Kcnn4

Summary

Gene Symbol: Kcnn4
Description: potassium intermediate/small conductance calcium-activated channel, subfamily N, member 4
Alias: IK1, IKCA1, KCA4, KCa3.1, SK4, SKCas, mIKCa1, intermediate conductance calcium-activated potassium channel protein 4, SKCa 4, SKCa4
Species: mouse
Products:     Kcnn4

Top Publications

  1. Grgic I, Kaistha B, Paschen S, Kaistha A, Busch C, Si H, et al. Disruption of the Gardos channel (KCa3.1) in mice causes subtle erythrocyte macrocytosis and progressive splenomegaly. Pflugers Arch. 2009;458:291-302 pubmed publisher
    ..We conclude that genetic deficit of erythroid K(Ca)3.1 causes mild RBC macrocytosis, presumably leading to reduced filterability, and impairs volume regulation. These RBC defects result in mild but progressive splenomegaly...
  2. Nehrke K, Quinn C, Begenisich T. Molecular identification of Ca2+-activated K+ channels in parotid acinar cells. Am J Physiol Cell Physiol. 2003;284:C535-46 pubmed
    ..consistent with the intermediate and maxi-K classes of Ca(2+)-activated K(+) channels, typified by the mIK1 (Kcnn4) and mSlo (Kcnma1) genes, respectively...
  3. Huang C, Shen S, Ma Q, Chen J, Gill A, Pollock C, et al. Blockade of KCa3.1 ameliorates renal fibrosis through the TGF-?1/Smad pathway in diabetic mice. Diabetes. 2013;62:2923-34 pubmed publisher
    ..1 mediates renal fibrosis in diabetic nephropathy through the TGF-?1/Smad signaling pathway. Blockade of KCa3.1 may be a novel target for therapeutic intervention in patients with diabetic nephropathy. ..
  4. Vandorpe D, Shmukler B, Jiang L, Lim B, Maylie J, Adelman J, et al. cDNA cloning and functional characterization of the mouse Ca2+-gated K+ channel, mIK1. Roles in regulatory volume decrease and erythroid differentiation. J Biol Chem. 1998;273:21542-53 pubmed
    ..Low nanomolar concentrations of CLT inhibited proliferation and erythroid differentiation of peripheral blood stem cells in liquid culture. ..
  5. Brähler S, Kaistha A, Schmidt V, Wölfle S, Busch C, Kaistha B, et al. Genetic deficit of SK3 and IK1 channels disrupts the endothelium-derived hyperpolarizing factor vasodilator pathway and causes hypertension. Circulation. 2009;119:2323-32 pubmed publisher
    It has been proposed that activation of endothelial SK3 (K(Ca)2.3) and IK1 (K(Ca)3.1) K+ channels plays a role in the arteriolar dilation attributed to an endothelium-derived hyperpolarizing factor (EDHF)...
  6. Wölfle S, Schmidt V, Hoyer J, Köhler R, de Wit C. Prominent role of KCa3.1 in endothelium-derived hyperpolarizing factor-type dilations and conducted responses in the microcirculation in vivo. Cardiovasc Res. 2009;82:476-83 pubmed publisher
    ..3. Sole activation of KCa3.1 is capable of initiating conducted responses, and KCa3.1 may contribute to the propagation of the signal, although its presence is not mandatory. ..
  7. Lambertsen K, Gramsbergen J, Sivasaravanaparan M, Ditzel N, Sevelsted Møller L, Oliván Viguera A, et al. Genetic KCa3.1-deficiency produces locomotor hyperactivity and alterations in cerebral monoamine levels. PLoS ONE. 2012;7:e47744 pubmed publisher
    ..The tranquilizing effects of low-dose SKA-31 raise the possibility to use KCa3.1/KCa2 channels as novel pharmacological targets for the treatment of neuropsychiatric hyperactivity disorders. ..
  8. Grgic I, Wulff H, Eichler I, Flothmann C, Kohler R, Hoyer J. Blockade of T-lymphocyte KCa3.1 and Kv1.3 channels as novel immunosuppression strategy to prevent kidney allograft rejection. Transplant Proc. 2009;41:2601-6 pubmed publisher
    ..Thus, selective blockade of T-lymphocyte K(Ca)3.1 and K(v)1.3 channels may represent a novel alternative therapy for prevention of kidney allograft rejection. ..
  9. Hua X, Deuse T, Chen Y, Wulff H, Stubbendorff M, Köhler R, et al. The potassium channel KCa3.1 as new therapeutic target for the prevention of obliterative airway disease. Transplantation. 2013;95:285-92 pubmed publisher
    ..1 splenocytes. Our findings suggest that KCa3.1 channels are involved in the pathogenesis of OAD and that KCa3.1 blockade holds promise to reduce OAD development. ..

More Information

Publications81

  1. Tao R, Lau C, Tse H, Li G. Regulation of cell proliferation by intermediate-conductance Ca2+-activated potassium and volume-sensitive chloride channels in mouse mesenchymal stem cells. Am J Physiol Cell Physiol. 2008;295:C1409-16 pubmed publisher
    ..Collectively, our results have demonstrated that IK(Ca) and I(Cl.vol) channels regulate cell cycle progression and proliferation of mouse MSCs by modulating cyclin D1 and cyclin E expression. ..
  2. Toyama K, Wulff H, Chandy K, Azam P, Raman G, Saito T, et al. The intermediate-conductance calcium-activated potassium channel KCa3.1 contributes to atherogenesis in mice and humans. J Clin Invest. 2008;118:3025-37 pubmed publisher
    ..These data suggest that KCa3.1 blockers represent a promising therapeutic strategy for atherosclerosis. ..
  3. Shumilina E, Lam R, Wölbing F, Matzner N, Zemtsova I, Sobiesiak M, et al. Blunted IgE-mediated activation of mast cells in mice lacking the Ca2+-activated K+ channel KCa3.1. J Immunol. 2008;180:8040-7 pubmed
    ..In conclusion, K(Ca)3.1 is required for Ca(2+)-activated K(+) channel activity and Ca(2+)-dependent processes such as endothelin-1- or Ag-induced degranulation of mast cells, and may thus play a critical role in anaphylactic reactions. ..
  4. Tamarina N, Wang Y, Mariotto L, Kuznetsov A, Bond C, Adelman J, et al. Small-conductance calcium-activated K+ channels are expressed in pancreatic islets and regulate glucose responses. Diabetes. 2003;52:2000-6 pubmed
    ..We conclude that SK1, -2, -3, and IK1 (SK4) are expressed in islet cells and insulin-secreting cells and are able to influence glucose-induced calcium ..
  5. Begenisich T, Nakamoto T, Ovitt C, Nehrke K, Brugnara C, Alper S, et al. Physiological roles of the intermediate conductance, Ca2+-activated potassium channel Kcnn4. J Biol Chem. 2004;279:47681-7 pubmed
    ..are likely encoded by three genes, Kcnn1-3, whereas IK and most BK channels are most likely products of the Kcnn4 and Slo (Kcnma1) genes, respectively...
  6. Sausbier M, Matos J, Sausbier U, Beranek G, Arntz C, Neuhuber W, et al. Distal colonic K(+) secretion occurs via BK channels. J Am Soc Nephrol. 2006;17:1275-82 pubmed
    ..was not altered in mice that were deficient for the intermediate conductance Ca(2+)-activated K(+) channel SK4. BK channels localize to the luminal membrane of crypt, and reverse transcription-PCR results confirm the ..
  7. Park S, Kim J, Joo K, Choi S, Choi E, Shin J, et al. Globotriaosylceramide leads to K(Ca)3.1 channel dysfunction: a new insight into endothelial dysfunction in Fabry disease. Cardiovasc Res. 2011;89:290-9 pubmed publisher
    ..Gb3 thereby evokes K(Ca)3.1 channel dysfunction, and the channel dysfunction in vascular endothelial cells may contribute to vasculopathy in Fabry disease. ..
  8. Di L, Srivastava S, Zhdanova O, Ding Y, Li Z, Wulff H, et al. Inhibition of the K+ channel KCa3.1 ameliorates T cell-mediated colitis. Proc Natl Acad Sci U S A. 2010;107:1541-6 pubmed publisher
    ..Thus, if these preclinical studies continue to show efficacy, it may be possible to rapidly test whether KCa3.1 inhibitors are efficacious in patients with inflammatory bowel diseases such as Crohn's disease and ulcerative colitis. ..
  9. Si H, Heyken W, Wölfle S, Tysiac M, Schubert R, Grgic I, et al. Impaired endothelium-derived hyperpolarizing factor-mediated dilations and increased blood pressure in mice deficient of the intermediate-conductance Ca2+-activated K+ channel. Circ Res. 2006;99:537-44 pubmed
    ..1 is a fundamental determinant of endothelial hyperpolarization and EDHF signaling and, thereby, a crucial determinant in the control of vascular tone and overall circulatory regulation. ..
  10. Huang C, Shen S, Ma Q, Gill A, Pollock C, Chen X. KCa3.1 mediates activation of fibroblasts in diabetic renal interstitial fibrosis. Nephrol Dial Transplant. 2014;29:313-24 pubmed publisher
    ..Therefore, therapeutic interventions to prevent or ameliorate DN through targeted inhibition of KCa3.1 deserve further consideration. ..
  11. Grgic I, Kiss E, Kaistha B, Busch C, Kloss M, Sautter J, et al. Renal fibrosis is attenuated by targeted disruption of KCa3.1 potassium channels. Proc Natl Acad Sci U S A. 2009;106:14518-23 pubmed publisher
    ..In conclusion, our data demonstrate that K(Ca)3.1 is involved in renal fibroblast proliferation and fibrogenesis and suggest that K(Ca)3.1 may represent a therapeutic target for the treatment of fibrotic kidney disease. ..
  12. Taylor S, Gonzalez Begne M, Dewhurst S, Chimini G, Higgins C, Melvin J, et al. Sequential shrinkage and swelling underlie P2X7-stimulated lymphocyte phosphatidylserine exposure and death. J Immunol. 2008;180:300-8 pubmed
    ..The mixed apoptotic/necrotic phenotype of P2X7-stimulated cells is consistent with a potential role for this death pathway in lupus disease. ..
  13. Zhang X, Zhang Y, Sun H, Jin M, Li G. Functional ion channels and cell proliferation in 3T3-L1 preadipocytes. J Cell Physiol. 2012;227:1972-9 pubmed publisher
    ..These results demonstrate that three functional ion channel currents, I(KCa), I(Cl.vol), and I(Kir), are heterogeneously present in 3T3-L1 preadipocytes. I(KCa) and I(Cl.vol) participate in the regulation of cell proliferation. ..
  14. Yu Z, Xu J, Wang Y, Xu G, Xu Z, Yang K, et al. Targeted inhibition of KCa3.1 channel attenuates airway inflammation and remodeling in allergic asthma. Am J Respir Cell Mol Biol. 2013;48:685-93 pubmed publisher
    ..We demonstrate for the first time an important role for KCa3.1 in the pathogenesis of airway inflammation and remodeling in allergic asthma, and we suggest that KCa3.1 blockers may represent a promising therapeutic strategy for asthma. ..
  15. Nakamoto T, Romanenko V, Takahashi A, Begenisich T, Melvin J. Apical maxi-K (KCa1.1) channels mediate K+ secretion by the mouse submandibular exocrine gland. Am J Physiol Cell Physiol. 2008;294:C810-9 pubmed publisher
    ..1) but was unchanged in mice lacking the intermediate-conductance IKCa1 channel (KCa3.1)...
  16. Romanenko V, Nakamoto T, Srivastava A, Melvin J, Begenisich T. Molecular identification and physiological roles of parotid acinar cell maxi-K channels. J Biol Chem. 2006;281:27964-72 pubmed
    ..Parotid acinar cells express two types of Ca(2+)-activated K(+) channels: intermediate conductance IK1 channels and maxi-K channels. The IK1 channel is encoded by the K(Ca)3.1 gene, and the K(Ca)1...
  17. Yu Z, Yu P, Chen H, Geller H. Targeted inhibition of KCa3.1 attenuates TGF-β-induced reactive astrogliosis through the Smad2/3 signaling pathway. J Neurochem. 2014;130:41-49 pubmed publisher
    ..We demonstrate that either pharmacological blockade or knockout of KCa3.1 channels reduces reactive gliosis in cultured astrocytes caused by TGF-β, and also reduces TGF-β-induced phosphorylation of Smad2/3. ..
  18. Ruggieri P, Mangino G, Fioretti B, Catacuzzeno L, Puca R, Ponti D, et al. The inhibition of KCa3.1 channels activity reduces cell motility in glioblastoma derived cancer stem cells. PLoS ONE. 2012;7:e47825 pubmed publisher
    ..Because invasion of surrounding tissues is one of the main causes of treatment failure in glioblastoma, these findings can be relevant for future development of novel cancer therapeutic drugs. ..
  19. Ledoux J, Bonev A, Nelson M. Ca2+-activated K+ channels in murine endothelial cells: block by intracellular calcium and magnesium. J Gen Physiol. 2008;131:125-35 pubmed publisher
    ..These results indicate that [Ca(2+)](i) can both activate and block IK(Ca) and SK(Ca) channels in endothelial cells, and that these channels regulate the resting membrane potential and intracellular calcium in native endothelium. ..
  20. Choi S, Kim J, Na H, Cho S, Park S, Jung S, et al. Globotriaosylceramide induces lysosomal degradation of endothelial KCa3.1 in fabry disease. Arterioscler Thromb Vasc Biol. 2014;34:81-9 pubmed publisher
    ..1 expression, the current, and endothelium-dependent relaxation. -Gb3 accelerates the endocytosis and lysosomal degradation of endothelial KCa3.1 via a clathrin-dependent process, leading to endothelial dysfunction in FD. ..
  21. Warth R, Hamm K, Bleich M, Kunzelmann K, von Hahn T, Schreiber R, et al. Molecular and functional characterization of the small Ca(2+)-regulated K+ channel (rSK4) of colonic crypts. Pflugers Arch. 1999;438:437-44 pubmed
    ..This protein has a high homology to hSK4 and mouse IK1. These data indicate that the Ca(2+)-activated and imidazole-inhibited basolateral K+ current in the colon is caused by SK4 channels.
  22. Piao L, Li J, McLerie M, Lopatin A. Cardiac IK1 underlies early action potential shortening during hypoxia in the mouse heart. J Mol Cell Cardiol. 2007;43:27-38 pubmed
    ..Under normal conditions IK1 channels are constitutively active while K(ATP) channels are closed...
  23. Huang C, Pollock C, Chen X. High glucose induces CCL20 in proximal tubular cells via activation of the KCa3.1 channel. PLoS ONE. 2014;9:e95173 pubmed publisher
    ..1 channel in both animal models led to a reduction in phosphorylated NF-?B. Overexpression of CCL20 in human proximal tubular cells is inhibited by blockade of KCa3.1 under diabetic conditions through inhibition of the NF-?B pathway. ..
  24. Chen C, Liao J, Hu O, Pao L. Blockade of KCa3.1 potassium channels protects against cisplatin-induced acute kidney injury. Arch Toxicol. 2016;90:2249-2260 pubmed publisher
    ..1 blockade protects against cisplatin-induced AKI through the attenuation of apoptosis by interference with intrinsic apoptotic and ER stress-related mediators, providing a potential target for the prevention of cisplatin-induced AKI. ..
  25. Kahlfuß S, Simma N, Mankiewicz J, Bose T, Lowinus T, Klein Hessling S, et al. Immunosuppression by N-methyl-D-aspartate receptor antagonists is mediated through inhibition of Kv1.3 and KCa3.1 channels in T cells. Mol Cell Biol. 2014;34:820-31 pubmed publisher
    ..Hence, NMDAR antagonists are potent immunosuppressants with therapeutic potential in the treatment of immune diseases, but their effects on T cells have to be considered in that Kv1.3 and KCa3.1 channels are their major effectors. ..
  26. Thompson J, Begenisich T. Mechanistic details of BK channel inhibition by the intermediate conductance, Ca2+-activated K channel. Channels (Austin). 2009;3:194-204 pubmed
    ..cells have two types of Ca(2+)-activated K channels required for fluid secretion: the intermediate conductance (IK1) channel and the large conductance (BK) channel...
  27. Huang C, Lin M, Cheng D, Braet F, Pollock C, Chen X. KCa3.1 mediates dysfunction of tubular autophagy in diabetic kidneys via PI3k/Akt/mTOR signaling pathways. Sci Rep. 2016;6:23884 pubmed publisher
    ..1-/- mice. These results suggest that KCa3.1 activation contributes to dysfunctional tubular autophagy in diabetic nephropathy through PI3K/Akt/mTOR signaling pathways. ..
  28. Shao Z, Makinde T, Agrawal D. Calcium-activated potassium channel KCa3.1 in lung dendritic cell migration. Am J Respir Cell Mol Biol. 2011;45:962-8 pubmed publisher
    ..1 with TRAM-34 impaired CCL19/CCL21-induced transmigration. In conclusion, KCa3.1 expression in lung DCs is up-regulated by OVA sensitization in both lung DC subsets, and KCa3.1 is involved in lung DC migration to lymphatic chemokines. ..
  29. Wandall Frostholm C, Skaarup L, Sadda V, Nielsen G, Hedegaard E, Mogensen S, et al. Pulmonary hypertension in wild type mice and animals with genetic deficit in KCa2.3 and KCa3.1 channels. PLoS ONE. 2014;9:e97687 pubmed publisher
    ..3/KCa3.1 activators for the treatment of pulmonary hypertension. ..
  30. Yoo H, Zheng H, Nam J, Nguyen Y, Kang T, Earm Y, et al. Facilitation of Ca2+-activated K+ channels (IKCa1) by mibefradil in B lymphocytes. Pflugers Arch. 2008;456:549-60 pubmed publisher
    ..In the inside-out patch clamp study with cloned murine IKCa1 (mIKCa1) in HEK-293, mibefradil increased both Ca2+ sensitivity and maximum activity of mIKCa1...
  31. Milkau M, Köhler R, de Wit C. Crucial importance of the endothelial K+ channel SK3 and connexin40 in arteriolar dilations during skeletal muscle contraction. FASEB J. 2010;24:3572-9 pubmed publisher
    ..In EDHF signaling, endothelial hyperpolarization mediated by the Ca(2+)-activated K(+) channels SK3 and IK1 is a key step and also initiates gap junction-dependent conducted dilations...
  32. Li Y, Hu H, Tian J, Zhu M, O Neil R. Dynamic coupling between TRPV4 and Ca2+-activated SK1/3 and IK1 K+ channels plays a critical role in regulating the K+-secretory BK channel in kidney collecting duct cells. Am J Physiol Renal Physiol. 2017;312:F1081-F1089 pubmed publisher
    ..Ca2+-activated K+ channels, SK1 (KCNN1), SK3 (KCNN3), and IK1 (KCNN4), with notably high Ca2+-binding affinities, that are expressed in CNT/CCD and may be regulated by ..
  33. Tao R, Lau C, Tse H, Li G. Functional ion channels in mouse bone marrow mesenchymal stem cells. Am J Physiol Cell Physiol. 2007;293:C1561-7 pubmed
    ..These results demonstrate that three types of functional ion channel currents (i.e., I(Kir), I(KCa), and I(Cl)) are present in mouse bone marrow MSCs. ..
  34. Ohya S, Nakamura E, Horiba S, Kito H, Matsui M, Yamamura H, et al. Role of the K(Ca)3.1 K+ channel in auricular lymph node CD4+ T-lymphocyte function of the delayed-type hypersensitivity model. Br J Pharmacol. 2013;169:1011-23 pubmed publisher
    ..1a in conjunction with the down-regulation of REST may be involved in CD4(+) T-lymphocyte proliferation in the ALNs of DTH model mice; and K(Ca)3.1 may be an important target for therapeutic intervention in allergy diseases such as DTH. ..
  35. Liang Z, Chen L, McClafferty H, Lukowski R, MacGregor D, King J, et al. Control of hypothalamic-pituitary-adrenal stress axis activity by the intermediate conductance calcium-activated potassium channel, SK4. J Physiol. 2011;589:5965-86 pubmed publisher
    ..ACTH and corticosterone concentrations were significantly enhanced in gene-targeted mice lacking SK4 channels (Kcnn4(-/-))...
  36. King B, Rizwan A, Asmara H, Heath N, Engbers J, Dykstra S, et al. IKCa channels are a critical determinant of the slow AHP in CA1 pyramidal neurons. Cell Rep. 2015;11:175-82 pubmed
  37. Mattheij N, Braun A, van Kruchten R, Castoldi E, Pircher J, Baaten C, et al. Survival protein anoctamin-6 controls multiple platelet responses including phospholipid scrambling, swelling, and protein cleavage. FASEB J. 2016;30:727-37 pubmed publisher
    ..In conclusion, mouse deficiency of Ano6 but not of other channels affects viability and phenocopies the complex changes in platelets from hemostatically impaired patients with Scott syndrome. ..
  38. Choi S, Kim J, Li H, Shin K, Oh G, Lee Y, et al. KCa 3.1 upregulation preserves endothelium-dependent vasorelaxation during aging and oxidative stress. Aging Cell. 2016;15:801-10 pubmed publisher
    ..1 expression and function via a H2 O2 /Fyn-mediated pathway. Altogether, enhanced KCa 3.1 activity may compensate for decreased NO signaling during vascular aging. ..
  39. Yi M, Yu P, Lu Q, Geller H, Yu Z, Chen H. KCa3.1 constitutes a pharmacological target for astrogliosis associated with Alzheimer's disease. Mol Cell Neurosci. 2016;76:21-32 pubmed publisher
    ..We also found in astrocyte cultures that blockade of KCa3.1 or deletion of KCa3.1 suppressed Aβ oligomer-induced astrogliosis. Our data suggest that KCa3.1 inhibition might represent a promising therapeutic strategy for AD treatment. ..
  40. Rotte A, Pasham V, Mack A, Bhandaru M, Qadri S, Eichenmüller M, et al. Ca2+ activated K+ channel Kca3.1 as a determinant of gastric acid secretion. Cell Physiol Biochem. 2011;27:597-604 pubmed publisher
    ..1 opener DCEBIO (100 ?M) did not significantly alter basal ?pH/min but significantly blunted ?pH/min in the presence of carbachol. In conclusion, K(ca)3.1 activity suppresses carbachol stimulated gastric acid secretion. ..
  41. Ohya S, Niwa S, Yanagi A, Fukuyo Y, Yamamura H, Imaizumi Y. Involvement of dominant-negative spliced variants of the intermediate conductance Ca2+-activated K+ channel, K(Ca)3.1, in immune function of lymphoid cells. J Biol Chem. 2011;286:16940-52 pubmed publisher
  42. Domenighetti A, Boixel C, Cefai D, Abriel H, Pedrazzini T. Chronic angiotensin II stimulation in the heart produces an acquired long QT syndrome associated with IK1 potassium current downregulation. J Mol Cell Cardiol. 2007;42:63-70 pubmed
    ..The change in APD90 correlated with a reduction in IK1 potassium current density in TG vs. WT cardiomyocytes (at -70 mV: 0.3+/-0.1 pA/pF vs. 0.8+/-0.2 pA/pF, P<0.05)...
  43. Lam R, Nahirney D, Duszyk M. Cholesterol-dependent regulation of adenosine A(2A) receptor-mediated anion secretion in colon epithelial cells. Exp Cell Res. 2009;315:3028-35 pubmed publisher
    ..more potently than adenosine, and the current was inhibited by clotrimazole, an inhibitor of Ca(2+)-activated K(+) (IK1) channels...
  44. Wang K, Kelley M, Wu W, Adelman J, Maylie J. Apamin Boosting of Synaptic Potentials in CaV2.3 R-Type Ca2+ Channel Null Mice. PLoS ONE. 2015;10:e0139332 pubmed publisher
    ..2-containing channels to CaV2.3 channels to provide negative feedback regulation of EPSPs in the spines of CA1 pyramidal neurons. ..
  45. Zhou X, Feng Y, Sun Q, Lukowski R, Qiu Y, Spiger K, et al. Nucleoside diphosphate kinase B-activated intermediate conductance potassium channels are critical for neointima formation in mouse carotid arteries. Arterioscler Thromb Vasc Biol. 2015;35:1852-61 pubmed publisher
    ..The intermediate conductance Ca(2+)-activated K(+) (SK4) channel is required for pathological VSMC proliferation...
  46. Flores C, Melvin J, Figueroa C, Sepúlveda F. Abolition of Ca2+-mediated intestinal anion secretion and increased stool dehydration in mice lacking the intermediate conductance Ca2+-dependent K+ channel Kcnn4. J Physiol. 2007;583:705-17 pubmed
    ..We have now used a Kcnn4 null mouse to show that the intermediate conductance IK1 K(+) channel is necessary and sufficient to support Ca(2+)..
  47. Nguyen H, Grössinger E, Horiuchi M, Davis K, Jin L, Maezawa I, et al. Differential Kv1.3, KCa3.1, and Kir2.1 expression in "classically" and "alternatively" activated microglia. Glia. 2017;65:106-121 pubmed publisher
    ..This differential K+ channel expression pattern suggests that KV 1.3 and KCa 3.1 inhibitors could be used to inhibit detrimental neuroinflammatory microglia functions. GLIA 2016;65:106-121. ..
  48. Maekawa M, Terasaka S, Mochizuki Y, Kawai K, Ikeda Y, Araki N, et al. Sequential breakdown of 3-phosphorylated phosphoinositides is essential for the completion of macropinocytosis. Proc Natl Acad Sci U S A. 2014;111:E978-87 pubmed publisher
    ..We propose that the sequential breakdown of PI(3,4,5)P3 ? PI(3,4)P2 ? PI(3)P ? PI controls macropinocytosis through specific effectors of the intermediate phosphoinositides. ..
  49. Thompson J, Begenisich T. Membrane-delimited inhibition of maxi-K channel activity by the intermediate conductance Ca2+-activated K channel. J Gen Physiol. 2006;127:159-69 pubmed
    ..1 gene, and IK1 channels (KCa3.1)...
  50. Turner K, Sontheimer H. KCa3.1 modulates neuroblast migration along the rostral migratory stream (RMS) in vivo. Cereb Cortex. 2014;24:2388-400 pubmed publisher
    ..1 in vivo. These studies describe a previously unrecognized protein in migration of adult NPCs. ..
  51. Lin M, Adelman J, Maylie J. Modulation of endothelial SK3 channel activity by Ca²+dependent caveolar trafficking. Am J Physiol Cell Physiol. 2012;303:C318-27 pubmed publisher
    Small- and intermediate-conductance Ca(2+)-activated K(+) channels (SK3/Kcnn3 and IK1/Kcnn4) are expressed in vascular endothelium...
  52. Srivastava U, Aromolaran A, Fabris F, Lazaro D, Kassotis J, Qu Y, et al. Novel function of ?1D L-type calcium channel in the atria. Biochem Biophys Res Commun. 2017;482:771-776 pubmed publisher
    ..The decrease in ?1D mRNA corresponded with a 4.2 fold decrease in Kcnn4 (gene encoding SK4) mRNA from ?1D+/- mice...
  53. Anumanthan G, Gupta S, Fink M, Hesemann N, Bowles D, McDaniel L, et al. KCa3.1 ion channel: A novel therapeutic target for corneal fibrosis. PLoS ONE. 2018;13:e0192145 pubmed publisher
    ..Our study suggests that KCa3.1 regulates corneal wound healing and that blockade of KCa3.1 by TRAM-34 offers a potential therapeutic strategy for developing therapies to cure corneal fibrosis in vivo. ..
  54. Romanenko V, Nakamoto T, Srivastava A, Begenisich T, Melvin J. Regulation of membrane potential and fluid secretion by Ca2+-activated K+ channels in mouse submandibular glands. J Physiol. 2007;581:801-17 pubmed
    We have recently shown that the IK1 and maxi-K channels in parotid salivary gland acinar cells are encoded by the K(Ca)3.1 and K(Ca)1.1 genes, respectively, and in vivo stimulated parotid secretion is severely reduced in double-null mice...
  55. Yi M, Dou F, Lu Q, Yu Z, Chen H. Activation of the KCa3.1 channel contributes to traumatic scratch injury-induced reactive astrogliosis through the JNK/c-Jun signaling pathway. Neurosci Lett. 2016;624:62-71 pubmed publisher
    ..1 in phenotypic modulation of reactive astrocytes and in astrocyte mobilization in response to mechanical stress, providing a potential target for therapeutic intervention in brain injuries. ..
  56. Grimaldi A, D Alessandro G, Golia M, Grössinger E, Di Angelantonio S, Ragozzino D, et al. KCa3.1 inhibition switches the phenotype of glioma-infiltrating microglia/macrophages. Cell Death Dis. 2016;7:e2174 pubmed publisher
    ..1. Anti-inflammatory M/M? have higher expression levels of KCa3.1 mRNA (kcnn4) that are reduced by KCa3.1 inhibition...
  57. Xu R, Li C, Wu Y, Shen L, Ma J, Qian J, et al. Role of KCa3.1 Channels in Macrophage Polarization and Its Relevance in Atherosclerotic Plaque Instability. Arterioscler Thromb Vasc Biol. 2017;37:226-236 pubmed publisher
    ..These results suggest that blocking KCa3.1 suppresses plaque instability in advanced stages of atherosclerosis by inhibiting macrophage polarization toward an M1 phenotype. ..
  58. Choi J, Park S. Role of protein kinase A and class II phosphatidylinositol 3-kinase C2β in the downregulation of KCa3.1 channel synthesis and membrane surface expression by lyso-globotriaosylceramide. Biochem Biophys Res Commun. 2016;470:907-12 pubmed publisher
    ..1 channel expression can be an alternative important target to attenuate ascending thoracic aortic aneurysms in Fabry disease. ..
  59. Zhang S, Wang X, Ju C, Zhu L, Du Y, Gao C. Blockage of K(Ca)3.1 and Kv1.3 channels of the B lymphocyte decreases the inflammatory monocyte chemotaxis. Int Immunopharmacol. 2016;31:266-71 pubmed publisher
    ..The opening of KCa3.1 and Kv1.3 channels promote B lymphocyte activation, proliferation and Ly-6C(hi) monocyte chemotaxis. The increase of CCL7 secretion by B lymphocyte may explain the pro migration effects. ..
  60. Wang K, Mateos Aparicio P, Hönigsperger C, Raghuram V, Wu W, Ridder M, et al. IK1 channels do not contribute to the slow afterhyperpolarization in pyramidal neurons. elife. 2016;5:e11206 pubmed publisher
    ..identity of which has remained elusive until a recent report suggested the Ca(2+)-activated K(+) channel, IK1 (KCNN4) as the sAHP channel in CA1 pyramidal neurons...
  61. Foller M, Bobbala D, Koka S, Boini K, Mahmud H, Kasinathan R, et al. Functional significance of the intermediate conductance Ca2+-activated K+ channel for the short-term survival of injured erythrocytes. Pflugers Arch. 2010;460:1029-44 pubmed publisher
    ..1 and transient shrinkage of the infected erythrocytes. In conclusion, K(Ca)3.1 channel activity and Gardos effect counteract hemolysis of injured erythrocytes, thus decreasing hemoglobin release into circulating blood. ..
  62. Marquard J, Otter S, Welters A, Stirban A, Fischer A, Eglinger J, et al. Characterization of pancreatic NMDA receptors as possible drug targets for diabetes treatment. Nat Med. 2015;21:363-72 pubmed publisher
    ..Our data highlight the possibility that antagonists of NMDARs may provide a useful adjunct treatment for diabetes. ..
  63. Kleger A, Seufferlein T, Malan D, Tischendorf M, Storch A, Wolheim A, et al. Modulation of calcium-activated potassium channels induces cardiogenesis of pluripotent stem cells and enrichment of pacemaker-like cells. Circulation. 2010;122:1823-36 pubmed publisher
    ..Earlier work identified Ca(2+)-activated potassium channels of small and intermediate conductance (SKCas) as important regulators of neural stem cell fate...
  64. Ohya S, Fukuyo Y, Kito H, Shibaoka R, Matsui M, Niguma H, et al. 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. Am J Physiol Gastrointest Liver Physiol. 2014;306:G873-85 pubmed publisher
    The intermediate-conductance Ca(2+)-activated K(+) channel KCa3.1/KCNN4 plays an important role in the modulation of Ca(2+) signaling through the control of the membrane potential in T lymphocytes. Here, we study the involvement of KCa3...
  65. Choi S, Kim M, Joo K, Park S, Kim J, Jung J, et al. Modafinil inhibits K(Ca)3.1 currents and muscle contraction via a cAMP-dependent mechanism. Pharmacol Res. 2012;66:51-9 pubmed publisher
    ..1 channels and vascular smooth muscle contraction by cAMP-dependent phosphorylation, suggesting that modafinil can be used as a cAMP-dependent K(Ca)3.1 channel blocker and vasodilator. ..
  66. Henríquez C, Riquelme T, Vera D, Julio Kalajzić F, Ehrenfeld P, Melvin J, et al. The calcium-activated potassium channel KCa3.1 plays a central role in the chemotactic response of mammalian neutrophils. Acta Physiol (Oxf). 2016;216:132-45 pubmed publisher
    ..These results demonstrate that KCa3.1 channels are key actors in the migration capacity of neutrophils, and its inhibition did not affect other relevant cellular functions. ..
  67. Di L, Srivastava S, Zhdanova O, Sun Y, Li Z, Skolnik E. Nucleoside diphosphate kinase B knock-out mice have impaired activation of the K+ channel KCa3.1, resulting in defective T cell activation. J Biol Chem. 2010;285:38765-71 pubmed publisher
  68. Dominguez Rieg J, Burt J, Ruth P, Rieg T. P2Yâ‚‚ receptor activation decreases blood pressure via intermediate conductance potassium channels and connexin 37. Acta Physiol (Oxf). 2015;213:628-41 pubmed publisher
    ..The data suggest that the P2Y2/4 receptor activation elicits blood pressure responses via distinct mechanisms involving KCa3.1 and Cx37. ..
  69. Kacik M, Oliván Viguera A, Köhler R. Modulation of K(Ca)3.1 channels by eicosanoids, omega-3 fatty acids, and molecular determinants. PLoS ONE. 2014;9:e112081 pubmed publisher
    ..From the physiological perspective, metabolism of AA to non-blocking 5,6,- and 8,9-EET may cause AA-de-blockade and contribute to cellular signal transduction processes influenced by these fatty acids. ..
  70. Drews G. Physiological significance of SK4 channels in pancreatic ?-cell oscillations. Islets. 2009;1:148-50 pubmed publisher
    ..1 or IK1) also contributes to the Kslow current...
  71. Qian X, Francis M, Köhler R, Solodushko V, Lin M, Taylor M. Positive feedback regulation of agonist-stimulated endothelial Ca2+ dynamics by KCa3.1 channels in mouse mesenteric arteries. Arterioscler Thromb Vasc Biol. 2014;34:127-35 pubmed publisher
    Intermediate and small conductance KCa channels IK1 (KCa3.1) and SK3 (KCa2.3) are primary targets of endothelial Ca(2+) signals in the arterial vasculature, and their ablation results in increased arterial tone and hypertension...
  72. Schmidt E, Münzer P, Borst O, Kraemer B, Schmid E, Urban B, et al. Ion channels in the regulation of platelet migration. Biochem Biophys Res Commun. 2011;415:54-60 pubmed publisher
    ..were isolated from human volunteers as well as from gene targeted mice lacking the Ca(2+) activated K(+) channel SK4 (sk4(-/-)) and their wild type littermates (sk4(+/+))...