K<sub>Ca</sub>3.1 | Calcium- and sodium-activated potassium channels | IUPHAR Guide to IMMUNOPHARMACOLOGY

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KCa3.1

  Target has curated data in GtoImmuPdb

Target id: 384

Nomenclature: KCa3.1

Family: Calcium- and sodium-activated potassium channels

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

Contents:

Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 1 427 19q13.2 KCNN4 potassium calcium-activated channel subfamily N member 4 22-23,27,29,39
Mouse 6 1 425 7 A3 Kcnn4 potassium intermediate/small conductance calcium-activated channel, subfamily N, member 4 67
Rat 6 1 424 1q21 Kcnn4 potassium calcium-activated channel subfamily N member 4 69
Previous and Unofficial Names
Gardos channel | IKCa1 | Ik1 | KCa4 | intermediate-conductance Ca-activated K channel | SK4 | potassium channel, calcium activated intermediate/small conductance subfamily N alpha, member 4 | potassium intermediate/small conductance calcium-activated channel
Database Links
ChEMBL Target CHEMBL4305 (Hs)
DrugBank Target O15554 (Hs)
Ensembl Gene ENSG00000104783 (Hs), ENSMUSG00000054342 (Mm), ENSRNOG00000019440 (Rn)
Entrez Gene 3783 (Hs), 16534 (Mm), 65206 (Rn)
Human Protein Atlas ENSG00000104783 (Hs)
KEGG Gene hsa:3783 (Hs), mmu:16534 (Mm), rno:65206 (Rn)
OMIM 602754 (Hs)
RefSeq Nucleotide NM_002250 (Hs), NM_008433 (Mm), NM_023021 (Rn)
RefSeq Protein NP_002241 (Hs), NP_032459 (Mm), NP_075410 (Rn)
UniProtKB O15554 (Hs), O89109 (Mm), Q9QYW1 (Rn)
Wikipedia KCNN4 (Hs)
Associated Proteins
Heteromeric Pore-forming Subunits
Name References
Not determined
Auxiliary Subunits
Name References
Not determined
Other Associated Proteins
Name References
calmodulin 17,32
nucleoside diphosphate kinase B (NDPK-B) 14,57-58
Functional Characteristics
IKCa
Ion Selectivity and Conductance
Species:  Human
Rank order:  K+ [11.0 - 40.0 pS] > Rb+ > NH4+ > Cs+
References:  26-27,29
Voltage Dependence Comments
KCa3.1 is voltage independent.

Download all structure-activity data for this target as a CSV file

Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
NS309 Hs Agonist 8.0 pEC50 - -90.0 61,70
⤷ pEC50 8.0 [61,70]
Holding voltage: -90.0 mV
SKA-121 Hs Agonist 7.0 pEC50 - - 11
⤷ pEC50 7.0 (EC50 1.09x10-7 M) [11]
SKA-31 Hs - 6.6 pEC50 - - 53
⤷ pEC50 6.6 [53]
Ca2+ Hs Agonist 6.1 – 7.0 pEC50 - -120.0 – 60.0 26-27,29,39,63
⤷ pEC50 6.1 – 7.0 [26-27,29,39,63]
Holding voltage: -120.0 – 60.0 mV
DC-EBIO Hs Agonist 6.1 pEC50 - -100.0 56
⤷ pEC50 6.1 [56]
Holding voltage: -100.0 mV
EBIO Hs Agonist 4.1 – 4.5 pEC50 - -100.0 – -50.0 46,63,70
⤷ pEC50 4.1 – 4.5 [46,63,70]
Holding voltage: -100.0 – -50.0 mV
chlorzoxazone Hs Agonist 4.0 pEC50 - -100.0 63
⤷ pEC50 4.0 (EC50 1x10-4 M) [63]
Holding voltage: -100.0 mV
riluzole Hs - 5.7 pIC50 - - 53
⤷ pIC50 5.7 [53]
Activator Comments
No species differences described; NS309, DCEBIO, riluzole and EBIO increase the Ca2+ sensitivity of both KCa3.1 and KCa2 channels; see [73-74] for a recent extensive review of KCa3.1 and KCa2 channel pharmacology.
Gating Inhibitor Comments
[1,3-phenylenebis(methylene) bis(3-fluoro-4-hydroxybenzoate) (RA-2) is a negative gating modulator that inhibits KCa3.1 with an IC50 of 17 nM and all three KCa2 channels with similar potency. It right-shifts the Ca2+ activation curve [43]. The inhibitory gating modulator of KCa2 channels NS8593 does not block KCa3.1 [60].
Channel Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
charybdotoxin Hs Inhibition 8.5 pKd - - 23
⤷ pKd 8.5 [23]
TRAM-34 Hs Inhibition 7.6 – 8.0 pKd - - 38,75
⤷ pKd 7.6 – 8.0 [38,75]
charybdotoxin-GLU32 analog Hs Inhibition 7.5 pKd - - 49
⤷ pKd 7.5 [49]
clotrimazole Hs Inhibition 6.4 – 7.6 pKd - - 22,27,39,75
⤷ pKd 6.4 – 7.6 [22,27,39,75]
nitrendipine Hs Inhibition 6.1 pKd - - 75
⤷ pKd 6.1 [75]
maurotoxin Hs Inhibition 9.0 pIC50 - - 8
⤷ pIC50 9.0 [8]
NS6180 Hs Inhibition 9.0 pIC50 - - 62
⤷ pIC50 9.0 [62]
charybdotoxin Hs - 7.6 – 8.7 pIC50 - - 28-29
⤷ pIC50 7.6 – 8.7 (IC50 2.8x10-8 – 2x10-9 M) [28-29]
senicapoc Hs Inhibition 8.0 pIC50 - - 59
⤷ pIC50 8.0 (IC50 1.1x10-8 M) [59]
compound rac-16 [PMID: 15603962] Hs Inhibition 7.9 – 8.0 pIC50 - - 41,65
⤷ pIC50 7.9 – 8.0 [41,65]
nitrendipine Hs Inhibition 7.6 pIC50 - - 28
⤷ pIC50 7.6 [28]
Channel Blocker Comments
Many more blockers have been characterised; see [73-74] for an extensive review of the pharmacology.
Immunopharmacology Comments
KCa3.1 and KV1.3 are the predominant potassium channels involved in regulating the hyperpolarized (negative) membrane potential which is critical for immune cell activation [12,18,40]. KCa3.1 is voltage-independent and is activated by Ca2+ binding to the calmodulin that is always present at the channel's C terminus. In activated T cells, KCa3.1 and KV1.3 localise to the immunological synapse, where interactions with regulatory kinases occurs. In addition to functions in cell cycle progression and cellular proliferation, KCa3.1 channels play an important immunoregulatory role, including participation in pathologic mechanisms that are associated with the inflammatory and proliferative cascades that characterise autoimmune diseases such as rheumatoid arthritis [20,50]. Notably KCa3.1 knockout mice are resistant to experimental collagen‐induced (i.e. autoimmune) arthritis [50]. KCa3.1 is involved in lymphocyte activation, and in the proliferation and migration of T cells, B cells, mast cells, macrophages and fibroblasts. As an inflammation-relevant drug target [71], KCa3.1 modulators are being investigated for potential in the treatment of asthma and fibroproliferative disorders, and for immunosuppressant efficacy [68].
Cell Type Associations
Immuno Cell Type:  T cells
Comment:  KCa3.1 is expressed in CCR7+ naïve and central memory T cells. It is involved in the activation of, and cytokine production by Th1, Th2 and central memory T cells.
References:  18,66,74
Immuno Cell Type:  Mast cells
Comment:  KCa3.1 is expressed by mast cells.
References:  74
Immuno Cell Type:  Macrophages & monocytes
References:  74
Immuno Process Associations
Immuno Process:  Immune regulation
GO Annotations:  Associated to 1 GO processes
GO:0050862 positive regulation of T cell receptor signaling pathway IDA
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 1 GO processes
GO:0050862 positive regulation of T cell receptor signaling pathway IDA
Tissue Distribution
T and B lymphocytes
Species:  Human
Technique:  Northern Blot, electrophysiology and pharmacology
References:  23,26,31,33,72-73
Placenta, lung, pancreas, colon, stomach, prostate, thymus, spleen, lymph node, bone marrow, peripheral blood, but absent from (brain, heart and skeletal muscle)
Species:  Human
Technique:  Northern Blot
References:  23,27,29,39
KCa3.1 has been implicated with the proliferation of and found in cancer cell lines: LNCaP and PC-3 prostate cancer cells, leukemic HL-60 cells, glioblastoma GL-15 cells, MCF-7 breast cancer cells, BxPC-3 and MiaPaCa-2 pancreatic cancer cells, HEC-1A and KLE endometrial cancer cells
Species:  Human
Technique:  Electrophysiology, Pharmacology, RT-PCR
References:  19,30,44-45
Erythrocytes
Species:  Mouse
Technique:  Northern Blot, KCa3.1 knock-out mice
References:  4,67
Proliferating smooth muscle and fibroblasts
Species:  Rat
Technique:  RT-PCR, Electrophysiology, Immunohistochemistry
References:  38,42,47,64,73
Vascular endothelium, lung and colonic endothelium, Paneth cells
Species:  Rat
Technique:  Electrophysiology, Pharmacology, RT-PCR
References:  3,13,15,52,73
Functional Assays
Whole-cell patch-clamp and single channel recordings of KCa3.1
Species:  Human
Tissue:  T and B lymphocytes
Response measured:  KCa3.1 current
References:  23,26,72,75
Whole-cell patch-clamp and single channel recordings of KCa3.1
Species:  Rat
Tissue:  Microglia, proliferating vascular smooth muscle, colonic endothelium
Response measured:  KCa3.1 current
References:  31,33,38,69
Calcium-dependent K+ or Rb+ flux
Species:  Human
Tissue:  Erythrocytes
Response measured:  K+/Rb+ flux, Gardos "effect"
References:  16,21,59
Endothelium-derived hyperpolarizing factor (EDHF) mediated vasodilation can be measured in various arterial preparations from humans, rats, mice or pigs
Species:  Rat
Tissue:  Mesenteric, carotid, cerebral, coronary and renal arteries
Response measured:  Vasodilation
References:  7,15,73
Two electrode voltage-clamp or whole cell patch-clamp recording of heterologously expressed KCa3.1 (varying concentrations of Ca2+ to activate current in patch-electrode)
Species:  Human
Tissue:  HEK 293 cells, CHO cells, COS-7 cells, Xenopus oocytes
Response measured:  KCa3.1 current
References:  8,23,27-29,39,46,49,61,75
Physiological Functions
Volume regulation, calcium-dependent dehydration of sickle cell erythrocytes during sickling process, erythrocyte and lymphocyte volume regulation impaired in KCa3.1-/- mouse
Species:  Human
Tissue:  Erythrocytes (Gardos channel), lymphocytes, osteoblasts
References:  32
Hyperpolarization to facilitate calcium influx during cellular proliferation
Species:  Human
Tissue:  T and B cells, fibroblasts, vascular smooth muscle, vascular endothelial cells (angiogenesis), cancer cell lines
References:  23,25,32,38,42,47,72,75
Involved in fluid and salt transport in secretory epithelia (various species including mouse, rat and rabbit)
Species:  Mouse
Tissue:  Colonic and lung epithelium, colonic crypts, Panth cells
References:  3,13,52,69,73
Endothelium-derived hyperpolarizing factor (EDHF) mediated vasodilation can be measured in various arterial preparations from humans, rats, mice or pigs, KCa3.1-/- mouse shows reduced EDHF response
Species:  Mouse
Tissue:  Mesenteric, carotid, cerebral, coronary and renal arteries
References:  7,15,37,55,73
Oxidative burst
Species:  Rat
Tissue:  Microglia
References:  31,33
Migration
Species:  Human
Tissue:  Macrophages, microglia (rat), vascular smooth muscle (pig)
References:  10,54,64,73
Slow afterhypolarization in CA1 Pyramidal neurons
Species:  Mouse
Tissue:  Brain
References:  34
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Kcnn4tm1.1Jele Kcnn4tm1.1Jele/Kcnn4tm1.1Jele
either: (involves: 129S1/Sv * 129X1/SvJ) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6)		 MGI:1277957  MP:0001663 abnormal digestive system physiology PMID: 16571783 
Kcnn4tm1Rklr Kcnn4tm1Rklr/Kcnn4tm1Rklr
involves: 129S/SvEv * C57BL/6		 MGI:1277957  MP:0003657 abnormal erythrocyte osmotic lysis PMID: 19037656 
Kcnn4tm1Rklr Kcnn4tm1Rklr/Kcnn4tm1Rklr
involves: 129S/SvEv * C57BL/6		 MGI:1277957  MP:0003921 abnormal heart left ventricle morphology PMID: 16873714 
Kcnn4tm1Rklr Kcnn4tm1Rklr/Kcnn4tm1Rklr
involves: 129S/SvEv * C57BL/6		 MGI:1277957  MP:0000266 abnormal heart morphology PMID: 16873714 
Kcnn4tm1Jemn Kcnn4tm1Jemn/Kcnn4tm1Jemn
involves: 129S1/Sv * C57BL/6J		 MGI:1277957  MP:0001545 abnormal hematopoietic system physiology PMID: 15347667 
Kcnn4tm1Rklr Kcnn4tm1Rklr/Kcnn4tm1Rklr
involves: 129S/SvEv * C57BL/6		 MGI:1277957  MP:0009568 abnormal red blood cell deformability PMID: 19037656 
Kcnn4tm1Rklr Kcnn4tm1Rklr/Kcnn4tm1Rklr
involves: 129S/SvEv * C57BL/6		 MGI:1277957  MP:0000230 abnormal systemic arterial blood pressure PMID: 16873714 
Kcnn4tm1Jemn Kcnn4tm1Jemn/Kcnn4tm1Jemn
involves: 129S1/Sv * C57BL/6J		 MGI:1277957  MP:0002444 abnormal T cell physiology PMID: 15347667 
Kcnn4tm1Rklr Kcnn4tm1Rklr/Kcnn4tm1Rklr
involves: 129S/SvEv * C57BL/6		 MGI:1277957  MP:0005591 decreased vasodilation PMID: 16873714 
Kcnn4tm1Rklr Kcnn4tm1Rklr/Kcnn4tm1Rklr
involves: 129S/SvEv * C57BL/6		 MGI:1277957  MP:0000691 enlarged spleen PMID: 19037656 
Kcnn4tm1Rklr Kcnn4tm1Rklr/Kcnn4tm1Rklr
involves: 129S/SvEv * C57BL/6		 MGI:1277957  MP:0002833 increased heart weight PMID: 16873714 
Kcnn4tm1Rklr Kcnn4tm1Rklr/Kcnn4tm1Rklr
involves: 129S/SvEv * C57BL/6		 MGI:1277957  MP:0002608 increased hematocrit PMID: 19037656 
Kcnn4tm1Rklr Kcnn4tm1Rklr/Kcnn4tm1Rklr
involves: 129S/SvEv * C57BL/6		 MGI:1277957  MP:0008850 increased hemoglobin concentration distribution width PMID: 19037656 
Kcnn4tm1Rklr Kcnn4tm1Rklr/Kcnn4tm1Rklr
involves: 129S/SvEv * C57BL/6		 MGI:1277957  MP:0002590 increased mean corpuscular volume PMID: 19037656 
Kcnn4tm1Rklr Kcnn4tm1Rklr/Kcnn4tm1Rklr
involves: 129S/SvEv * C57BL/6		 MGI:1277957  MP:0004875 increased mean systemic arterial blood pressure PMID: 16873714 
Kcnn4tm1Jemn Kcnn4tm1Jemn/Kcnn4tm1Jemn
involves: 129S1/Sv * C57BL/6J		 MGI:1277957  MP:0009531 increased parotid gland size PMID: 15347667 
Kcnn4tm1Rklr Kcnn4tm1Rklr/Kcnn4tm1Rklr
involves: 129S/SvEv * C57BL/6		 MGI:1277957  MP:0008809 increased spleen iron level PMID: 19037656 
Kcnn4tm1Rklr Kcnn4tm1Rklr/Kcnn4tm1Rklr
involves: 129S/SvEv * C57BL/6		 MGI:1277957  MP:0004952 increased spleen weight PMID: 19037656 
Kcnn4tm1Rklr Kcnn4tm1Rklr/Kcnn4tm1Rklr
involves: 129S/SvEv * C57BL/6		 MGI:1277957  MP:0006143 increased systemic arterial diastolic blood pressure PMID: 16873714 
Kcnn4tm1Rklr Kcnn4tm1Rklr/Kcnn4tm1Rklr
involves: 129S/SvEv * C57BL/6		 MGI:1277957  MP:0006144 increased systemic arterial systolic blood pressure PMID: 16873714 
Kcnn4tm1Rklr Kcnn4tm1Rklr/Kcnn4tm1Rklr
involves: 129S/SvEv * C57BL/6		 MGI:1277957  MP:0000248 macrocytosis PMID: 19037656 
Clinically-Relevant Mutations and Pathophysiology
Disease:  Dehydrated hereditary stomatocytosis
OMIM: 185000
Orphanet: ORPHA3202
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Deletion Human R253H and others 1,24,48
Disease:  Diamond-Blackfan anemia
Disease Ontology: DOID:1339
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Deletion Human - - Large hemizygous deletion from D19S19 to CYP2B6 on 19q13.2; this deletion was detected in one patient with Diamond-Blackfan anemia. 22
Disease:  Restenosis and angiogenesis
Role:  Involved in T and B cell activation; vascular smooth muscle and endothelial cell proliferation
Drugs:  TRAM-34
Side effects:  none reported in mice or rats
Therapeutic use:  Potential use of KCa3.1 blockers as immunosuppressants and for the prevention of restenosis and angiogenesis
References:  9,23,25,38,51,73,75
Disease:  Sickle cell anemia
Disease Ontology: DOID:10923
Role:  KCa3.1 is involved in erythrocyte dehydration during sickling
Drugs:  Clotrimazole, senicapoc
Side effects:  none reported
Therapeutic use:  Phase-3 clinical trials for ICA-17043 (senicapoc) were stopped in 2007 apparently due to lack of efficacy in reducing the incidence of sickling crisis
References:  2,5-6
Disease:  Traumatic and possibly ischemic brain injury
Role:  KCa3.1 is involved in respiratory burst and microglia mediated neuronal killing
Drugs:  cyclohexadione 16, TRAM-34
Side effects:  none reported
Therapeutic use:  KCa3.1 blockers suggested for the treatment of brain injury
Comments:  cyclohexadione 16, TRAM-34 efficacy has been demonstrated in rat models of traumatic brain injury or optic nerve transcetion
References:  31,33,41
Gene Expression and Pathophysiology
Reduced KCa3.1 expression in carotid artery of uremic rats and regenerated endothelium after ballon catheter injury
Tissue or cell type:  Carotid arteries
Pathophysiology:  Impaired EDHF response
Species:  Rat
Technique: 
References:  35-36

References

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1. Andolfo I, Russo R, Manna F, Shmukler BE, Gambale A, Vitiello G, De Rosa G, Brugnara C, Alper SL, Snyder LM et al.. (2015) Novel Gardos channel mutations linked to dehydrated hereditary stomatocytosis (xerocytosis). Am. J. Hematol., 90 (10): 921-6. [PMID:26178367]

2. Ataga KI, Orringer EP, Styles L, Vichinsky EP, Swerdlow P, Davis GA, Desimone PA, Stocker JW. (2006) Dose-escalation study of ICA-17043 in patients with sickle cell disease. Pharmacotherapy, 26 (11): 1557-64. [PMID:17064199]

3. Ayabe T, Wulff H, Darmoul D, Cahalan MD, Chandy KG, Ouellette AJ. (2002) Modulation of mouse Paneth cell alpha-defensin secretion by mIKCa1, a Ca2+-activated, intermediate conductance potassium channel. J. Biol. Chem., 277 (5): 3793-800. [PMID:11724775]

4. Begenisich T, Nakamoto T, Ovitt CE, Nehrke K, Brugnara C, Alper SL, Melvin JE. (2004) Physiological roles of the intermediate conductance, Ca2+-activated potassium channel Kcnn4. J. Biol. Chem., 279 (46): 47681-7. [PMID:15347667]

5. Brugnara C, de Franceschi L, Alper SL. (1993) Inhibition of Ca(2+)-dependent K+ transport and cell dehydration in sickle erythrocytes by clotrimazole and other imidazole derivatives. J. Clin. Invest., 92 (1): 520-6. [PMID:8326017]

6. Brugnara C, Gee B, Armsby CC, Kurth S, Sakamoto M, Rifai N, Alper SL, Platt OS. (1996) Therapy with oral clotrimazole induces inhibition of the Gardos channel and reduction of erythrocyte dehydration in patients with sickle cell disease. J. Clin. Invest., 97 (5): 1227-34. [PMID:8636434]

7. Bychkov R, Burnham MP, Richards GR, Edwards G, Weston AH, Félétou M, Vanhoutte PM. (2002) Characterization of a charybdotoxin-sensitive intermediate conductance Ca2+-activated K+ channel in porcine coronary endothelium: relevance to EDHF. Br. J. Pharmacol., 137 (8): 1346-54. [PMID:12466245]

8. Castle NA, London DO, Creech C, Fajloun Z, Stocker JW, Sabatier JM. (2003) Maurotoxin: a potent inhibitor of intermediate conductance Ca2+-activated potassium channels. Mol. Pharmacol., 63 (2): 409-18. [PMID:12527813]

9. Chandy KG, Wulff H, Beeton C, Pennington M, Gutman GA, Cahalan MD. (2004) K+ channels as targets for specific immunomodulation. Trends Pharmacol. Sci., 25 (5): 280-9. [PMID:15120495]

10. Chung I, Zelivyanskaya M, Gendelman HE. (2002) Mononuclear phagocyte biophysiology influences brain transendothelial and tissue migration: implication for HIV-1-associated dementia. J. Neuroimmunol., 122 (1-2): 40-54. [PMID:11777542]

11. Coleman N, Brown BM, Oliván-Viguera A, Singh V, Olmstead MM, Valero MS, Köhler R, Wulff H. (2014) New positive Ca2+-activated K+ channel gating modulators with selectivity for KCa3.1. Mol. Pharmacol., 86 (3): 342-57. [PMID:24958817]

12. DeCoursey TE, Chandy KG, Gupta S, Cahalan MD. (1985) Voltage-dependent ion channels in T-lymphocytes. J. Neuroimmunol., 10 (1): 71-95. [PMID:2414315]

13. Devor DC, Singh AK, Lambert LC, DeLuca A, Frizzell RA, Bridges RJ. (1999) Bicarbonate and chloride secretion in Calu-3 human airway epithelial cells. J. Gen. Physiol., 113 (5): 743-60. [PMID:10228185]

14. Di L, Srivastava S, Zhdanova O, Sun Y, Li Z, Skolnik EY. (2010) 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., 285 (50): 38765-71. [PMID:20884616]

15. Eichler I, Wibawa J, Grgic I, Knorr A, Brakemeier S, Pries AR, Hoyer J, Köhler R. (2003) Selective blockade of endothelial Ca2+-activated small- and intermediate-conductance K+-channels suppresses EDHF-mediated vasodilation. Br. J. Pharmacol., 138 (4): 594-601. [PMID:12598413]

16. Ellory JC, Culliford SJ, Smith PA, Wolowyk MW, Knaus EE. (1994) Specific inhibition of Ca-activated K channels in red cells by selected dihydropyridine derivatives. Br. J. Pharmacol., 111 (3): 903-5. [PMID:8019767]

17. Fanger CM, Ghanshani S, Logsdon NJ, Rauer H, Kalman K, Zhou J, Beckingham K, Chandy KG, Cahalan MD, Aiyar J. (1999) Calmodulin mediates calcium-dependent activation of the intermediate conductance KCa channel, IKCa1. J. Biol. Chem., 274 (9): 5746-54. [PMID:10026195]

18. Feske S, Wulff H, Skolnik EY. (2015) Ion channels in innate and adaptive immunity. Annu. Rev. Immunol., 33: 291-353. [PMID:25861976]

19. Fioretti B, Castigli E, Calzuola I, Harper AA, Franciolini F, Catacuzzeno L. (2004) NPPB block of the intermediate-conductance Ca2+-activated K+ channel. Eur. J. Pharmacol., 497 (1): 1-6. [PMID:15321728]

20. Friebel K, Schönherr R, Kinne RW, Kunisch E. (2015) Functional role of the KCa3.1 potassium channel in synovial fibroblasts from rheumatoid arthritis patients. J. Cell. Physiol., 230 (7): 1677-88. [PMID:25545021]

21. GARDOS G. (1958) The function of calcium in the potassium permeability of human erythrocytes. Biochim. Biophys. Acta, 30 (3): 653-4. [PMID:13618284]

22. Ghanshani S, Coleman M, Gustavsson P, Wu AC, Gargus JJ, Gutman GA, Dahl N, Mohrenweiser H, Chandy KG. (1998) Human calcium-activated potassium channel gene KCNN4 maps to chromosome 19q13.2 in the region deleted in diamond-blackfan anemia. Genomics, 51 (1): 160-1. [PMID:9693050]

23. Ghanshani S, Wulff H, Miller MJ, Rohm H, Neben A, Gutman GA, Cahalan MD, Chandy KG. (2000) Up-regulation of the IKCa1 potassium channel during T-cell activation. Molecular mechanism and functional consequences. J. Biol. Chem., 275 (47): 37137-49. [PMID:10961988]

24. Glogowska E, Lezon-Geyda K, Maksimova Y, Schulz VP, Gallagher PG. (2015) Mutations in the Gardos channel (KCNN4) are associated with hereditary xerocytosis. Blood, 126 (11): 1281-4. [PMID:26198474]

25. Grgic I, Eichler I, Heinau P, Si H, Brakemeier S, Hoyer J, Köhler R. (2005) Selective blockade of the intermediate-conductance Ca2+-activated K+ channel suppresses proliferation of microvascular and macrovascular endothelial cells and angiogenesis in vivo. Arterioscler. Thromb. Vasc. Biol., 25 (4): 704-9. [PMID:15662023]

26. Grissmer S, Nguyen AN, Cahalan MD. (1993) Calcium-activated potassium channels in resting and activated human T lymphocytes. Expression levels, calcium dependence, ion selectivity, and pharmacology. J. Gen. Physiol., 102 (4): 601-30. [PMID:7505804]

27. Ishii TM, Silvia C, Hirschberg B, Bond CT, Adelman JP, Maylie J. (1997) A human intermediate conductance calcium-activated potassium channel. Proc. Natl. Acad. Sci. U.S.A., 94 (21): 11651-6. [PMID:9326665]

28. Jensen BS, Strobaek D, Christophersen P, Jorgensen TD, Hansen C, Silahtaroglu A, Olesen SP, Ahring PK. (1998) Characterization of the cloned human intermediate-conductance Ca2+-activated K+ channel. Am. J. Physiol., 275 (3 Pt 1): C848-56. [PMID:9730970]

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Richard Aldrich, K. George Chandy, Stephan Grissmer, George A. Gutman, Aguan D. Wei, Heike Wulff.
Calcium- and sodium-activated potassium channels: KCa3.1. Last modified on 07/03/2019. Accessed on 21/07/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=384.