K<sub>Ca</sub>2.3 | Calcium- and sodium-activated potassium channels | IUPHAR/BPS Guide to PHARMACOLOGY

KCa2.3

Target id: 383

Nomenclature: KCa2.3

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

   GtoImmuPdb view: OFF :     Currently no data for KCa2.3 in GtoImmuPdb

Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 1 731 1q21.3 KCNN3 potassium calcium-activated channel subfamily N member 3 9,20
Mouse 6 1 732 3 F2 Kcnn3 potassium intermediate/small conductance calcium-activated channel, subfamily N, member 3 4,45
Rat 6 1 732 2q34 Kcnn3 potassium calcium-activated channel subfamily N member 3 2,30
Previous and Unofficial Names
SK3 | SKCa3 | small conductance calcium-activated potassium channel 3 | potassium channel, calcium activated intermediate/small conductance subfamily N alpha, member 3 | potassium intermediate/small conductance calcium-activated channel
Database Links
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Associated Proteins
Heteromeric Pore-forming Subunits
Name References
Not determined
Auxiliary Subunits
Name References
Not determined
Other Associated Proteins
Name References
calmodulin 50,66
Functional Characteristics
SKCa
Ion Selectivity and Conductance
Species:  Human
Rank order:  K+ > Rb+ > Cs+
References:  62
Voltage Dependence Comments
KCa2.3 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 Affinity Units Concentration range (M) Holding voltage (mV) Reference
EBIO Rn Agonist - - 5x10-5 - 21
Conc range: 5x10-5 M [21]
riluzole Rn Agonist - - 3x10-6 - 1x10-5 - 21
Conc range: 3x10-6 - 1x10-5 M [21]
NS309 Hs Agonist - - 3x10-8 - 53,61
Conc range: 3x10-8 M [53,61]
NS13001 Mm Agonist 6.8 pEC50 - - 27
pEC50 6.8 (EC50 1.4x10-7 M) [27]
Ca2+ Hs Agonist 6.0 – 6.5 pEC50 - - 25,62,66
pEC50 6.0 – 6.5 [25,62,66]
Ca2+ Rn Agonist 6.2 pEC50 - - 2
pEC50 6.2 [2]
SKA-31 Hs Agonist 5.5 pEC50 - - 46
pEC50 5.5 (EC50 3x10-6 M) [46]
CyPPA Hs Agonist 5.3 pEC50 - - 25
pEC50 5.3 [25]
DC-EBIO Hs Agonist 4.9 pEC50 - - 64
pEC50 4.9 [64]
riluzole Hs Agonist 4.9 pEC50 - - 46
pEC50 4.9 (EC50 1.25x10-5 M) [46]
EBIO Hs Agonist 3.8 pEC50 - - 61-62
pEC50 3.8 [61-62]
View species-specific activator tables
Activator Comments
NS309, riluzole, DC-EBIO and EBIO increase the Ca2+ sensitivity of KCa2 channels.

A detailed review of KCa2 channel pharmacology can be found in [64]. For shorter more recent reviews see [65] and [12].
Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Concentration range (M) Holding voltage (mV) Reference
apamin Hs - 7.9 – 9.1 pIC50 - - 57,62
pIC50 7.9 – 9.1 (IC50 1.32x10-8 – 8x10-10 M) [57,62]
UCL1684 Hs - 8.0 – 9.0 pIC50 - - 16,61
pIC50 8.0 – 9.0 [16,61]
Gating inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Concentration range (M) Holding voltage (mV) Reference
NS11757 Rn - 8.1 pKd - - 54
pKd 8.1 [54]
RA-2 Hs Antagonist 7.7 pIC50 - - 40
pIC50 7.7 (IC50 2x10-8 M) [40]
NS8593 Hs Antagonist 6.1 pIC50 - - 52
pIC50 6.1 [52]
View species-specific gating inhibitor tables
Gating Inhibitor Comments
NS5893 is an inhibitory gating modulator that decreases the Ca2+ sensitivity of KCa2 channels [52]. [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 [40].
Channel Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Concentration range (M) Holding voltage (mV) Reference
Lei-Dab7 Hs Agonist 8.4 pKd - - 48
pKd 8.4 (Kd 3.8x10-9 M) [48]
apamin Rn Antagonist 8.9 – 9.2 pIC50 - - 2,24
pIC50 8.9 – 9.2 [2,24]
leiurotoxin I Hs Antagonist 8.7 – 9.0 pIC50 - - 48,62
pIC50 8.7 – 9.0 [48,62]
tamapin Rn Antagonist 8.8 pIC50 - - 44
pIC50 8.8 [44]
UCL1848 Rn Antagonist 8.7 pIC50 - - 24
pIC50 8.7 [24]
UCL1684 Rn Antagonist 8.2 pIC50 - - 24
pIC50 8.2 [24]
leiurotoxin I Rn Antagonist 8.1 pIC50 - - 24
pIC50 8.1 [24]
P05 Hs Agonist 7.6 pIC50 - - 48
pIC50 7.6 [48]
dequalinium Hs Antagonist 4.5 pIC50 - - 57
pIC50 4.5 [57]
tubocurarine Hs Antagonist 3.7 – 4.5 pIC50 - - 57,62
pIC50 3.7 – 4.5 [57,62]
tetraethylammonium Hs - 2.7 pIC50 - - 61
pIC50 2.7 [61]
View species-specific channel blocker tables
Tissue Distribution
Omentum, rectum, myometrium, small intestine, skeletal muscle, endometrium, urinary bladder, hypothalamus, thyroid, uterus, crevix, tonsil, thymus, lung, adenoid, kidney, oesophagus, herat, colon, ovary, trachea, adrenal gland, spleen, testis, salivary gland, mammary gland and stomach, clitoris and corpus cavernosum.
Species:  Human
Technique:  Immunohistochemistry, RT-PCR
References:  11
Granulocyte-defferentialted PLB-985 cells
Species:  Human
Technique:  Electrophysiology, RT-PCR
References:  17
Cardiac myocytes
Species:  Human
Technique:  Electrophysiology, Pharmacology, Western blot and RT-PCR
References:  49
Neutrophils.
Species:  Human
Technique:  RT-PCR
References:  17
Cardiac myocytes (higher expression in atrial than ventricular myocytes)
Species:  Mouse
Technique:  Electrophysiology, Pharmacology, Western blot and RT-PCR
References:  69
Urinary bladder smooth muscle
Species:  Mouse
Technique:  Electrophysiology, Immunohistochemistry
References:  22
Dopaminergic neurons in the substantia nigra.
Species:  Mouse
Technique:  Electrophysiology, Immunohistochemistry, RT-PCR
References:  63
Denervated skeletal muscle.
Species:  Mouse
Technique:  Electrophysiology, Western blot
References:  26
Pancreatic islets and insulinomas (mouse and rat).
Species:  Rat
Technique:  Electrophysiology, Immunohistochemistry, RT-PCR
References:  55
Vascular endothelium (mouse and rat).
Species:  Rat
Technique:  Electrophysiology, Immunohistochemistry, Pharmacology, RT-PCR
References:  14,56
Brain (olfactory system, neocortex, hippocampus, septum, amygdala, thalamus, habenula, hypothalamus, brain stem, cerebellum, substantianigra, ependyma, ventral tegmental area, olfactory tubercle, caudate putamen)
Species:  Rat
Technique:  In situ hybridisation
References:  30,51
Astrocytes (mouse and rat)
Species:  Rat
Technique:  Immunohistochemistry
References:  1
Urinary bladder smooth muscle
Species:  Rat
Technique:  Electrophysiology, Immunohistochemistry
References:  43
Liver
Species:  Rat
Technique:  Immunohistochemistry
References:  2
Tissue Distribution Comments
Also expressed in vascular endothelium in mouse, dog, pig, rabbit (pulmonary vein) [6-7,13,41].
Functional Assays
Two-electrode voltage-clamp.
Species:  Rat
Tissue:  Xenopus oocytes injected with KCa2.3 mRNA.
Response measured:  KCa2.3 current.
References:  30,66
Patch-clamp recordings of mammalian cells transiently or stably transfected with KCa2.3.
Species:  Human
Tissue:  HEK-293 and CHO cells.
Response measured:  KCa2.3 current.
References:  16,25,48,52-53,57,62,64
Patch-clamp recording of mammalian cells transiently or stably transfected with KCa2.3.
Species:  Rat
Tissue:  HEK-293 and COS-7 cells.
Response measured:  KCa2.3 current.
References:  2,21,24,44,52
Patch-clamp recording.
Species:  Rat
Tissue:  Cultured superior cervical ganglion neurons.
Response measured:  mAHP current and neuronal firing frequency.
References:  24
Patch-clamp recordings from dopaminergic neurons in the substantia nigra and ventral tegmental area.
Species:  Mouse
Tissue:  Midbrain slices containing the substantia nigra pars compacta.
Response measured:  mAHP current and neuronal firing frequency.
References:  63
Patch-clamp recordings
Species:  Mouse
Tissue:  Bladder myocytes or flexor digitorium brevis muscle fibres (innervated of denervated skeletal muscle).
Response measured:  KCa2.3 current, muscle action potentials.
References:  22,26
Physiological Functions
KCa2.3 underlies the medium AHP current in dopaminergic neurons of the substantia nigra and regulates their firing frequency. KCa2.3 could potentially contribute to the medium AHP in other neurons.
Species:  Mouse
Tissue:  Dopaminergic neurons of the substantia nigra.
References:  50,60,63
KCa2.3 is involved in determining excitability and contractility of urinary bladder smooth muscle. Transgenic mice overexpressing KCa2.3 have greater bladder capacitance.
Species:  Mouse
Tissue:  Bladder smooth muscle
References:  22
KCa2.3 channels are probably important in neurons regulating respiration in response to hypoxia and parturition during labour.
Species:  Mouse
Tissue:  Neurons, uterine smooth muscle.
References:  4
KCa2.3 channels are involved in respiratory burst in rat microglia and human neutrophils.
Species:  Human
Tissue:  Microglia, neutrophils.
References:  17,28
KCa2.3, together with KCa3.1, underlies the endothelium-derived hyperpolarising factor (EDHF) response. EDHF-mediated vasodilation can be measured in various arterial preparations from rats and mice. Doxicyclin induced suppression of KCa2.3 expression in transgenic mice overexpressing KCa2.3 leads to elevation in blood pressure.
Species:  Rat
Tissue:  Mesenteric, carotid, cerebral, coronary and renal arteries. (also in mouse, human, pig, dog)
References:  6-7,13-14,41,56
Physiological Consequences of Altering Gene Expression
Transgenic mice overexpressing KCa2.3 have greater bladder capcitance and urge incontinence. Treatment with NS309 increases bladder capacity and micturition volume in rats.
Species:  Rat
Tissue:  Bladder
Technique:  Transgenic rats
References:  22,42,64
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Kcnn3tm1Jpad Kcnn3tm1Jpad/Kcnn3tm1Jpad
involves: 129S4/SvJae * C57BL/6
MGI:2153183  MP:0005572 abnormal breathing frequency PMID: 10988076 
Kcnn3tm1Jpad Kcnn3tm1Jpad/Kcnn3tm1Jpad
involves: 129S4/SvJae * C57BL/6
MGI:2153183  MP:0002907 abnormal parturition PMID: 10988076 
Kcnn3tm1Jpad Kcnn3tm1Jpad/Kcnn3tm1Jpad
involves: 129S4/SvJae * C57BL/6
MGI:2153183  MP:0001957 apnea PMID: 10988076 
Kcnn3tm1Jpad Kcnn3tm1Jpad/Kcnn3tm1Jpad
involves: 129S4/SvJae * C57BL/6
MGI:2153183  MP:0008028 pregnancy-related premature death PMID: 10988076 
Clinically-Relevant Mutations and Pathophysiology
Disease:  Atrial Fibrillation
Comments: 
References:  10,15,34-35,59,67
Disease:  Heritable pulmonary arterial hypertension
Orphanet: ORPHA275777
Role: 
Therapeutic use:  KCa2.3 activators have been proposed for the treatment of hypertension.
Comments: 
References:  6,56
Disease:  Major depressive disorder; MDD
Disease Ontology: DOID:1470
OMIM: 608516
Drugs: 
Side effects:  High doses of apamin induce seizures and lead to Purkinje cell degeneration in the cerebellum.
Therapeutic use:  KCa2.3 blockers have been proposed for the treatment of depression.
References:  3,19,33
Disease:  Parkinson Disease
Synonyms: Parkinson's disease [Disease Ontology: DOID:14330]
Disease Ontology: DOID:14330
OMIM: 168600
Role: 
Drugs: 
Side effects:  High doses of apamin induce seizures and lead to Purkinje cell degeneration in the cerebellum.
Therapeutic use:  KCa2.3 blockers have been proposed for the treatment of Parkinson disease.
References:  3,38,60,64
Disease:  Schizophrenia
Disease Ontology: DOID:5419
OMIM: 181500
Orphanet: ORPHA3140
Comments: 
References:  5,37
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Frameshift: Deletion Human L283fs287X 1137-1140delGTGA 5,37
Clinically-Relevant Mutations and Pathophysiology Comments
Longer polyglutamine repeats in KCa2.3 are associated with schizophrenia [8-9], anorexia nervosa [32] and spinocerebellar ataxia [18].
Gene Expression and Pathophysiology
Increased expression in patients with myotonic muscular dystrophy.
Tissue or cell type:  Patient muscle samples.
Pathophysiology:  KCa2.3 is probably involved in hyperexcitability.
Species:  Human
Technique: 
References:  29
Increased expression in skeletal muscle following denervation.
Tissue or cell type:  Flexor digitorum brevis muscle.
Pathophysiology:  KCa2.3 is probably involved in hyperexcitability.
Species:  Mouse
Technique: 
References:  39
Reduced expression in in vascular endothelium during angiotensin-II-induced hypertension and in diabetes.
Tissue or cell type:  Rat and mouse vascular endothelium.
Pathophysiology:  Reduced KCa2.3 expression could contribute to functional alterations in endothelium in hypertension.
Species:  Rat
Technique: 
References:  23
KCa2.3 expression changes during cardiac remodelling
Tissue or cell type:  Mouse atria and human patients with AF
Pathophysiology:  Reduced KCa2.3 expression in diabetic mouse atria and human patients with Atrial Fibrillation; mice over-expressing KCa2.3 seem to be more prone to sudden cardiac death.
Species:  Human
Technique: 
References:  35-36,49,68
Biologically Significant Variants
Type:  Splice variant
Species:  Human
Description:  Alternative splicing leads to the inclusion if an additional 15aa in the outer pore region. The channel, known as hSK3-ex4, is a functional channel whose message is expressed at 0-2% of hKCa2.3 levels. The channel is insensitive to apamin, scyllatoxin and tubocurarine.
Amino acids:  746
References:  62
Type:  Splice variant
Species:  Human
Description:  Isoform a
Amino acids:  731
Nucleotide accession: 
Protein accession: 
Type:  Splice variant
Species:  Human
Description:  Isoform b
Amino acids:  426
Nucleotide accession: 
Protein accession: 
Type:  Splice variant
Species:  Human
Description:  Alternative first exon usage produces two splice variant, SK3-1B and SK3-1C, that lack the N-terminus and SA. Both of these proteins can act as dominant-negative suppressors of the entire KCa2 sub-family, trapping channels intracellularly. The SK3-1B transgenic mouse exhibits ataxia due to suppression of KCa2 channels in depp cerebellar neurons. SK3-1B mRNA is present in brain at 20-60% of kKCa2.3 levels. These two variant proteins are suggested to regulate neuronal excitability through dominant-negative suppression of "normal" hKCa2.3.
References:  31,47,58

References

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1. Armstrong WE, Rubrum A, Teruyama R, Bond CT, Adelman JP. (2005) Immunocytochemical localization of small-conductance, calcium-dependent potassium channels in astrocytes of the rat supraoptic nucleus. J. Comp. Neurol., 491 (3): 175-85. [PMID:16134141]

2. Barfod ET, Moore AL, Lidofsky SD. (2001) Cloning and functional expression of a liver isoform of the small conductance Ca2+-activated K+ channel SK3. Am. J. Physiol., Cell Physiol., 280 (4): C836-42. [PMID:11245600]

3. Blank T, Nijholt I, Kye MJ, Spiess J. (2004) Small conductance Ca2+-activated K+ channels as targets of CNS drug development. Curr Drug Targets CNS Neurol Disord., 3 (3): 161-7. [PMID:15180477]

4. Bond CT, Sprengel R, Bissonnette JM, Kaufmann WA, Pribnow D, Neelands T, Storck T, Baetscher M, Jerecic J, Maylie J, Knaus HG, Seeburg PH, Adelman JP. (2000) Respiration and parturition affected by conditional overexpression of the Ca2+-activated K+ channel subunit, SK3. Science, 289 (5486): 1942-6. [PMID:10988076]

5. Bowen T, Williams N, Norton N, Spurlock G, Wittekindt OH, Morris-Rosendahl DJ, Williams H, Brzustowicz L, Hoogendoorn B, Zammit S, Jones G, Sanders RD, Jones LA, McCarthy G, Jones S, Bassett A, Cardno AG, Owen MJ, O'Donovan MC. (2001) Mutation screening of the KCNN3 gene reveals a rare frameshift mutation. Mol. Psychiatry, 6 (3): 259-60. [PMID:11326292]

6. Brähler S, Kaistha A, Schmidt VJ, Wölfle SE, Busch C, Kaistha BP, Kacik M, Hasenau AL, Grgic I, Si H et al.. (2009) Genetic deficit of SK3 and IK1 channels disrupts the endothelium-derived hyperpolarizing factor vasodilator pathway and causes hypertension. Circulation, 119 (17): 2323-32. [PMID:19380617]

7. Burnham MP, Bychkov R, Félétou M, Richards GR, Vanhoutte PM, Weston AH, Edwards G. (2002) Characterization of an apamin-sensitive small-conductance Ca(2+)-activated K(+) channel in porcine coronary artery endothelium: relevance to EDHF. Br. J. Pharmacol., 135 (5): 1133-43. [PMID:11877319]

8. Cardno AG, Bowen T, Guy CA, Jones LA, McCarthy G, Williams NM, Murphy KC, Spurlock G, Gray M, Sanders RD, Craddock N, McGuffin P, Owen MJ, O'Donovan MC. (1999) CAG repeat length in the hKCa3 gene and symptom dimensions in schizophrenia. Biol. Psychiatry, 45 (12): 1592-6. [PMID:10376120]

9. Chandy KG, Fantino E, Wittekindt O, Kalman K, Tong LL, Ho TH, Gutman GA, Crocq MA, Ganguli R, Nimgaonkar V, Morris-Rosendahl DJ, Gargus JJ. (1998) Isolation of a novel potassium channel gene hSKCa3 containing a polymorphic CAG repeat: a candidate for schizophrenia and bipolar disorder?. Mol. Psychiatry, 3 (1): 32-7. [PMID:9491810]

10. Chang SH, Chang SN, Hwang JJ, Chiang FT, Tseng CD, Lee JK, Lai LP, Lin JL, Wu CK, Tsai CT. (2012) Significant association of rs13376333 in KCNN3 on chromosome 1q21 with atrial fibrillation in a Taiwanese population. Circ. J., 76 (1): 184-8. [PMID:22019810]

11. Chen MX, Gorman SA, Benson B, Singh K, Hieble JP, Michel MC, Tate SN, Trezise DJ. (2004) Small and intermediate conductance Ca(2+)-activated K+ channels confer distinctive patterns of distribution in human tissues and differential cellular localisation in the colon and corpus cavernosum. Naunyn Schmiedebergs Arch. Pharmacol., 369 (6): 602-15. [PMID:15127180]

12. Christophersen P, Wulff H. (2015) Pharmacological gating modulation of small- and intermediate-conductance Ca(2+)-activated K(+) channels (KCa2.x and KCa3.1). Channels (Austin), 9 (6): 336-43. [PMID:26217968]

13. Damkjaer M, Nielsen G, Bodendiek S, Staehr M, Gramsbergen JB, de Wit C, Jensen BL, Simonsen U, Bie P, Wulff H et al.. (2012) Pharmacological activation of KCa3.1/KCa2.3 channels produces endothelial hyperpolarization and lowers blood pressure in conscious dogs. Br. J. Pharmacol., 165 (1): 223-34. [PMID:21699504]

14. 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]

15. Ellinor PT, Lunetta KL, Glazer NL, Pfeufer A, Alonso A, Chung MK, Sinner MF, de Bakker PI, Mueller M, Lubitz SA et al.. (2010) Common variants in KCNN3 are associated with lone atrial fibrillation. Nat. Genet., 42 (3): 240-4. [PMID:20173747]

16. Fanger CM, Rauer H, Neben AL, Miller MJ, Rauer H, Wulff H, Rosa JC, Ganellin CR, Chandy KG, Cahalan MD. (2001) Calcium-activated potassium channels sustain calcium signaling in T lymphocytes. Selective blockers and manipulated channel expression levels. J. Biol. Chem., 276 (15): 12249-56. [PMID:11278890]

17. Fay AJ, Qian X, Jan YN, Jan LY. (2006) SK channels mediate NADPH oxidase-independent reactive oxygen species production and apoptosis in granulocytes. Proc. Natl. Acad. Sci. U.S.A., 103 (46): 17548-53. [PMID:17085590]

18. Figueroa KP, Chan P, Schöls L, Tanner C, Riess O, Perlman SL, Geschwind DH, Pulst SM. (2001) Association of moderate polyglutamine tract expansions in the slow calcium-activated potassium channel type 3 with ataxia. Arch. Neurol., 58 (10): 1649-53. [PMID:11594924]

19. Galeotti N, Ghelardini C, Caldari B, Bartolini A. (1999) Effect of potassium channel modulators in mouse forced swimming test. Br. J. Pharmacol., 126 (7): 1653-9. [PMID:10323599]

20. 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]

21. Grunnet M, Jespersen T, Angelo K, Frøkjaer-Jensen C, Klaerke DA, Olesen SP, Jensen BS. (2001) Pharmacological modulation of SK3 channels. Neuropharmacology, 40 (7): 879-87. [PMID:11378158]

22. Herrera GM, Pozo MJ, Zvara P, Petkov GV, Bond CT, Adelman JP, Nelson MT. (2003) Urinary bladder instability induced by selective suppression of the murine small conductance calcium-activated potassium (SK3) channel. J. Physiol. (Lond.), 551 (Pt 3): 893-903. [PMID:12813145]

23. Hilgers RH, Webb RC. (2007) Reduced expression of SKCa and IKCa channel proteins in rat small mesenteric arteries during angiotensin II-induced hypertension. Am. J. Physiol. Heart Circ. Physiol., 292 (5): H2275-84. [PMID:17209000]

24. Hosseini R, Benton DC, Dunn PM, Jenkinson DH, Moss GW. (2001) SK3 is an important component of K(+) channels mediating the afterhyperpolarization in cultured rat SCG neurones. J. Physiol. (Lond.), 535 (Pt 2): 323-34. [PMID:11533126]

25. Hougaard C, Eriksen BL, Jørgensen S, Johansen TH, Dyhring T, Madsen LS, Strøbaek D, Christophersen P. (2007) Selective positive modulation of the SK3 and SK2 subtypes of small conductance Ca2+-activated K+ channels. Br. J. Pharmacol., 151 (5): 655-65. [PMID:17486140]

26. Jacobson D, Herson PS, Neelands TR, Maylie J, Adelman JP. (2002) SK channels are necessary but not sufficient for denervation-induced hyperexcitability. Muscle Nerve, 26 (6): 817-22. [PMID:12451607]

27. Kasumu AW, Hougaard C, Rode F, Jacobsen TA, Sabatier JM, Eriksen BL, Strøbæk D, Liang X, Egorova P, Vorontsova D et al.. (2012) Selective positive modulator of calcium-activated potassium channels exerts beneficial effects in a mouse model of spinocerebellar ataxia type 2. Chem. Biol., 19 (10): 1340-53. [PMID:23102227]

28. Khanna R, Roy L, Zhu X, Schlichter LC. (2001) K+ channels and the microglial respiratory burst. Am. J. Physiol., Cell Physiol., 280 (4): C796-806. [PMID:11245596]

29. Kimura T, Takahashi MP, Okuda Y, Kaido M, Fujimura H, Yanagihara T, Sakoda S. (2000) The expression of ion channel mRNAs in skeletal muscles from patients with myotonic muscular dystrophy. Neurosci. Lett., 295 (3): 93-6. [PMID:11090982]

30. Kohler M, Hirschberg B, Bond CT, Kinzie JM, Marrion NV, Maylie J, Adelman JP. (1996) Small-conductance, calcium-activated potassium channels from mammalian brain. Science, 273 (5282): 1709-14. [PMID:8781233]

31. Kolski-Andreaco A, Tomita H, Shakkottai VG, Gutman GA, Cahalan MD, Gargus JJ, Chandy KG. (2004) SK3-1C, a dominant-negative suppressor of SKCa and IKCa channels. J. Biol. Chem., 279 (8): 6893-904. [PMID:14638680]

32. Koronyo-Hamaoui M, Danziger Y, Frisch A, Stein D, Leor S, Laufer N, Carel C, Fennig S, Minoumi M, Apter A, Goldman B, Barkai G, Weizman A, Gak E. (2002) Association between anorexia nervosa and the hsKCa3 gene: a family-based and case control study. Mol. Psychiatry, 7 (1): 82-5. [PMID:11803450]

33. Lam J, Coleman N, Garing AL, Wulff H. (2013) The therapeutic potential of small-conductance KCa2 channels in neurodegenerative and psychiatric diseases. Expert Opin. Ther. Targets, 17 (10): 1203-20. [PMID:23883298]

34. Li C, Wang F, Yang Y, Fu F, Xu C, Shi L, Li S, Xia Y, Wu G, Cheng X et al.. (2011) Significant association of SNP rs2106261 in the ZFHX3 gene with atrial fibrillation in a Chinese Han GeneID population. Hum. Genet., 129 (3): 239-46. [PMID:21107608]

35. Ling TY, Wang XL, Chai Q, Lau TW, Koestler CM, Park SJ, Daly RC, Greason KL, Jen J, Wu LQ et al.. (2013) Regulation of the SK3 channel by microRNA-499--potential role in atrial fibrillation. Heart Rhythm, 10 (7): 1001-9. [PMID:23499625]

36. Mahida S, Mills RW, Tucker NR, Simonson B, Macri V, Lemoine MD, Das S, Milan DJ, Ellinor PT. (2014) Overexpression of KCNN3 results in sudden cardiac death. Cardiovasc. Res., 101 (2): 326-34. [PMID:24296650]

37. Miller MJ, Rauer H, Tomita H, Rauer H, Gargus JJ, Gutman GA, Cahalan MD, Chandy KG. (2001) Nuclear localization and dominant-negative suppression by a mutant SKCa3 N-terminal channel fragment identified in a patient with schizophrenia. J. Biol. Chem., 276 (30): 27753-6. [PMID:11395478]

38. Mourre C, Fournier C, Soumireu-Mourat B. (1997) Apamin, a blocker of the calcium-activated potassium channel, induces neurodegeneration of Purkinje cells exclusively. Brain Res., 778 (2): 405-8. [PMID:9459560]

39. Neelands TR, Herson PS, Jacobson D, Adelman JP, Maylie J. (2001) Small-conductance calcium-activated potassium currents in mouse hyperexcitable denervated skeletal muscle. J. Physiol. (Lond.), 536 (Pt 2): 397-407. [PMID:11600675]

40. Oliván-Viguera A, Valero MS, Coleman N, Brown BM, Laría C, Murillo MD, Gálvez JA, Díaz-de-Villegas MD, Wulff H, Badorrey R et al.. (2015) A novel pan-negative-gating modulator of KCa2/3 channels, fluoro-di-benzoate, RA-2, inhibits endothelium-derived hyperpolarization-type relaxation in coronary artery and produces bradycardia in vivo. Mol. Pharmacol., 87 (2): 338-48. [PMID:25468883]

41. Ozgen N, Dun W, Sosunov EA, Anyukhovsky EP, Hirose M, Duffy HS, Boyden PA, Rosen MR. (2007) Early electrical remodeling in rabbit pulmonary vein results from trafficking of intracellular SK2 channels to membrane sites. Cardiovasc. Res., 75 (4): 758-69. [PMID:17588552]

42. Pandita RK, Rønn LC, Jensen BS, Andersson KE. (2006) Urodynamic effects of intravesical administration of the new small/intermediate conductance calcium activated potassium channel activator NS309 in freely moving, conscious rats. J. Urol., 176 (3): 1220-4. [PMID:16890729]

43. Parajuli SP, Hristov KL, Soder RP, Kellett WF, Petkov GV. (2013) NS309 decreases rat detrusor smooth muscle membrane potential and phasic contractions by activating SK3 channels. Br. J. Pharmacol., 168 (7): 1611-25. [PMID:23145946]

44. Pedarzani P, D'hoedt D, Doorty KB, Wadsworth JD, Joseph JS, Jeyaseelan K, Kini RM, Gadre SV, Sapatnekar SM, Stocker M, Strong PN. (2002) Tamapin, a venom peptide from the Indian red scorpion (Mesobuthus tamulus) that targets small conductance Ca2+-activated K+ channels and afterhyperpolarization currents in central neurons. J. Biol. Chem., 277 (48): 46101-9. [PMID:12239213]

45. Ro S, Hatton WJ, Koh SD, Horowitz B. (2001) Molecular properties of small-conductance Ca2+-activated K+ channels expressed in murine colonic smooth muscle. Am. J. Physiol. Gastrointest. Liver Physiol., 281 (4): G964-73. [PMID:11557517]

46. Sankaranarayanan A, Raman G, Busch C, Schultz T, Zimin PI, Hoyer J, Köhler R, Wulff H. (2009) Naphtho[1,2-d]thiazol-2-ylamine (SKA-31), a new activator of KCa2 and KCa3.1 potassium channels, potentiates the endothelium-derived hyperpolarizing factor response and lowers blood pressure. Mol. Pharmacol., 75 (2): 281-95. [PMID:18955585]

47. Shakkottai VG, Chou CH, Oddo S, Sailer CA, Knaus HG, Gutman GA, Barish ME, LaFerla FM, Chandy KG. (2004) Enhanced neuronal excitability in the absence of neurodegeneration induces cerebellar ataxia. J. Clin. Invest., 113 (4): 582-90. [PMID:14966567]

48. Shakkottai VG, Regaya I, Wulff H, Fajloun Z, Tomita H, Fathallah M, Cahalan MD, Gargus JJ, Sabatier JM, Chandy KG. (2001) Design and characterization of a highly selective peptide inhibitor of the small conductance calcium-activated K+ channel, SkCa2. J. Biol. Chem., 276 (46): 43145-51. [PMID:11527975]

49. Skibsbye L, Poulet C, Diness JG, Bentzen BH, Yuan L, Kappert U, Matschke K, Wettwer E, Ravens U, Grunnet M et al.. (2014) Small-conductance calcium-activated potassium (SK) channels contribute to action potential repolarization in human atria. Cardiovasc. Res., 103 (1): 156-67. [PMID:24817686]

50. Stocker M. (2004) Ca(2+)-activated K+ channels: molecular determinants and function of the SK family. Nat. Rev. Neurosci., 5 (10): 758-70. [PMID:15378036]

51. Stocker M, Pedarzani P. (2000) Differential distribution of three Ca(2+)-activated K(+) channel subunits, SK1, SK2, and SK3, in the adult rat central nervous system. Mol. Cell. Neurosci., 15 (5): 476-93. [PMID:10833304]

52. Strøbaek D, Hougaard C, Johansen TH, Sørensen US, Nielsen EØ, Nielsen KS, Taylor RD, Pedarzani P, Christophersen P. (2006) Inhibitory gating modulation of small conductance Ca2+-activated K+ channels by the synthetic compound (R)-N-(benzimidazol-2-yl)-1,2,3,4-tetrahydro-1-naphtylamine (NS8593) reduces afterhyperpolarizing current in hippocampal CA1 neurons. Mol. Pharmacol., 70 (5): 1771-82. [PMID:16926279]

53. Strøbaek D, Teuber L, Jørgensen TD, Ahring PK, Kjaer K, Hansen RS, Olesen SP, Christophersen P, Skaaning-Jensen B. (2004) Activation of human IK and SK Ca2+ -activated K+ channels by NS309 (6,7-dichloro-1H-indole-2,3-dione 3-oxime). Biochim. Biophys. Acta, 1665 (1-2): 1-5. [PMID:15471565]

54. Sørensen US, Strøbaek D, Christophersen P, Hougaard C, Jensen ML, Nielsen EØ, Peters D, Teuber L. (2008) Synthesis and structure-activity relationship studies of 2-(N-substituted)-aminobenzimidazoles as potent negative gating modulators ofsmall conductance Ca2+-activated K+ channels. J. Med. Chem., 51 (23): 7625-34. [PMID:18998663]

55. Tamarina NA, Wang Y, Mariotto L, Kuznetsov A, Bond C, Adelman J, Philipson LH. (2003) Small-conductance calcium-activated K+ channels are expressed in pancreatic islets and regulate glucose responses. Diabetes, 52 (8): 2000-6. [PMID:12882916]

56. Taylor MS, Bonev AD, Gross TP, Eckman DM, Brayden JE, Bond CT, Adelman JP, Nelson MT. (2003) Altered expression of small-conductance Ca2+-activated K+ (SK3) channels modulates arterial tone and blood pressure. Circ. Res., 93 (2): 124-31. [PMID:12805243]

57. Terstappen GC, Pula G, Carignani C, Chen MX, Roncarati R. (2001) Pharmacological characterisation of the human small conductance calcium-activated potassium channel hSK3 reveals sensitivity to tricyclic antidepressants and antipsychotic phenothiazines. Neuropharmacology, 40 (6): 772-83. [PMID:11369031]

58. Tomita H, Shakkottai VG, Gutman GA, Sun G, Bunney WE, Cahalan MD, Chandy KG, Gargus JJ. (2003) Novel truncated isoform of SK3 potassium channel is a potent dominant-negative regulator of SK currents: implications in schizophrenia. Mol. Psychiatry, 8 (5): 524-35, 460. [PMID:12808432]

59. Tsai CT, Hsieh CS, Chang SN, Chuang EY, Juang JM, Lin LY, Lai LP, Hwang JJ, Chiang FT, Lin JL. (2015) Next-generation sequencing of nine atrial fibrillation candidate genes identified novel de novo mutations in patients with extreme trait of atrial fibrillation. J. Med. Genet., 52 (1): 28-36. [PMID:25391453]

60. Waroux O, Massotte L, Alleva L, Graulich A, Thomas E, Liégeois JF, Scuvée-Moreau J, Seutin V. (2005) SK channels control the firing pattern of midbrain dopaminergic neurons in vivo. Eur. J. Neurosci., 22 (12): 3111-21. [PMID:16367777]

61. Weatherall KL, Goodchild SJ, Jane DE, Marrion NV. (2010) Small conductance calcium-activated potassium channels: from structure to function. Prog. Neurobiol., 91 (3): 242-55. [PMID:20359520]

62. Wittekindt OH, Visan V, Tomita H, Imtiaz F, Gargus JJ, Lehmann-Horn F, Grissmer S, Morris-Rosendahl DJ. (2004) An apamin- and scyllatoxin-insensitive isoform of the human SK3 channel. Mol. Pharmacol., 65 (3): 788-801. [PMID:14978258]

63. Wolfart J, Neuhoff H, Franz O, Roeper J. (2001) Differential expression of the small-conductance, calcium-activated potassium channel SK3 is critical for pacemaker control in dopaminergic midbrain neurons. J. Neurosci., 21 (10): 3443-56. [PMID:11331374]

64. Wulff H, Kolski-Andreaco A, Sankaranarayanan A, Sabatier JM, Shakkottai V. (2007) Modulators of small- and intermediate-conductance calcium-activated potassium channels and their therapeutic indications. Curr. Med. Chem., 14 (13): 1437-57. [PMID:17584055]

65. Wulff H, Köhler R. (2013) Endothelial small-conductance and intermediate-conductance KCa channels: an update on their pharmacology and usefulness as cardiovascular targets. J. Cardiovasc. Pharmacol., 61 (2): 102-12. [PMID:23107876]

66. Xia XM, Fakler B, Rivard A, Wayman G, Johnson-Pais T, Keen JE, Ishii T, Hirschberg B, Bond CT, Lutsenko S, Maylie J, Adelman JP. (1998) Mechanism of calcium gating in small-conductance calcium-activated potassium channels. Nature, 395 (6701): 503-7. [PMID:9774106]

67. Yao JL, Zhou YF, Yang XJ, Qian XD, Jiang WP. (2015) KCNN3 SNP rs13376333 on Chromosome 1q21 Confers Increased Risk of Atrial Fibrillation. Int Heart J, 56 (5): 511-5. [PMID:26370375]

68. Yi F, Ling TY, Lu T, Wang XL, Li J, Claycomb WC, Shen WK, Lee HC. (2015) Down-regulation of the small conductance calcium-activated potassium channels in diabetic mouse atria. J. Biol. Chem., 290 (11): 7016-26. [PMID:25605734]

69. Zhang XD, Timofeyev V, Li N, Myers RE, Zhang DM, Singapuri A, Lau VC, Bond CT, Adelman J, Lieu DK et al.. (2014) Critical roles of a small conductance Ca²⁺-activated K⁺ channel (SK3) in the repolarization process of atrial myocytes. Cardiovasc. Res., 101 (2): 317-25. [PMID:24282291]

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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: KCa2.3. Last modified on 17/01/2017. Accessed on 18/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=383.