Gene Symbol: Kcnn4
Description: potassium calcium-activated channel subfamily N member 4
Alias: KCa3.1, rKCNN4c, rSK4, intermediate conductance calcium-activated potassium channel protein 4, IK1, KCa4, SK4, SKCa 4, SKCa4, intermediate conductance K channel, intermediate-conductance Ca-activated K channel, potassium channel, calcium activated intermediate/small conductance subfamily N alpha, member 4, potassium intermediate/small conductance calcium-activated channel, subfamily N, member 4
Species: rat
Products:     Kcnn4

Top Publications

  1. Singh S, O HARA B, Talukder J, Rajendran V. Aldosterone induces active K? secretion by enhancing mucosal expression of Kcnn4c and Kcnma1 channels in rat distal colon. Am J Physiol Cell Physiol. 2012;302:C1353-60 pubmed publisher
    ..by the mucosal addition of 1) either Ba(2+) (a nonspecific K(+) channel blocker) or charybdotoxin (CTX; a common Kcnn4 and Kcnma1 channel blocker) by 89%; 2) tetraethyl ammonium (TEA) or iberiotoxin (IbTX; a Kcnma1 channel blocker) ..
  2. Hayashi M, Kunii C, Takahata T, Ishikawa T. ATP-dependent regulation of SK4/IK1-like currents in rat submandibular acinar cells: possible role of cAMP-dependent protein kinase. Am J Physiol Cell Physiol. 2004;286:C635-46 pubmed
    ..those of whole cell currents recorded from human embryonic kidney-293 cells heterologously expressing rat SK4/IK1 (rSK4/IK1) cloned from RSA cells...
  3. Nanda Kumar N, Singh S, Rajendran V. Mucosal potassium efflux mediated via Kcnn4 channels provides the driving force for electrogenic anion secretion in colon. Am J Physiol Gastrointest Liver Physiol. 2010;299:G707-14 pubmed publisher
    Intermediate conductance K(+) (Kcnn4) channels are present in both mucosal and serosal membranes of colon. However, only serosal Kcnn4 channels have been shown to be essential for agonist-induced (cAMP and Ca(2+)) anion secretion...
  4. Adelman J, Maylie J, Sah P. Small-conductance Ca2+-activated K+ channels: form and function. Annu Rev Physiol. 2012;74:245-69 pubmed publisher
    ..In this review we discuss the molecular and functional properties of SK channels and their physiological roles in central neurons. ..
  5. Joiner W, Basavappa S, Vidyasagar S, Nehrke K, Krishnan S, Binder H, et al. Active K+ secretion through multiple KCa-type channels and regulation by IKCa channels in rat proximal colon. Am J Physiol Gastrointest Liver Physiol. 2003;285:G185-96 pubmed
    ..blot analysis of rat proximal colon revealed the presence of transcripts encoding rSK2 [small conductance (SK)], rSK4 [intermediate conductance (IK)], and rSlo [large conductance (BK)] Ca2+-activated K+ channels...
  6. 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
  7. Barmeyer C, Rahner C, Yang Y, SIGWORTH F, Binder H, Rajendran V. Cloning and identification of tissue-specific expression of KCNN4 splice variants in rat colon. Am J Physiol Cell Physiol. 2010;299:C251-63 pubmed publisher
    b>KCNN4 channels that provide the driving force for cAMP- and Ca(2+)-induced anion secretion are present in both apical and basolateral membranes of the mammalian colon. However, only a single KCNN4 has been cloned...
  8. Kaushal V, Koeberle P, Wang Y, Schlichter L. The Ca2+-activated K+ channel KCNN4/KCa3.1 contributes to microglia activation and nitric oxide-dependent neurodegeneration. J Neurosci. 2007;27:234-44 pubmed
    ..We present evidence that the small-conductance Ca2+/calmodulin-activated K+ channel KCNN4/ KCa3.1/SK4/IK1 is highly expressed in rat microglia and is a potential therapeutic target for acute brain damage...
  9. Srivastava S, Zhdanova O, Di L, Li Z, Albaqumi M, Wulff H, et al. Protein histidine phosphatase 1 negatively regulates CD4 T cells by inhibiting the K+ channel KCa3.1. Proc Natl Acad Sci U S A. 2008;105:14442-6 pubmed publisher

More Information


  1. Girault A, Chebli J, Privé A, Trinh N, Maillé E, Grygorczyk R, et al. Complementary roles of KCa3.1 channels and β1-integrin during alveolar epithelial repair. Respir Res. 2015;16:100 pubmed publisher
    ..Taken together, our data demonstrate for the first time complementary roles of KCa3.1 and TRPC4 channels with extracellular matrix and β1-integrin in the regulation of alveolar repair processes. ..
  2. Barfod E, Moore A, Roe M, Lidofsky S. Ca2+-activated IK1 channels associate with lipid rafts upon cell swelling and mediate volume recovery. J Biol Chem. 2007;282:8984-93 pubmed
    ..We isolated from rat liver and HTC cells a cDNA with sequence identity to the coding region of IK1. Swelling-activated currents were inhibited by transfection with a dominant interfering IK1 mutant...
  3. Kloza M, Baranowska Kuczko M, Malinowska B, Karpińska O, Harasim Symbor E, Kasacka I, et al. The influence of DOCA-salt hypertension and chronic administration of the FAAH inhibitor URB597 on KCa2.3/KCa3.1-EDH-type relaxation in rat small mesenteric arteries. Vascul Pharmacol. 2017;99:65-73 pubmed publisher
    ..1. Furthermore, KCa3.1 played a key role in the EDH-type dilator response of sMAs in normo- and hypertension. The hypotensive effect of URB597 is independent of KCa2.3/KCa3.1-EDH-type relaxation. ..
  4. Zhu J, Jia R, Xu L, Wu J, Wang Z, Wang S, et al. Reduced expression of SK3 and IK1 channel proteins in the cavernous tissue of diabetic rats. Asian J Androl. 2010;12:599-604 pubmed publisher
    The small (SK3) and intermediate (IK1) conductance calcium-activated potassium channels could have key roles in the endothelium-dependent hyperpolarization factor pathway, which is believed to contribute to normal penile erection ..
  5. Dora K, Gallagher N, McNeish A, Garland C. Modulation of endothelial cell KCa3.1 channels during endothelium-derived hyperpolarizing factor signaling in mesenteric resistance arteries. Circ Res. 2008;102:1247-55 pubmed publisher
    ..3 hyperpolarization appears mainly to affect relaxation through myoendothelial gap junctions. Overall, these data suggest that K(+) and myoendothelial coupling evoke EDHF-mediated relaxation through distinct, definable pathways. ..
  6. Su X, Zhang H, Yu W, Wang S, Zhu W. Role of KCa3.1 channels in proliferation and migration of vascular smooth muscle cells by diabetic rat serum. Chin J Physiol. 2013;56:155-62 pubmed
    ..1 channels blocker TRAM-34. In conclusion, serum from diabetic rats increases the expression of K(Ca)3.1 channels and promotes proliferation and migration of VSMCs to possibly participate in vascular remodeling in diabetes. ..
  7. Guo S, Shen Y, He G, Wang T, Xu D, Wen F. Involvement of Ca2+-activated K+ channel 3.1 in hypoxia-induced pulmonary arterial hypertension and therapeutic effects of TRAM-34 in rats. Biosci Rep. 2017;37: pubmed publisher
    ..Kca3.1 may play a role in the development of PAH by activating ERK/p38 MAP kinase signaling, which may then contribute to hypoxia-induced pulmonary vascular remodeling. TRAM-34 may protect against hypoxia-induced PAH. ..
  8. Mauler F, Hinz V, Horváth E, Schuhmacher J, Hofmann H, Wirtz S, et al. Selective intermediate-/small-conductance calcium-activated potassium channel (KCNN4) blockers are potent and effective therapeutics in experimental brain oedema and traumatic brain injury caused by acute subdural haematoma. Eur J Neurosci. 2004;20:1761-8 pubmed
    ..to characterize their pharmacological properties on KCNN4 channels (intermediate/small conductance calcium-activated potassium channel, subfamily N, member 4) in vitro as ..
  9. Xu X, Xia J, Yang X, Huang X, Gao D, Lian J, et al. Intermediate-conductance Ca(2+) -activated potassium and volume-sensitive chloride channels in endothelial progenitor cells from rat bone marrow mononuclear cells. Acta Physiol (Oxf). 2012;205:302-13 pubmed publisher
    ..The corresponding ion channel genes and proteins, KCNN4 for I(kca) and Clcn3 for I(cl) , were confirmed by RT-PCR and western immunoblot analysis of BMEPCs...
  10. 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. ..
  11. Basalingappa K, Rajendran V, Wonderlin W. Characteristics of Kcnn4 channels in the apical membranes of an intestinal epithelial cell line. Am J Physiol Gastrointest Liver Physiol. 2011;301:G905-11 pubmed publisher
    Intermediate-conductance K(+) (Kcnn4) channels in the apical and basolateral membranes of epithelial cells play important roles in agonist-induced fluid secretion in intestine and colon...
  12. 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...
  13. O HARA B, Alvarez de la Rosa D, Rajendran V. Multiple mineralocorticoid response elements localized in different introns regulate intermediate conductance K+ (Kcnn4) channel expression in the rat distal colon. PLoS ONE. 2014;9:e98695 pubmed publisher
    An elevated plasma aldosterone and an increased expression of the intermediate conductance K(+) (IK/Kcnn4) channels are linked in colon...
  14. Ayabe T, Wulff H, Darmoul D, Cahalan M, Chandy K, Ouellette A. Modulation of mouse Paneth cell alpha-defensin secretion by mIKCa1, a Ca2+-activated, intermediate conductance potassium channel. J Biol Chem. 2002;277:3793-800 pubmed
    ..These results demonstrate that mIKCa1 is modulator of Paneth cell alpha-defensin secretion and disclose an involvement in mucosal defense of the intestinal epithelium against ingested bacterial pathogens. ..
  15. Chen Y, Wallace B, Yuen N, Jenkins D, Wulff H, O Donnell M. Blood-brain barrier KCa3.1 channels: evidence for a role in brain Na uptake and edema in ischemic stroke. Stroke. 2015;46:237-44 pubmed publisher
    ..BBB endothelial cells exhibit KCa3.1 protein and activity and pharmacological blockade of KCa3.1 seems to provide an effective therapeutic approach for reducing cerebral edema formation in the first 3 hours of ischemic stroke. ..
  16. Liu C, Liu E, Luo T, Zhang W, He R. Opening of the inward rectifier potassium channel alleviates maladaptive tissue repair following myocardial infarction. Acta Biochim Biophys Sin (Shanghai). 2016;48:687-95 pubmed publisher
    Activation of the inward rectifier potassium current (IK1) channel has been reported to be associated with suppression of ventricular arrhythmias...
  17. Simonet S, Isabelle M, Bousquenaud M, Clavreul N, Feletou M, Vayssettes Courchay C, et al. KCa 3.1 channels maintain endothelium-dependent vasodilatation in isolated perfused kidneys of spontaneously hypertensive rats after chronic inhibition of NOS. Br J Pharmacol. 2012;167:854-67 pubmed publisher
    ..1 channels, contributed to the mechanism of endothelium-dependent vasodilatation. In kidneys from L-NAME-treated SHR, up-regulation of this pathway fully compensated for the decrease in NO availability. ..
  18. Halling D, Kenrick S, Riggs A, Aldrich R. Calcium-dependent stoichiometries of the KCa2.2 (SK) intracellular domain/calmodulin complex in solution. J Gen Physiol. 2014;143:231-52 pubmed publisher
    ..These results suggest that complexes with stoichiometries other than 2SKp/2CaM are important in gating. ..
  19. Ferreira R, Schlichter L. 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. 2013;8:e62345 pubmed publisher
    ..We previously found that SK3 (KCa2.3) and KCa3.1 (SK4/IK1) are expressed in rat microglia and contribute to LPS-mediated activation and neurotoxicity...
  20. Yarova P, Smirnov S, Dora K, Garland C. ??-Adrenoceptor stimulation suppresses endothelial IK(Ca)-channel hyperpolarization and associated dilatation in resistance arteries. Br J Pharmacol. 2013;169:875-86 pubmed publisher
    ..This effect appears to reflect inhibition of endothelial IK(Ca) channels and may be one consequence of raised circulating catecholamines. ..
  21. 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. ..
  22. Turner R, Asmara H, Engbers J, Miclat J, Rizwan A, Sahu G, et al. Assessing the role of IKCa channels in generating the sAHP of CA1 hippocampal pyramidal cells. Channels (Austin). 2016;10:313-9 pubmed publisher
    ..Together the data firmly establish IKCa channel expression in CA1 neurons and clarify methodological requirements to obtain a block of IKCa channel activity through internal application of TRAM-34. ..
  23. 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
    ..By homology cloning the SK of the rat colon (rSK4) was identified. This protein has a high homology to hSK4 and mouse IK1...
  24. Forsythe P, Wang B, Khambati I, Kunze W. Systemic effects of ingested Lactobacillus rhamnosus: inhibition of mast cell membrane potassium (IKCa) current and degranulation. PLoS ONE. 2012;7:e41234 pubmed publisher
    ..Thus the systemic effects of certain candidate probiotics may include mast cell stabilization and such actions could contribute to the beneficial effect of these organisms in allergic and other inflammatory disorders. ..
  25. Zhao L, Su X, Wang Y, Li G, Deng X. KCa3.1 channels mediate the increase of cell migration and proliferation by advanced glycation endproducts in cultured rat vascular smooth muscle cells. Lab Invest. 2013;93:159-67 pubmed publisher
    ..1 channels in rat VMSCs, and the intracellular signals ERK1/2, P38-MAPK and PI3K are involved in the regulation of K(Ca)3.1 channel expression. ..
  26. Su X, Wang Y, Zhang W, Zhao L, Li G, Deng X. Insulin-mediated upregulation of K(Ca)3.1 channels promotes cell migration and proliferation in rat vascular smooth muscle. J Mol Cell Cardiol. 2011;51:51-7 pubmed publisher
    ..1 channels by stimulating ERK1/2 phosphorylation thereby promoting migration and proliferation of VSMCs, which likely play at least a partial role in the development of vasculopathy in type-2 diabetes. ..
  27. Neylon C, Lang R, Fu Y, Bobik A, Reinhart P. Molecular cloning and characterization of the intermediate-conductance Ca(2+)-activated K(+) channel in vascular smooth muscle: relationship between K(Ca) channel diversity and smooth muscle cell function. Circ Res. 1999;85:e33-43 pubmed
    ..The differential expression of these K(Ca) channels in functionally distinct smooth muscle cell types suggests that K(Ca) channels play a role in defining the physiological properties of vascular smooth muscle. ..
  28. Zundler S, Caioni M, Müller M, Strauch U, Kunst C, Woelfel G. K+ Channel Inhibition Differentially Regulates Migration of Intestinal Epithelial Cells in Inflamed vs. Non-Inflamed Conditions in a PI3K/Akt-Mediated Manner. PLoS ONE. 2016;11:e0147736 pubmed publisher
    ..Furthermore, mRNA-levels of the potassium channel KCNN4 were determined in IEC from patients suffering from inflammatory bowel diseases (IBD)...
  29. Niehof M, Borlak J. RSK4 and PAK5 are novel candidate genes in diabetic rat kidney and brain. Mol Pharmacol. 2005;67:604-11 pubmed
    ..In multiple ChIP assays, ribosomal S6 kinase 4 (RSK4) and p21-activated kinase 5 (PAK5) were confirmed, and in vitro binding of HNF4alpha was evidenced by ..
  30. Glaser N, Little C, Lo W, Cohen M, Tancredi D, Wulff H, et al. Treatment with the KCa3.1 inhibitor TRAM-34 during diabetic ketoacidosis reduces inflammatory changes in the brain. Pediatr Diabetes. 2017;18:356-366 pubmed publisher
    ..Inhibiting KCa3.1 activity with TRAM-34 during DKA treatment decreases microglial activation and reduces reactive astrogliosis, suggesting a decreased inflammatory response. ..
  31. Mongan L, Hill M, Chen M, Tate S, Collins S, Buckby L, et al. The distribution of small and intermediate conductance calcium-activated potassium channels in the rat sensory nervous system. Neuroscience. 2005;131:161-75 pubmed
    ..We show that SK1, SK2, SK3 and IK1 are all expressed in DRG and spinal cord...
  32. Zhao L, Zhang W, Wang L, Li G, Deng X. Advanced glycation end products promote proliferation of cardiac fibroblasts by upregulation of KCa3.1 channels. Pflugers Arch. 2012;464:613-21 pubmed publisher
    ..1 channels in a RAGE-dependent manner and promote cardiac fibroblast proliferation and collagen production, which is mediated by phosphorylation of ERK1/2, p38-MAPK, and PI3K/Akt signals. ..
  33. Hayashi M, Wang J, Hede S, Novak I. An intermediate-conductance Ca2+-activated K+ channel is important for secretion in pancreatic duct cells. Am J Physiol Cell Physiol. 2012;303:C151-9 pubmed publisher
    ..RT-PCR analysis revealed mRNAs for KCNQ1, KCNH2, KCNH5, KCNT1, and KCNT2, as well as KCNN4 coding for the following channels: KVLQT1; HERG; EAG2; Slack; Slick; and an intermediate-conductance Ca(2+)-..
  34. Kang H, Kerloc h A, Rotival M, Xu X, Zhang Q, D Souza Z, et al. Kcnn4 is a regulator of macrophage multinucleation in bone homeostasis and inflammatory disease. Cell Rep. 2014;8:1210-24 pubmed publisher
    ..We identify a trans-regulated gene network associated with macrophage multinucleation and Kcnn4 as being the most significantly trans-regulated gene in the network and induced at the onset of fusion...
  35. Freise C, Heldwein S, Erben U, Hoyer J, Köhler R, Jöhrens K, et al. K⁺-channel inhibition reduces portal perfusion pressure in fibrotic rats and fibrosis associated characteristics of hepatic stellate cells. Liver Int. 2015;35:1244-52 pubmed publisher
    ..Inhibition of KCa3.1 with TRAM-34 downregulates fibrosis-associated gene expression in vitro, and reduces portal perfusion pressure in vivo. Thus, KCa3.1 may represent novel targets for the treatment of liver fibrosis. ..
  36. Dutta A, Khimji A, Sathe M, Kresge C, Parameswara V, Esser V, et al. Identification and functional characterization of the intermediate-conductance Ca(2+)-activated K(+) channel (IK-1) in biliary epithelium. Am J Physiol Gastrointest Liver Physiol. 2009;297:G1009-18 pubmed
    ..Together these studies demonstrate that IK channels are present in biliary epithelial cells and contribute to ATP-stimulated secretion through a P2Y-IP3 receptor pathway...
  37. 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...
  38. Wang Y, Zhao L, Su X, Yu W, Deng X. [Ca(2+)-activated K(+) channel switching in smooth muscle participates in atherosclerosis development in diabetic rats]. Nan Fang Yi Ke Da Xue Xue Bao. 2014;34:188-92 pubmed
    ..1 channels was obviously enhanced in the middle layer of the aorta in the diabetic rats. KCa channel switching in smooth muscles may play a role in the development of atherosclerosis in diabetic rats. ..
  39. Rapetti Mauss R, Lacoste C, Picard V, Guitton C, Lombard E, Loosveld M, et al. A mutation in the Gardos channel is associated with hereditary xerocytosis. Blood. 2015;126:1273-80 pubmed publisher
    ..The identification of a KCNN4 mutation associated with chronic hemolysis constitutes the first report of a human disease caused by a defect of ..