intermediate conductance calcium activated potassium channels


Summary: A major class of calcium-activated potassium channels that were originally discovered in ERYTHROCYTES. They are found primarily in non-excitable CELLS and set up electrical gradients for PASSIVE ION TRANSPORT.

Top Publications

  1. Sciaccaluga M, Fioretti B, Catacuzzeno L, Pagani F, Bertollini C, Rosito M, et al. CXCL12-induced glioblastoma cell migration requires intermediate conductance Ca2+-activated K+ channel activity. Am J Physiol Cell Physiol. 2010;299:C175-84 pubmed publisher
    ..All together these findings suggest that the efficacy of glioblastoma invasiveness might be related to an array of nonoverlapping mechanisms activated by different chemotactic agents. ..
  2. Feng J, Liu Y, Khabbaz K, Sodha N, Osipov R, Hagberg R, et al. Large conductance calcium-activated potassium channels contribute to the reduced myogenic tone of peripheral microvasculature after cardiopulmonary bypass. J Surg Res. 2009;157:123-8 pubmed publisher
    ..CPB-associated decrease in peripheral myogenic reactivity is likely due to activation of BK(Ca), but not IK(Ca) or SK(Ca). CPB may increase BK(Ca) activity without increasing BK polypeptide level. ..
  3. Dalsgaard T, Kroigaard C, Misfeldt M, Bek T, Simonsen U. Openers of small conductance calcium-activated potassium channels selectively enhance NO-mediated bradykinin vasodilatation in porcine retinal arterioles. Br J Pharmacol. 2010;160:1496-508 pubmed publisher
    ..These results imply that opening SK(Ca) channels improves endothelium-dependent relaxation and makes this channel a potential target for treatments aimed at restoring retinal blood flow. ..
  4. Hilgers R, Janssen G, Fazzi G, De Mey J. Twenty-four-hour exposure to altered blood flow modifies endothelial Ca2+-activated K+ channels in rat mesenteric arteries. J Pharmacol Exp Ther. 2010;333:210-7 pubmed publisher
    ..Reduction of blood flow selectively blunts EDHF relaxation in resistance arteries through inhibition of the function of K(Ca) channels. An increase in blood flow leads to a more prominent role of IK1 channels in this relaxation. ..
  5. Smeda J, McGuire J, Daneshtalab N. Protease-activated receptor 2 and bradykinin-mediated vasodilation in the cerebral arteries of stroke-prone rats. Peptides. 2010;31:227-37 pubmed publisher
    ..Despite the presence of vascular injury, edema, inflammation and the loss of endothelium-dependent bradykinin vasodilation we found no evidence that PAR(2) expression or vascular function was altered in MCA after stroke. ..
  6. Makhro A, Wang J, Vogel J, Boldyrev A, Gassmann M, Kaestner L, et al. Functional NMDA receptors in rat erythrocytes. Am J Physiol Cell Physiol. 2010;298:C1315-25 pubmed publisher
    ..Moreover, receptor hyperactivation may contribute to an increased incidence of thrombosis during hyperhomocysteinemia. ..
  7. Dalsgaard T, Kroigaard C, Simonsen U. Calcium-activated potassium channels - a therapeutic target for modulating nitric oxide in cardiovascular disease?. Expert Opin Ther Targets. 2010;14:825-37 pubmed publisher
    ..Opening of SK and IK channels can increase both EDHF and NO-mediated vasodilatation. Therefore, openers of SK and IK channels may have the potential of improving endothelial cell function in cardiovascular disease. ..
  8. 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
    ..These observations indicate that mucosal Kcnn4 channels are capable of driving agonist-induced anion secretion mediated via CFTR and CaCC and likely contribute to stool K(+) losses that accompany diarrheal illnesses. ..
  9. Pegoraro S, Lang M, Dreker T, Kraus J, Hamm S, Meere C, et al. Inhibitors of potassium channels KV1.3 and IK-1 as immunosuppressants. Bioorg Med Chem Lett. 2009;19:2299-304 pubmed publisher
    ..These compounds display inhibitory effects on T-cell and/or keratinocyte proliferation and immunosuppressant activity within a DTH animal model. ..

More Information


  1. Cipolla M, Smith J, Kohlmeyer M, Godfrey J. SKCa and IKCa Channels, myogenic tone, and vasodilator responses in middle cerebral arteries and parenchymal arterioles: effect of ischemia and reperfusion. Stroke. 2009;40:1451-7 pubmed publisher
    ..The preservation of EDHF responsiveness of PA after ischemia and reperfusion suggests an important role for this vasodilator under conditions when NOS is inhibited. ..
  2. 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. ..
  3. Romanenko V, Roser K, Melvin J, Begenisich T. The role of cell cholesterol and the cytoskeleton in the interaction between IK1 and maxi-K channels. Am J Physiol Cell Physiol. 2009;296:C878-88 pubmed publisher
  4. Faouzi M, Chopin V, Ahidouch A, Ouadid Ahidouch H. Intermediate Ca2+-sensitive K+ channels are necessary for prolactin-induced proliferation in breast cancer cells. J Membr Biol. 2010;234:47-56 pubmed publisher
    ..Taken together, our results demonstrate that PRL plays a role in breast cancer cell proliferation by increasing hIKCa1 activity through the JAK2 signaling pathway. ..
  5. 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
    ..05). Diabetes inhibits mRNA and protein expression of both SK3 and IK1 in the cavernous tissue of diabetic rats. This could play a key role in the development of erectile dysfunction in diabetic rats. ..
  6. Simms L, Doecke J, Roberts R, Fowler E, Zhao Z, McGuckin M, et al. KCNN4 gene variant is associated with ileal Crohn's Disease in the Australian and New Zealand population. Am J Gastroenterol. 2010;105:2209-17 pubmed publisher
    ..Our data implicate the role of KCNN4 in ileal CD. The dual roles of KCNN4 in Paneth cell secretion and T-cell activation and also its nature as a potassium channel make it an important and practical therapeutic target. ..
  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
    ..6 +/- 0.1 and 7.8 +/- 0.4 muM, respectively. We conclude that apical and basolateral KCNN4 K(+) channels that regulate K(+) and anion secretion are encoded by distinct isoforms in colonic epithelial cells. ..
  8. Yamaguchi M, Nakayama T, Fu Z, Naganuma T, Sato N, Soma M, et al. Relationship between haplotypes of KCNN4 gene and susceptibility to human vascular diseases in Japanese. Med Sci Monit. 2009;15:CR389-97 pubmed
    ..6%). The specific SNPs and haplotypes in the KCNN4 gene showed significant differences between MI and control patients. These results indicate that these polymorphisms and haplotypes could be genetic markers for MI. ..
  9. Zhang Z, Rosenhouse Dantsker A, Tang Q, Noskov S, Logothetis D. The RCK2 domain uses a coordination site present in Kir channels to confer sodium sensitivity to Slo2.2 channels. J Neurosci. 2010;30:7554-62 pubmed publisher
    ..The localization of an Na(+) sensor within the RCK2 domain of Slo2.2 further supports the role of RCK (regulators of conductance of K(+)) domains of Slo channels in coupling ion sensing to channel gating. ..
  10. Fioretti B, Catacuzzeno L, Sforna L, Aiello F, Pagani F, Ragozzino D, et al. Histamine hyperpolarizes human glioblastoma cells by activating the intermediate-conductance Ca2+-activated K+ channel. Am J Physiol Cell Physiol. 2009;297:C102-10 pubmed publisher
    ..3 microM, at -40 mV. Notably in no instance was the BK(Ca) channel activated by histamine under physiological conditions. The most parsimonious explanation based on the different K(D(Ca)) for the two K(Ca) channels is provided. ..
  11. Haren N, Khorsi H, Faouzi M, Ahidouch A, Sevestre H, Ouadid Ahidouch H. Intermediate conductance Ca2+ activated K+ channels are expressed and functional in breast adenocarcinomas: correlation with tumour grade and metastasis status. Histol Histopathol. 2010;25:1247-55 pubmed publisher
    ..1-mediated currents in these cells. In conclusion, these data suggest that hKCa3.1 might contribute to breast tumour-progression and can serve as a useful prognostic marker for breast cancer. ..
  12. Millership J, Heard C, Fearon I, Bruce J. Differential regulation of calcium-activated potassium channels by dynamic intracellular calcium signals. J Membr Biol. 2010;235:191-210 pubmed publisher
    ..These phenomena may be important for encoding stimulus-response coupling in various cell types. ..
  13. 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. ..
  14. de Wit C, Griffith T. Connexins and gap junctions in the EDHF phenomenon and conducted vasomotor responses. Pflugers Arch. 2010;459:897-914 pubmed publisher
    ..The present review will focus on the complex interactions between the diverse cellular signaling mechanisms that contribute to these phenomena. ..
  15. Brøndum E, Kold Petersen H, Simonsen U, Aalkjaer C. NS309 restores EDHF-type relaxation in mesenteric small arteries from type 2 diabetic ZDF rats. Br J Pharmacol. 2010;159:154-65 pubmed publisher
    ..These results may have clinical implications for the treatment of endothelial dysfunction in overweight type 2 diabetic patients. ..
  16. Lallet Daher H, Roudbaraki M, Bavencoffe A, Mariot P, Gackiere F, Bidaux G, et al. Intermediate-conductance Ca2+-activated K+ channels (IKCa1) regulate human prostate cancer cell proliferation through a close control of calcium entry. Oncogene. 2009;28:1792-806 pubmed publisher
    ..Thus, the overexpression of the IK(Ca1) channel is likely to promote carcinogenesis in human prostate tissue. ..
  17. Köhler R, Ruth P. Endothelial dysfunction and blood pressure alterations in K+-channel transgenic mice. Pflugers Arch. 2010;459:969-76 pubmed publisher
    ..These alterations strengthen the perspective that vascular K(+) channels are potential pharmacologic targets for improvement of vasodilator functions in cardiovascular pathologies. ..
  18. Köhler R, Kaistha B, Wulff H. Vascular KCa-channels as therapeutic targets in hypertension and restenosis disease. Expert Opin Ther Targets. 2010;14:143-55 pubmed publisher
    ..Additional efforts are required to optimize these compounds and to validate them as cardiovascular-protective drugs. ..
  19. 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...
  20. Han D, Nie H, Gu X, Nayak R, Su X, Fu J, et al. K+ channel openers restore verapamil-inhibited lung fluid resolution and transepithelial ion transport. Respir Res. 2010;11:65 pubmed publisher
    ..Our observations demonstrate that K+ channel openers are capable of rescuing reduced vectorial Na+ transport across lung epithelial cells with impaired Ca2+ signal. ..
  21. 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
    ..This provides a novel strategy for the enrichment of cardiomyocytes and in particular, the generation of a specific subtype of cardiomyocytes, pacemaker-like cells, without genetic modification. ..
  22. Emter C, Bowles D. Store-operated Ca(2+) entry is not essential for PDGF-BB induced phenotype modulation in rat aortic smooth muscle. Cell Calcium. 2010;48:10-8 pubmed publisher
    ..Our results indicate SOCE is not required for PDGF-BB induced phenotype modulation in rat aortic SMCs. Rather, we implicate a novel BEL-sensitive mechanism which regulates both SOCE and phenotype modulation, independently. ..
  23. Chadha P, Haddock R, Howitt L, Morris M, Murphy T, Grayson T, et al. Obesity up-regulates intermediate conductance calcium-activated potassium channels and myoendothelial gap junctions to maintain endothelial vasodilator function. J Pharmacol Exp Ther. 2010;335:284-93 pubmed publisher
    ..Plasticity of myoendothelial coupling mechanisms represents a significant potential target for therapeutic intervention. ..
  24. Weston A, Porter E, Harno E, Edwards G. Impairment of endothelial SK(Ca) channels and of downstream hyperpolarizing pathways in mesenteric arteries from spontaneously hypertensive rats. Br J Pharmacol. 2010;160:836-43 pubmed publisher
    ..The aim of the present study was to determine whether this reflects down-regulation of endothelial K(+) channels or their associated pathways...
  25. 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. ..
  26. Köhler R. Single-nucleotide polymorphisms in vascular Ca2+-activated K+-channel genes and cardiovascular disease. Pflugers Arch. 2010;460:343-51 pubmed publisher
    ..These findings from sequence analysis of human KCa genes, and epidemiological studies thus provide evidence that genetic variations and mutations in KCa channel genes contribute to human cardiovascular disease. ..
  27. Dalsgaard T, Kroigaard C, Bek T, Simonsen U. Role of calcium-activated potassium channels with small conductance in bradykinin-induced vasodilation of porcine retinal arterioles. Invest Ophthalmol Vis Sci. 2009;50:3819-25 pubmed publisher
    ..Moreover, these findings suggest that SK(Ca) channels contribute to NO-mediated relaxation induced by bradykinin and NS309 and, hence, may play an important role in retinal arterial endothelial function. ..
  28. Traut M, Berg D, Berg U, Mayerhofer A, Kunz L. Identification and characterization of Ca2+-activated K+ channels in granulosa cells of the human ovary. Reprod Biol Endocrinol. 2009;7:28 pubmed publisher
    ..g. acetylcholine, ATP, dopamine). The knowledge of ovarian K(Ca) channel properties and functions should help to understand the link between endocrine and paracrine/autocrine control in the human ovary. ..
  29. De Marchi U, Sassi N, Fioretti B, Catacuzzeno L, Cereghetti G, Szabo I, et al. Intermediate conductance Ca2+-activated potassium channel (KCa3.1) in the inner mitochondrial membrane of human colon cancer cells. Cell Calcium. 2009;45:509-16 pubmed publisher
    ..Moderate increases of mitochondrial matrix [Ca(2+)] will cause mtK(Ca)3.1 opening, thus linking inner membrane K(+) permeability and transmembrane potential to Ca(2+) signalling. ..
  30. Liu Y, Sellke E, Feng J, Clements R, Sodha N, Khabbaz K, et al. Calcium-activated potassium channels contribute to human skeletal muscle microvascular endothelial dysfunction related to cardiopulmonary bypass. Surgery. 2008;144:239-44 pubmed publisher
    ..CPB-associated microvascular dysfunction likely arises in part from impaired function of endothelial SK and IK channels in the peripheral microvasculature. ..
  31. Chimote A, Adragna N, Lauf P. Ion transport in a human lens epithelial cell line exposed to hyposmotic and apoptotic stress. J Cell Physiol. 2010;223:110-22 pubmed publisher
  32. Yun J, Park H, Ko J, Lee W, Kim T, Shin J, et al. Expression of Ca2+ -activated K+ channels in human dermal fibroblasts and their roles in apoptosis. Skin Pharmacol Physiol. 2010;23:91-104 pubmed publisher
  33. Balut C, Gao Y, Murray S, Thibodeau P, Devor D. ESCRT-dependent targeting of plasma membrane localized KCa3.1 to the lysosomes. Am J Physiol Cell Physiol. 2010;299:C1015-27 pubmed publisher
    ..1 degradation, compared with wild-type controls. These results are the first to demonstrate that plasma membrane-associated KCa3.1 is targeted for lysosomal degradation via a Rab7 and ESCRT-dependent pathway. ..
  34. Chantome A, Girault A, Potier M, Collin C, Vaudin P, Pages J, et al. KCa2.3 channel-dependent hyperpolarization increases melanoma cell motility. Exp Cell Res. 2009;315:3620-30 pubmed publisher
    ..3 channel. Our findings reveal a previously unknown function of the KCa2.3 channel, and suggest that the KCa2.3 channel might be the only member of the Ca(2+)-activated K(+) channel family involved in melanoma cell motility pathways. ..
  35. 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...
  36. Gomez R, Caballero R, Barana A, Amorós I, Calvo E, Lopez J, et al. Nitric oxide increases cardiac IK1 by nitrosylation of cysteine 76 of Kir2.1 channels. Circ Res. 2009;105:383-92 pubmed publisher
    ..1 channels in human atrial samples as demonstrated by a biotin-switch assay, followed by Western blot. The results demonstrated that, under physiological conditions, NO regulates human cardiac I(K1) through a redox-related process. ..
  37. Srivastava S, Di L, Zhdanova O, Li Z, Vardhana S, Wan Q, et al. The class II phosphatidylinositol 3 kinase C2beta is required for the activation of the K+ channel KCa3.1 and CD4 T-cells. Mol Biol Cell. 2009;20:3783-91 pubmed publisher
    ..This is the first demonstration that a class II PI3K plays a critical role in T-cell activation. ..
  38. Dora K. Coordination of vasomotor responses by the endothelium. Circ J. 2010;74:226-32 pubmed
    ..This review will focus on the cross-talk between ECs and SMCs that coordinates the spread of hyperpolarization and thus modulates smooth muscle tone. ..
  39. Abdullaev I, Rudkouskaya A, Mongin A, Kuo Y. Calcium-activated potassium channels BK and IK1 are functionally expressed in human gliomas but do not regulate cell proliferation. PLoS ONE. 2010;5:e12304 pubmed publisher
    ..Taken together, these results suggest that Ca(2+)-activated K(+) channels do not play a critical role in proliferation of glioma cells and that the effects of pharmacological inhibitors occur through their off-target actions. ..
  40. Dufer M, Gier B, Wolpers D, Krippeit Drews P, Ruth P, Drews G. Enhanced glucose tolerance by SK4 channel inhibition in pancreatic beta-cells. Diabetes. 2009;58:1835-43 pubmed publisher
    ..Therefore, pharmacologic modulation of these channels might provide an interesting approach for the development of novel insulinotropic drugs. ..
  41. Barro Soria R, Aldehni F, Almaca J, Witzgall R, Schreiber R, Kunzelmann K. ER-localized bestrophin 1 activates Ca2+-dependent ion channels TMEM16A and SK4 possibly by acting as a counterion channel. Pflugers Arch. 2010;459:485-97 pubmed publisher
    ..Thus, bestrophin 1 regulates compartmentalized Ca(2+) signaling that plays an essential role in Best macular dystrophy, inflammatory diseases such as cystic fibrosis, as well as proliferation. ..
  42. Durpes M, Nebor D, du Mesnil P, Mougenel D, Decastel M, Elion J, et al. Effect of interleukin-8 and RANTES on the Gardos channel activity in sickle human red blood cells: role of the Duffy antigen receptor for chemokines. Blood Cells Mol Dis. 2010;44:219-23 pubmed publisher
  43. Varga Z, Csepany T, Papp F, Fabian A, Gogolak P, Toth A, et al. Potassium channel expression in human CD4+ regulatory and naïve T cells from healthy subjects and multiple sclerosis patients. Immunol Lett. 2009;124:95-101 pubmed publisher
    ..1 channels was similar in all cell subsets. The observed differences in K(V)1.3 channel expression density may contribute to the varying responses upon antigenic stimulation by these cell types in health and disease. ..
  44. Gao Y, Hanley P, Rinné S, Zuzarte M, Daut J. Calcium-activated K(+) channel (K(Ca)3.1) activity during Ca(2+) store depletion and store-operated Ca(2+) entry in human macrophages. Cell Calcium. 2010;48:19-27 pubmed publisher
    ..1 channel current and hyperpolarization, providing the necessary electrochemical driving force for prolonged Ca(2+) signaling and store repletion. ..
  45. Bradding P, Wulff H. The K+ channels K(Ca)3.1 and K(v)1.3 as novel targets for asthma therapy. Br J Pharmacol. 2009;157:1330-9 pubmed publisher
    ..3 and K(Ca)3.1 in the treatment of asthma. ..
  46. 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. ..
  47. Mitkevich V, Tchurikov N, Zelenikhin P, Petrushanko I, Makarov A, Ilinskaya O. Binase cleaves cellular noncoding RNAs and affects coding mRNAs. FEBS J. 2010;277:186-96 pubmed publisher
    ..In contrast, expression of the proapoptotic genes p53 and hSK4 was increased 1.5-fold and 4.3-fold, respectively. These results show that binase is a regulator of RNA-dependent processes of cell proliferation and apoptosis. ..
  48. Bajwa P, Lee J, Straus D, Lytle C. Activation of PPARgamma by rosiglitazone attenuates intestinal Cl- secretion. Am J Physiol Gastrointest Liver Physiol. 2009;297:G82-9 pubmed publisher
    ..1 channel protein. Our results establish TZD drugs as important modulators of intestinal Cl- secretory function. ..
  49. Sones W, Leblanc N, Greenwood I. Inhibition of vascular calcium-gated chloride currents by blockers of KCa1.1, but not by modulators of KCa2.1 or KCa2.3 channels. Br J Pharmacol. 2009;158:521-31 pubmed publisher
    ..1 blockers also reduce I(ClCa) considerably. However, the pharmacological overlap that exists between CaCCs and K(Ca)1.1 does not extend to the calcium-binding domain or to other calcium-gated K(+) channels. ..