nucleoside diphosphate kinase B), a mammalian histidine kinase, directly binds KCa3.1 and activates it by phosphorylating histidine 358 in the carboxyl terminus. This histidine phosphorylation is required for KCa3.1 channel activity and subsequent Ca2+ influx and CD4 T cell activation. NDPK-B functions downstream of PI(3)P. Co-immunoprecipitation, in vitro kinase assay, site-directed mutagenesis (H358), patch-clamp in T cells, siRNA knockdown Molecular cell High 17157250
2008 Protein histidine phosphatase 1 (PHPT-1) directly binds KCa3.1 and inhibits it by dephosphorylating histidine 358. Overexpression of wild-type but not phosphatase-dead PHPT-1 inhibited channel activity; siRNA knockdown of PHPT-1 increased KCa3.1 activity, Ca2+ influx, and T cell proliferation. Co-immunoprecipitation, phosphatase-dead mutant overexpression, siRNA knockdown, patch-clamp, Ca2+ imaging Proceedings of the National Academy of Sciences of the United States of America High 18796614
2005 Phosphatidylinositol 3-phosphate [PI(3)P] indirectly activates KCa3.1 via a stretch of 14 amino acids in the carboxy-terminal calmodulin binding domain. This 14-aa segment is sufficient to confer PI(3)P regulation when transferred to the related KCa2.3 channel, suggesting it recruits an accessory regulatory subunit required for Ca2+ gating. Chimeric channel construction between KCa3.1 and KCa2.3, patch-clamp, site-directed mutagenesis Molecular biology of the cell High 16251351
2016 Histidine 358 phosphorylation activates KCa3.1 by antagonizing copper-mediated inhibition of the channel. CD4+ T cells deficient in intracellular copper show increased KCa3.1 histidine phosphorylation and channel activity, leading to increased Ca2+ flux and cytokine production. In vitro copper inhibition assays, H358 mutagenesis, patch-clamp, Ca2+ flux measurements in copper-deficient T cells eLife High 27542194
2003 The KCNN4 (hSK4) isoform encodes the Gardos channel in human red blood cells. Only SK4 mRNA was detected in reticulocytes; SK4 protein was found in red blood cell ghost membranes; heterologously expressed SK4 recapitulates the Ko+-dependence behavior of the native Gardos channel, and temperature-dependent reduction of open probability is shared by native RBC and SK4-expressing CHO cells. RT-PCR, Northern blot, Western blot of RBC ghosts, inside-out patch-clamp, heterologous expression in CHO cells Proceedings of the National Academy of Sciences of the United States of America High 12773623
2004 Genetic deletion of Kcnn4 in mice abolishes IK channel activity in red blood cells and T lymphocytes, severely impairing volume regulation in both cell types. Despite loss of IK in parotid acinar cells, fluid secretion and regulatory volume decrease remain normal, indicating Kcnn4 is dispensable for salivary gland secretion. Kcnn4 knockout mouse, patch-clamp, K+ permeability assays, fluid secretion measurements The Journal of biological chemistry High 15347667
2008 AMP-activated protein kinase (AMPK) inhibits KCa3.1 channel activity. The AMPK γ1-subunit directly interacts with a C-terminal region (Asp380–Ala400) of KCa3.1 as shown by two-hybrid screening and pull-down. Co-immunoprecipitation confirmed the KCa3.1/AMPK-γ1 complex at endogenous levels. AMPK activation with AICAR decreased KCa3.1-mediated short-circuit currents in bronchial epithelial cells. Two-hybrid screening, pull-down assay, co-immunoprecipitation in bronchial cells, inside-out patch-clamp, Ussing chamber short-circuit current American journal of physiology. Cell physiology High 19052260
2013 CaM N-lobe binding to KCa3.1 controls gating: residues R362 and E363 (electrostatic) and M368 (hydrophobic) in the CaM-binding domain are key determinants of channel activation and open probability at saturating Ca2+, while S367 solvation energy controls the stability of the CaM–KCa3.1 complex and deactivation kinetics. Structural homology modeling based on rSK2 crystal structure, cross-linking mutagenesis (R362-K75 CaM), patch-clamp of mutant channels The Journal of general physiology High 23797421
2014 PKA phosphorylates Ser334 in the CaM-binding C terminus of KCa3.1, reducing CaM binding and channel open probability. Mutating S334A abolishes PKA-dependent regulation. PKA activation through the adenosine A2a receptor similarly reduces KCa3.1 current and subsequent CRAC-mediated Ca2+ entry in microglia. Site-directed mutagenesis (S334A), CaM-affinity chromatography, single-channel patch-clamp, Ca2+ imaging in microglia and HEK293 cells The Journal of neuroscience : the official journal of the Society for Neuroscience High 25274816
2010 Plasma membrane KCa3.1 is internalized and targeted to lysosomes for degradation via a Rab7- and ESCRT-dependent pathway. TSG101 (ESCRT-I) co-immunoprecipitates with KCa3.1; dominant-negative TSG101, CHMP4, and VPS4 each inhibit KCa3.1 degradation rate. Immunofluorescence, electron microscopy, co-immunoprecipitation, dominant-negative constructs, siRNA knockdown of Rab7/ESCRT components American journal of physiology. Cell physiology High 20720181
2013 Globotriaosylceramide (Gb3) triggers clathrin-dependent endocytosis and lysosomal degradation of endothelial KCa3.1. Knockdown of clathrin, Rab5, or lysosomal inhibitor treatment all rescue KCa3.1 expression and current; Rab5 knockdown also restores endothelium-dependent relaxation. Pharmacological inhibitors, siRNA knockdown of clathrin and Rab5, immunofluorescence, patch-clamp, vessel relaxation assay Arteriosclerosis, thrombosis, and vascular biology Medium 24158513
2010 Three splice variants of KCNN4 (KCNN4a, KCNN4b, KCNN4c) are expressed in rat colon with tissue specificity: KCNN4a in smooth muscle, KCNN4b/c in epithelial cells. KCNN4b and KCNN4c encode basolateral and apical membrane proteins, respectively. KCNN4c, lacking the S2 transmembrane segment, requires coexpression of a large conductance K+ channel β-subunit for plasma membrane expression. RT-PCR, real-time qPCR, immunofluorescence, 86Rb efflux assay, heterologous coexpression American journal of physiology. Cell physiology Medium 20445171
2007 KCNN4/KCa3.1 is expressed in rat microglia and contributes to microglial activation, inducible nitric oxide synthase upregulation, nitric oxide and peroxynitrite production, and p38 MAPK activation (but not NF-κB), leading to neurotoxicity. TRAM-34 treatment of microglia (not neurons) reduces neuronal killing, and intraocular TRAM-34 reduces retinal ganglion cell degeneration after optic nerve transection. Selective pharmacological blockade (TRAM-34), Transwell co-culture assay, fluorescence-based NO/peroxynitrite assays, in vivo optic nerve injury model The Journal of neuroscience : the official journal of the Society for Neuroscience Medium 17202491
2008 KCa3.1 channels localize specifically to endothelial cell projections at myoendothelial gap junctions in mesenteric arteries, co-localizing with Na+/K+-ATPase α2/α3. PKA activation blocks KCa3.1 contribution to EDHF hyperpolarization independent of endothelial [Ca2+]i changes. KCa3.1-mediated hyperpolarization links to arterial relaxation primarily through Na+/K+-ATPase (K+ acting as EDHF), distinct from KCa2.3 pathways. Confocal z-stack immunofluorescence of pressurized arteries, pharmacological blockade (forskolin, TRAM-34), electrophysiology, Ca2+ imaging Circulation research Medium 18403729
2010 KCa3.1 knockout CD4 T cells show decreased TCR-stimulated Ca2+ influx and IL-2 production. KCa3.1 loss impairs Ca2+ influx and cytokine production in Th1 and Th2 cells but not in T-regulatory or Th17 cells. KCa3.1-/- mice are protected from T-cell-mediated colitis in two IBD models. KCa3.1 knockout mouse, adoptive transfer colitis model, TNBS colitis model, Ca2+ flux measurements, cytokine assays Proceedings of the National Academy of Sciences of the United States of America High 20080610
2012 KCa3.1 localizes to the uropod of migrating activated human T lymphocytes (not the leading edge), and co-localizes with TRPM7. Blockade of KCa3.1 (TRAM-34) but not Kv1.3, CRAC, or TRPM4 inhibits T cell migration on ICAM-1 surfaces; Ca2+ oscillations are detected at the uropod where KCa3.1 and TRPM7 accumulate. Confocal microscopy on ICAM-1 polymer surfaces, Ca2+ imaging, pharmacological blockade, T cell migration assays PloS one Medium 22952790
2013 KCa3.1 is selectively coupled to P2Y2 receptor (UTP) activation in rat microglia. KCa3.1 current is activated by Ca2+ entry through CRAC/Orai1 channels; both channels facilitate Ca2+ store refilling and are physically associated. Blocking either KCa3.1 or CRAC/Orai1 inhibits microglial migration stimulated by UTP. Whole-cell patch-clamp, Ca2+ imaging, pharmacological blockade, co-immunoprecipitation (implied close association), migration assay PloS one Medium 23620825
2013 Bradykinin raises [Ca2+]i in glioma cells, which activates KCa3.1 channels and Ca2+-dependent Cl- channels (ClC-3, activated via CaMKII) in a coordinated manner to drive a biphasic voltage response that mediates chemotactic migration. Inhibition of either KCa3.1 or ClC-3 abolishes bradykinin-induced chemotaxis and reduces tumor expansion in brain slices. Simultaneous fura-2 Ca2+ imaging and perforated patch-clamp, pharmacological blockade (TRAM-34, DIDS), CaMKII inhibition, shRNA knockdown of ClC-3, brain slice migration assay The Journal of neuroscience : the official journal of the Society for Neuroscience High 23345219
2014 Kcnn4 is required for osteoclast and multinucleate giant cell (MGC) formation in rodents and humans. Genetic deletion of Kcnn4 reduces macrophage multinucleation through modulation of Ca2+ signaling, increases bone mass, and improves clinical outcome in arthritis models. Kcnn4 was identified as the most significantly trans-regulated gene in a macrophage multinucleation network. Systems genetics in rat macrophages, Kcnn4 knockout mouse (osteoclast/MGC formation, bone mass, arthritis model), Ca2+ signaling assays Cell reports High 25131209
2013 KCNN4 channels mediate EMT induced by PRL-3 in colorectal cancer by increasing intracellular Ca2+, activating CaM-kinase II and GSK-3β, increasing Snail expression, and downregulating E-cadherin. KCNN4 siRNA or TRAM-34 restores E-cadherin and inhibits Snail. siRNA knockdown, pharmacological blockade (TRAM-34), intracellular Ca2+ measurements, Western blot for CaMKII, GSK-3β, Snail, E-cadherin Medical oncology Medium 23572150
2019 GABRP physically interacts with KCNN4 (co-immunoprecipitation, proximity ligation assay) to induce Ca2+ entry, which activates NF-κB signaling and induces CXCL5 and CCL20 expression in pancreatic cancer cells, facilitating macrophage infiltration in a GABA-independent manner. Co-immunoprecipitation, proximity ligation assay, electrophysiology, NF-κB reporter assay, transwell and orthotopic xenograft models Gut Medium 30826748
2019 Junctophilin proteins (JPH3 and JPH4) tether a Cav1.3–RyR2–KCa3.1 tripartite complex at the plasma membrane–ER junction in CA1 hippocampal neurons. shRNA knockdown of JPH3/4 dissociates the complex and reduces the slow afterhyperpolarization current (IsAHP). Infusing JPH3/4 antibodies intracellularly also reduces IsAHP and spike accommodation, confirming functional coupling. dSTORM super-resolution microscopy, FRET imaging, shRNA knockdown, intracellular antibody infusion, whole-cell patch-clamp Cell reports High 31461656
2017 CaV1.3 channels exhibit long-duration calcium-dependent facilitation (L-CDF, up to 8 s) when coexpressed with densin and CaMKII, and this prolonged Ca2+ influx strongly activates KCa3.1 to generate a slow afterhyperpolarization tail current in CA1 pyramidal cells. CaV1.3 L-CDF and KCa3.1 coupling is reduced by CaMKII blockade and densin siRNA knockdown. Heterologous coexpression (tsA-201 cells), whole-cell patch-clamp, CaMKII inhibitor, siRNA knockdown of densin, pharmacological block of CaV1 (isradipine) The Journal of neuroscience : the official journal of the Society for Neuroscience Medium 29038242
2013 KCa3.1 is expressed in neuroblasts of the SVZ and RMS but absent in olfactory bulb neurons. Pharmacological inhibition of KCa3.1 prolongs the stationary phase of saltatory neuroblast migration, reducing migration speed by >50%. TRAM-34 injection in vivo significantly reduced the number of neuroblasts reaching the olfactory bulb. KCa3.1 activity depends on Ca2+ influx through TRPC channels (likely TRPC1). Patch-clamp of neuroblasts in situ, time-lapse confocal microscopy, pharmacological inhibition (TRAM-34, clotrimazole), in vivo injection of TRAM-34, immunolabeling Cerebral cortex Medium 23585521
2019 PKA-mediated downregulation of KCa3.1 channels reduces the slow afterhyperpolarization (KCa-sAHP component) in epileptic hippocampal neurons, contributing to hyperexcitability. Acute application of PKA inhibitors reverses KCa3.1 downregulation and normalizes neuronal spike output. Whole-cell patch-clamp of rat CA1 neurons, PKA inhibitors, pilocarpine epilepsy model The Journal of neuroscience : the official journal of the Society for Neuroscience Medium 31672789
2023 PIEZO1 activation triggers Ca2+ influx that activates KCNN4 (KCa3.1), leading to K+ efflux and NLRP3 inflammasome activation. Myeloid-specific deletion of PIEZO1/2 protects mice from gouty arthritis. Pharmacological inhibition of KCNN4 alleviates autoinflammation in CAPS patient cells and CAPS-mutation mice. Genetic deletion (myeloid-specific Piezo1/2 KO), pharmacological PIEZO1 agonist (Yoda1), KCNN4 inhibition, inflammasome activation assays, Ca2+ flux measurements, in vivo arthritis model Science immunology High 38134241
2022 DSS potentiates NLRP3 inflammasome activation in macrophages by augmenting KCa3.1-mediated K+ efflux. Pharmacological blockade (TRAM-34) or genetic deletion of Kcnn4 attenuates NLRP3 inflammasome assembly in vivo and ameliorates DSS-induced colitis severity. Kcnn4 knockout mouse, TRAM-34 pharmacological blockade, inflammasome assembly assays, in vitro macrophage stimulation, DSS colitis model Cellular & molecular immunology Medium 35799057
2015 Mutations in KCNN4 (Gardos channel) at a highly conserved residue are associated with hereditary xerocytosis. Both identified mutations are predicted to cause delayed channel inactivation, consistent with a gain-of-function mechanism causing erythrocyte dehydration. Whole-exome sequencing, segregation analysis in two HX kindreds, mutation effect prediction algorithms Blood Low 26198474
2014 IL-4 upregulates KCNN4 mRNA and KCa3.1 current in alternative-activated rat microglia via the type I IL-4 receptor, requiring JAK3, Ras/MEK/ERK signaling, and the AP-1 transcription factor (not JAK2, STAT6, or PI3K). The increased KCa3.1 is required for IL-4-enhanced microglial migration. Real-time PCR, patch-clamp, protein synthesis inhibition, kinase inhibitor panel, migration assay (TRAM-34 blockade) Frontiers in cellular neuroscience Medium 25071444
2015 PKG elevates KCa3.1 current in microglia through a ROS-dependent, CaMKII-mediated pathway; H2O2 mimics and ROS scavengers/CaMKII inhibitors block the PKG effect. However, direct application of cGMP, PKG, or H2O2 to inside-out patches does not affect single-channel activity or Ca2+ dependence, indicating the regulation is indirect and requires intact intracellular signaling. Perforated-patch whole-cell recordings in microglia, inside-out single-channel patch-clamp in HEK293, selective PKG inhibitor (KT5823), ROS scavenger, CaMKII inhibitor, H2O2 Frontiers in immunology Medium 25904916
2015 Orai1 co-immunoprecipitates with KCa3.1 (but not Orai2) when coexpressed in HEK293 cells, and both channels co-localize at the plasma membrane. In human lung mast cells, KCa3.1 activation is highly dependent on Ca2+ influx through Orai1; Orai1 E106Q dominant-negative mutant ablates KCa3.1 currents. Co-immunoprecipitation, confocal co-localization, dominant-negative Orai1 E106Q mutant, patch-clamp Cell communication and signaling Medium 26177720
2015 KCa3.1 co-immunoprecipitates and co-distributes with β1-integrin in alveolar epithelial cells on fibronectin matrix. KCa3.1 inhibition/silencing impairs fibronectin-stimulated wound healing, cell migration, and proliferation. KCa3.1 and TRPC4 have additive inhibitory effects on alveolar repair. Co-immunoprecipitation, immunofluorescence co-localization, siRNA knockdown, wound-healing assays, KCa3.1 blocker Respiratory research Medium 26335442
2013 Adenosine selectively inhibits KCa3.1 (not Kv1.3 or TRPM7) in activated human T cells via A2A receptor and cAMP/PKAI signaling pathway. This inhibition reduces T cell motility on ICAM-1 surfaces and IL-2 secretion; the adenosine effect on migration is abolished by pre-exposure to TRAM-34, placing KCa3.1 downstream of A2A/PKAI. Patch-clamp, selective receptor agonists/antagonists, adenylyl cyclase and PKAI inhibitors, T cell migration assay on ICAM-1 surfaces Journal of immunology Medium 24227782
2022 KCa3.1 is present in the inner mitochondrial membrane (mitoKCa3.1) in cancer cells. Mitochondria-targeted TRAM-34 derivatives that block mitoKCa3.1 induce mitochondrial ROS release, membrane depolarization, and mitochondrial network fragmentation, triggering cancer cell death. Plasma-membrane-impermeant Maurotoxin has no effect, confirming the mitochondrial channel is the relevant target. At sub-lethal concentrations, mitoKCa3.1 inhibition reduces cancer cell migration via NF-κB activation, BNIP-3 downregulation, and CDC-42-mediated cytoskeletal reorganization. Mitochondria-targeted drug synthesis, Maurotoxin (membrane-impermeant blocker), mitochondrial membrane potential assay, ROS measurement, NF-κB reporter, BNIP-3/CDC-42 manipulation, orthotopic in vivo cancer models Cell death & disease Medium 36539400
2014 NOX5-derived ROS are required for bFGF-induced upregulation of KCNN4 mRNA and protein in porcine coronary smooth muscle cells. NOX5 knockdown prevents KCNN4 upregulation and CSMC migration; the mechanism involves NOX5→superoxide→AP-1 transcriptional activation. siRNA knockdown of individual NOX isoforms, dihydroethidium fluorography, AP-1 luciferase reporter, qRT-PCR, immunohistochemistry, patch-clamp, migration assay PloS one Medium 25144362
2017 KCa3.1 regulates Ca2+-dependent NFATc1 expression during osteoclastogenesis via the CaMKIV/CREB/c-fos pathway. KCa3.1-/- and TRAM-34 treatment reduce RANKL-induced Ca2+ transient amplitudes (~50%), prevent CaMKIV phosphorylation, decrease CREB and c-fos, and reduce NFATc1 expression and osteoclast formation. KCa3.1 knockout BMMs, TRAM-34, live-cell Ca2+ imaging, Western blot (CaMKIV, CREB, c-fos, NFATc1), osteoclast differentiation assay Journal of immunology Medium 29246953

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 hSK4, a member of a novel subfamily of calcium-activated potassium channels. Proceedings of the National Academy of Sciences of the United States of America 315 9380751
1997 A novel gene, hKCa4, encodes the calcium-activated potassium channel in human T lymphocytes. The Journal of biological chemistry 250 9407042
2008 The intermediate-conductance calcium-activated potassium channel KCa3.1 contributes to atherogenesis in mice and humans. The Journal of clinical investigation 203 18688283
1999 hSK4/hIK1, a calmodulin-binding KCa channel in human T lymphocytes. Roles in proliferation and volume regulation. The Journal of biological chemistry 198 10329683
2008 Modulation of endothelial cell KCa3.1 channels during endothelium-derived hyperpolarizing factor signaling in mesenteric resistance arteries. Circulation research 188 18403729
2007 The Ca2+-activated K+ channel KCNN4/KCa3.1 contributes to microglia activation and nitric oxide-dependent neurodegeneration. The Journal of neuroscience : the official journal of the Society for Neuroscience 188 17202491
2010 Therapeutic potential of KCa3.1 blockers: recent advances and promising trends. Expert review of clinical pharmacology 170 22111618
2006 Histidine phosphorylation of the potassium channel KCa3.1 by nucleoside diphosphate kinase B is required for activation of KCa3.1 and CD4 T cells. Molecular cell 170 17157250
2004 Physiological roles of the intermediate conductance, Ca2+-activated potassium channel Kcnn4. The Journal of biological chemistry 163 15347667
2019 GABRP regulates chemokine signalling, macrophage recruitment and tumour progression in pancreatic cancer through tuning KCNN4-mediated Ca2+ signalling in a GABA-independent manner. Gut 159 30826748
2016 Differential Kv1.3, KCa3.1, and Kir2.1 expression in "classically" and "alternatively" activated microglia. Glia 134 27696527
2009 Renal fibrosis is attenuated by targeted disruption of KCa3.1 potassium channels. Proceedings of the National Academy of Sciences of the United States of America 133 19706538
2010 Inhibition of the K+ channel KCa3.1 ameliorates T cell-mediated colitis. Proceedings of the National Academy of Sciences of the United States of America 129 20080610
2013 KCa3.1 channels are involved in the infiltrative behavior of glioblastoma in vivo. Cell death & disease 115 23949222
2006 Functional KCa3.1 K+ channels are required for human lung mast cell migration. Thorax 111 16809411
2003 The hSK4 (KCNN4) isoform is the Ca2+-activated K+ channel (Gardos channel) in human red blood cells. Proceedings of the National Academy of Sciences of the United States of America 106 12773623
2008 Protein histidine phosphatase 1 negatively regulates CD4 T cells by inhibiting the K+ channel KCa3.1. Proceedings of the National Academy of Sciences of the United States of America 101 18796614
2015 Mutations in the Gardos channel (KCNN4) are associated with hereditary xerocytosis. Blood 100 26198474
2011 The Lymphocyte Potassium Channels Kv1.3 and KCa3.1 as Targets for Immunosuppression. Drug development research 99 22241939
2011 The KCa3.1 blocker TRAM-34 reduces infarction and neurological deficit in a rat model of ischemia/reperfusion stroke. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 95 21750563
2017 Potassium channels Kv1.3 and KCa3.1 cooperatively and compensatorily regulate antigen-specific memory T cell functions. Nature communications 94 28248292
2013 Bradykinin-induced chemotaxis of human gliomas requires the activation of KCa3.1 and ClC-3. The Journal of neuroscience : the official journal of the Society for Neuroscience 81 23345219
2013 Blockade of KCa3.1 ameliorates renal fibrosis through the TGF-β1/Smad pathway in diabetic mice. Diabetes 81 23656889
2015 The potassium channel KCa3.1 constitutes a pharmacological target for neuroinflammation associated with ischemia/reperfusion stroke. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 80 26661208
2012 KCa3.1 and TRPM7 channels at the uropod regulate migration of activated human T cells. PloS one 77 22952790
2012 The inhibition of KCa3.1 channels activity reduces cell motility in glioblastoma derived cancer stem cells. PloS one 77 23110108
2016 Role of KCa3.1 Channels in Macrophage Polarization and Its Relevance in Atherosclerotic Plaque Instability. Arteriosclerosis, thrombosis, and vascular biology 70 28062499
2011 Inhibition of the Ca²⁺-dependent K⁺ channel, KCNN4/KCa3.1, improves tissue protection and locomotor recovery after spinal cord injury. The Journal of neuroscience : the official journal of the Society for Neuroscience 68 22072681
2016 KCa3.1 inhibition switches the phenotype of glioma-infiltrating microglia/macrophages. Cell death & disease 67 27054329
2007 KCa3.1 Ca2+ activated K+ channels regulate human airway smooth muscle proliferation. American journal of respiratory cell and molecular biology 67 17585114
2022 Dextran sodium sulfate potentiates NLRP3 inflammasome activation by modulating the KCa3.1 potassium channel in a mouse model of colitis. Cellular & molecular immunology 63 35799057
2016 KCa3.1 mediates dysfunction of tubular autophagy in diabetic kidneys via PI3k/Akt/mTOR signaling pathways. Scientific reports 62 27029904
2014 Blood-brain barrier KCa3.1 channels: evidence for a role in brain Na uptake and edema in ischemic stroke. Stroke 62 25477223
2005 Phosphatidylinositol 3-phosphate indirectly activates KCa3.1 via 14 amino acids in the carboxy terminus of KCa3.1. Molecular biology of the cell 62 16251351
2016 Histidine phosphorylation relieves copper inhibition in the mammalian potassium channel KCa3.1. eLife 61 27542194
2008 KCa3.1 potassium channels are critical for cAMP-dependent chloride secretion and cyst growth in autosomal-dominant polycystic kidney disease. Kidney international 61 18547995
2014 IL-4 type 1 receptor signaling up-regulates KCNN4 expression, and increases the KCa3.1 current and its contribution to migration of alternative-activated microglia. Frontiers in cellular neuroscience 59 25071444
2019 Repurposing the KCa3.1 inhibitor senicapoc for Alzheimer's disease. Annals of clinical and translational neurology 57 31019997
2019 Junctophilin Proteins Tether a Cav1-RyR2-KCa3.1 Tripartite Complex to Regulate Neuronal Excitability. Cell reports 57 31461656
2013 Selective activation of KCa3.1 and CRAC channels by P2Y2 receptors promotes Ca(2+) signaling, store refilling and migration of rat microglial cells. PloS one 57 23620825
2012 Expression and Role of the Intermediate-Conductance Calcium-Activated Potassium Channel KCa3.1 in Glioblastoma. Journal of signal transduction 57 22675627
2016 miR-497-5p inhibits cell proliferation and invasion by targeting KCa3.1 in angiosarcoma. Oncotarget 56 27531900
2014 Kcnn4 is a regulator of macrophage multinucleation in bone homeostasis and inflammatory disease. Cell reports 54 25131209
2013 Selective inhibition of KCa3.1 channels mediates adenosine regulation of the motility of human T cells. Journal of immunology (Baltimore, Md. : 1950) 54 24227782
2008 Inhibition of the KCa3.1 channels by AMP-activated protein kinase in human airway epithelial cells. American journal of physiology. Cell physiology 53 19052260
2023 KCNN4 links PIEZO-dependent mechanotransduction to NLRP3 inflammasome activation. Science immunology 52 38134241
2013 Blocking KCa3.1 channels increases tumor cell killing by a subpopulation of human natural killer lymphocytes. PloS one 52 24146918
2016 KCa3.1 channel inhibition sensitizes malignant gliomas to temozolomide treatment. Oncotarget 50 27096953
2013 KCNN4 channels participate in the EMT induced by PRL-3 in colorectal cancer. Medical oncology (Northwood, London, England) 49 23572150
2013 Globotriaosylceramide induces lysosomal degradation of endothelial KCa3.1 in fabry disease. Arteriosclerosis, thrombosis, and vascular biology 49 24158513
2013 KCa3.1 mediates activation of fibroblasts in diabetic renal interstitial fibrosis. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 49 24166472
2019 Macrophages facilitate post myocardial infarction arrhythmias: roles of gap junction and KCa3.1. Theranostics 48 31588225
2014 Increased constitutive αSMA and Smad2/3 expression in idiopathic pulmonary fibrosis myofibroblasts is KCa3.1-dependent. Respiratory research 48 25476248
2013 Immunosuppression by N-methyl-D-aspartate receptor antagonists is mediated through inhibition of Kv1.3 and KCa3.1 channels in T cells. Molecular and cellular biology 48 24344200
2013 The K+ channel KCa3.1 as a novel target for idiopathic pulmonary fibrosis. PloS one 48 24392001
2018 KCa3.1 Channels and Glioblastoma: In Vitro Studies. Current neuropharmacology 46 28786347
2010 KCNN4 gene variant is associated with ileal Crohn's Disease in the Australian and New Zealand population. The American journal of gastroenterology 44 20407432
2019 KCNN4 promotes invasion and metastasis through the MAPK/ERK pathway in hepatocellular carcinoma. Journal of investigative medicine : the official publication of the American Federation for Clinical Research 43 31431469
2012 KCa3.1 channels mediate the increase of cell migration and proliferation by advanced glycation endproducts in cultured rat vascular smooth muscle cells. Laboratory investigation; a journal of technical methods and pathology 43 23212096
2009 The intermediate-conductance Ca2+ -activated K+ channel (KCa3.1) in vascular disease. Cardiovascular & hematological agents in medicinal chemistry 43 19149539
2018 KCa3.1 ion channel: A novel therapeutic target for corneal fibrosis. PloS one 42 29554088
2015 Human lung myofibroblast TGFβ1-dependent Smad2/3 signalling is Ca(2+)-dependent and regulated by KCa3.1 K(+) channels. Fibrogenesis & tissue repair 42 25829947
2014 PKA reduces the rat and human KCa3.1 current, CaM binding, and Ca2+ signaling, which requires Ser332/334 in the CaM-binding C terminus. The Journal of neuroscience : the official journal of the Society for Neuroscience 42 25274816
2018 Role of KCa3.1 Channels in Modulating Ca2+ Oscillations during Glioblastoma Cell Migration and Invasion. International journal of molecular sciences 41 30274242
2009 Blockade of T-lymphocyte KCa3.1 and Kv1.3 channels as novel immunosuppression strategy to prevent kidney allograft rejection. Transplantation proceedings 41 19715983
2018 KCa3.1 Channel Modulators as Potential Therapeutic Compounds for Glioblastoma. Current neuropharmacology 40 28676010
2015 The Blockage of KCa3.1 Channel Inhibited Proliferation, Migration and Promoted Apoptosis of Human Hepatocellular Carcinoma Cells. Journal of Cancer 40 26078795
2019 The potassium channel KCa3.1 promotes cell proliferation by activating SKP2 and metastasis through the EMT pathway in hepatocellular carcinoma. International journal of cancer 39 30628729
2016 KCa3.1 constitutes a pharmacological target for astrogliosis associated with Alzheimer's disease. Molecular and cellular neurosciences 39 27567685
2014 Targeted inhibition of KCa3.1 attenuates TGF-β-induced reactive astrogliosis through the Smad2/3 signaling pathway. Journal of neurochemistry 39 24606313
2014 Neuronal expression of the intermediate conductance calcium-activated potassium channel KCa3.1 in the mammalian central nervous system. Pflugers Archiv : European journal of physiology 39 24797146
2013 Targeted inhibition of KCa3.1 channel attenuates airway inflammation and remodeling in allergic asthma. American journal of respiratory cell and molecular biology 37 23492185
2012 NADPH oxidase 2-derived superoxide downregulates endothelial KCa3.1 in preeclampsia. Free radical biology & medicine 37 23261940
2011 Functional KCa3.1 K+ channels are required for human fibrocyte migration. The Journal of allergy and clinical immunology 36 21872912
2015 Complementary roles of KCa3.1 channels and β1-integrin during alveolar epithelial repair. Respiratory research 31 26335442
2012 Trafficking of intermediate (KCa3.1) and small (KCa2.x) conductance, Ca(2+)-activated K(+) channels: a novel target for medicinal chemistry efforts? ChemMedChem 31 22887933
2019 KCa3.1 deficiency attenuates neuroinflammation by regulating an astrocyte phenotype switch involving the PI3K/AKT/GSK3β pathway. Neurobiology of disease 30 31470105
2018 Ca2+-dependent endoplasmic reticulum stress correlation with astrogliosis involves upregulation of KCa3.1 and inhibition of AKT/mTOR signaling. Journal of neuroinflammation 30 30442153
2017 Activity-Dependent Facilitation of CaV1.3 Calcium Channels Promotes KCa3.1 Activation in Hippocampal Neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 30 29038242
2015 Blockade of KCa3.1 Attenuates Left Ventricular Remodeling after Experimental Myocardial Infarction. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 30 26160442
2014 Upregulation of intermediate-conductance Ca2+-activated K+ channels (KCNN4) in porcine coronary smooth muscle requires NADPH oxidase 5 (NOX5). PloS one 30 25144362
2013 KCa3.1 modulates neuroblast migration along the rostral migratory stream (RMS) in vivo. Cerebral cortex (New York, N.Y. : 1991) 30 23585521
2011 Calcium-activated potassium channel KCa3.1 in lung dendritic cell migration. American journal of respiratory cell and molecular biology 30 21493782
2015 The role of KCa3.1 channels in cardiac fibrosis induced by pressure overload in rats. Pflugers Archiv : European journal of physiology 29 25715999
2014 Upregulation of KCa3.1 K(+) channel in mesenteric lymph node CD4(+) T lymphocytes from a mouse model of dextran sodium sulfate-induced inflammatory bowel disease. American journal of physiology. Gastrointestinal and liver physiology 29 24674776
2010 ESCRT-dependent targeting of plasma membrane localized KCa3.1 to the lysosomes. American journal of physiology. Cell physiology 29 20720181
2015 KCa3.1/IK1 Channel Regulation by cGMP-Dependent Protein Kinase (PKG) via Reactive Oxygen Species and CaMKII in Microglia: An Immune Modulating Feedback System? Frontiers in immunology 28 25904916
2013 Functional KCa3.1 channels regulate steroid insensitivity in bronchial smooth muscle cells. Journal of immunology (Baltimore, Md. : 1950) 28 23904164
2013 Inhibition of KCa3.1 suppresses TGF-β1 induced MCP-1 expression in human proximal tubular cells through Smad3, p38 and ERK1/2 signaling pathways. The international journal of biochemistry & cell biology 28 24291552
2017 Ca2+-Dependent Regulation of NFATc1 via KCa3.1 in Inflammatory Osteoclastogenesis. Journal of immunology (Baltimore, Md. : 1950) 27 29246953
2010 Cloning and identification of tissue-specific expression of KCNN4 splice variants in rat colon. American journal of physiology. Cell physiology 27 20445171
2015 Functional role of the KCa3.1 potassium channel in synovial fibroblasts from rheumatoid arthritis patients. Journal of cellular physiology 26 25545021
2015 Orai/CRACM1 and KCa3.1 ion channels interact in the human lung mast cell plasma membrane. Cell communication and signaling : CCS 26 26177720
2013 Up-regulation of KCa3.1 promotes human airway smooth muscle cell phenotypic modulation. Pharmacological research 26 24055799
2016 KCNN4 and S100A14 act as predictors of recurrence in optimally debulked patients with serous ovarian cancer. Oncotarget 25 27270322
2022 Pharmacological targeting of the mitochondrial calcium-dependent potassium channel KCa3.1 triggers cell death and reduces tumor growth and metastasis in vivo. Cell death & disease 24 36539400
2016 The calcium-activated potassium channel KCa3.1 is an important modulator of hepatic injury. Scientific reports 24 27354175
2022 Regulatory role of KCa3.1 in immune cell function and its emerging association with rheumatoid arthritis. Frontiers in immunology 23 36275686
2019 Protein Kinase A-Mediated Suppression of the Slow Afterhyperpolarizing KCa3.1 Current in Temporal Lobe Epilepsy. The Journal of neuroscience : the official journal of the Society for Neuroscience 22 31672789
2013 Contribution of the KCa3.1 channel-calmodulin interactions to the regulation of the KCa3.1 gating process. The Journal of general physiology 22 23797421

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