KCa2.2

Target id: 382

Nomenclature: KCa2.2

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 KCa2.2 in GtoImmuPdb

Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 1 579 5q22.3 KCNN2 potassium calcium-activated channel subfamily N member 2 14,22,32
Mouse 6 1 574 18 C Kcnn2 potassium intermediate/small conductance calcium-activated channel, subfamily N, member 2 7,47,55
Rat 6 1 580 18q11 Kcnn2 potassium calcium-activated channel subfamily N member 2 34,55
Previous and Unofficial Names
SK2 | SKCa2 | small conductance calcium-activated potassium channel 2 | potassium channel, calcium activated intermediate/small conductance subfamily N alpha, member 2
Database Links
ChEMBL Target
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
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 50,55,68
Associated Protein Comments
Casein kinase 2 (CK2) and protein phosphatase 2A (PPA) phosphorylate and dephosphorylate Thr80 in calmodulin changing KCa2.2 Ca2+ sensitivity [1,5].
Functional Characteristics
SKCa
Ion Selectivity and Conductance
Species:  Human
Rank order:  K+ [9.5 pS] > Rb+ > NH4+ > Cs+
References:  14,32
Species:  Rat
Rank order:  K+ [9.9 pS]
References:  34
Voltage Dependence Comments
KCa2.2 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
Ca2+ Hs Agonist 6.2 – 6.5 pEC50 - - 14,44,68
pEC50 6.2 – 6.5 [14,44,68]
Ca2+ Rn Agonist 6.1 – 6.4 pEC50 - - 26,34
pEC50 6.1 – 6.4 [26,34]
NS309 Hs Agonist 6.2 pEC50 3x10-8 - 1x10-7 - 44,62,65
pEC50 6.2 Conc range: 3x10-8 - 1x10-7 M [44,62,65]
NS13001 Mm Agonist 5.7 pEC50 - - 33
pEC50 5.7 (EC50 1.8x10-6 M) [33]
SKA-31 Hs Agonist 5.7 pEC50 - - 49
pEC50 5.7 (EC50 2x10-6 M) [49]
CyPPA Hs Agonist 4.9 pEC50 - - 30
pEC50 4.9 [30]
riluzole Rn Agonist 4.9 pEC50 - - 49
pEC50 4.9 (EC50 1.28x10-5 M) [49]
DC-EBIO Hs Agonist 4.6 pEC50 - - 44
pEC50 4.6 [44]
chlorzoxazone Rn - 3.0 – 4.1 pEC50 - - 8,63
pEC50 3.0 – 4.1 [8,63]
EBIO Hs Agonist 3.3 pEC50 - - 44,65
pEC50 3.3 [44,65]
zoxazolamine Rn Agonist 3.2 pEC50 1x10-4 - 6x10-4 - 8,63
pEC50 3.2 Conc range: 1x10-4 - 6x10-4 M [8,63]
EBIO Rn Agonist 3.0 pEC50 2x10-3 - 8,45
pEC50 3.0 Conc range: 2x10-3 M [8,45]
View species-specific activator tables
Activator Comments
NS309, riluzole, DC-EBIO and EBIO increase Ca2+ sensitivity of KCa2.2 [44-45]. A detailed review of KCa2 channel pharmacology can be found in [66]. For shorter more recent reviews see [11,67].
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 - 9.4 pKd - - 32
pKd 9.4 (Kd 3x10-10 M) [32]
UCL1684 Hs - 9.6 pIC50 - - 20,65
pIC50 9.6 [20,65]
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
RA-2 Mm Antagonist 7.7 pIC50 - - 41
pIC50 7.7 (IC50 2x10-8 M) [41]
NS8593 Hs Antagonist 6.2 pIC50 - - 60
pIC50 6.2 [60]
View species-specific gating inhibitor tables
Gating Inhibitor Comments
NS5893 is an inhibitory gating modulator that decreases the Ca2+ sensitivity of KCa2 channels [60].
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
tamapin Rn Antagonist 10.6 pIC50 - - 43
pIC50 10.6 [43]
apamin Rn Antagonist 10.1 – 10.2 pIC50 - - 34,61
pIC50 10.1 – 10.2 [34,61]
UCL1848 Rn Antagonist 9.9 – 10.0 pIC50 - - 38
pIC50 9.9 – 10.0 [38]
leiurotoxin I Hs Antagonist 9.5 – 9.7 pIC50 - - 32,53
pIC50 9.5 – 9.7 [32,53]
UCL1848 Hs Antagonist 9.6 pIC50 - - 20
pIC50 9.6 [20]
leiurotoxin I Rn Antagonist 9.5 pIC50 - - 61
pIC50 9.5 [61]
UCL1684 Rn Antagonist 9.4 pIC50 - - 61
pIC50 9.4 [61]
Lei-Dab7 Hs Antagonist 8.3 pIC50 - - 53
pIC50 8.3 [53]
P05 Hs Antagonist 7.7 pIC50 - - 53
pIC50 7.7 [53]
dequalinium Rn Antagonist 6.5 – 6.8 pIC50 - - 19,61
pIC50 6.5 – 6.8 [19,61]
tubocurarine Hs Antagonist 5.7 pIC50 - - 32
pIC50 5.7 [32]
tubocurarine Rn Antagonist 4.8 – 5.6 pIC50 - - 31,34,61
pIC50 4.8 – 5.6 [31,34,61]
bicuculline Rn Antagonist 4.6 pIC50 - - 61
pIC50 4.6 [61]
tetraethylammonium Hs - 2.7 pIC50 - - 65
pIC50 2.7 [65]
View species-specific channel blocker tables
Channel Blocker Comments
Tamapin, apamin and leiurotoxin I block KCa2.2 at picomolar concentrations and KCa2.1 and KCa2.3 at low nanomolar concentrations.

A detailed review of KCa2 channel pharmacology can be found in [66]. For shorter more recent reviews see [11,67].
Tissue Distribution
Adult and fetal brain, adrenal gland, prostate, bladder, liver, prostate, heart.
Species:  Human
Technique:  RT-PCR
References:  10
Intrahepatic bile duct cells.
Species:  Human
Technique:  Electrophysiology and immunohistochemistry.
References:  21
Brain, liver, spinal cord (longer transcripts in heart, skeletal muscle and pancreas) > Jurkat T cells, kidney
Species:  Human
Technique:  Northern Blot
References:  10,14
Cardiac myocytes.
Species:  Human
Technique:  Electrophysiology, Pharmacology, Western blot and RT-PCR
References:  69
CA1 hippocampal neurons and Purkinje cells.
Species:  Rat
Technique:  In situ hybridization, electrophysiology, pharmacology and immunohistochemistry.
References:  12,57
Brain and adrenal gland.
Species:  Rat
Technique:  Northern Blot
References:  34
Brain (olfactory system, neocortex, hippocampus, septum, amygdala, thalamus, habenula, hypothalamus, brain stem, cerebellum, ependyma)
Species:  Rat
Technique:  In situ hybridisation
References:  58
Brain (hippocampus > olfactory bulb, anterior olfactory nucleus, granular layer of cerebellum, reticular nucleus of the thalamus, pontine nucleus)
Species:  Rat
Technique:  In situ hybridisation
References:  34
Functional Assays
Patch-clamp recordings from cardiac myocytes.
Species:  Mouse
Tissue:  Heart.
Response measured:  Medium AHP current and action potential duration.
References:  69
Two-electrode voltage-clamp of Xenopus oocytes injected with KCa2.2 mRNA.
Species:  Rat
Tissue:  Xenopus oocytes.
Response measured:  KCa2.2
References:  34,45,63
Two-electrode voltage-clamp of Xenopus oocytes injected with KCa2.2 mRNA.
Species:  Human
Tissue:  Xenopus oocytes.
Response measured:  KCa2.2 mRNA.
References:  31,44
Patch-clamp recordings from cultured hippocampal CA1 neurons or brain slices.
Species:  Rat
Tissue:  CA1 neurons.
Response measured:  Medium AHP current and neuronal firing frequency.
References:  43-45,57
Patch-clamp recordings from cultured hippocampal CA1 neurons or brain slices.
Species:  Mouse
Tissue:  CA1 neurons.
Response measured:  Medium AHP current and neuronal firing frequency.
References:  7,60
Patch-clamp recordings from Jurkat T cells.
Species:  Human
Tissue:  Leukemic Jurkat T cells.
Response measured:  KCa2.2 current.
References:  14,20,23,32,53
Patch-clamp recordings of mammalian cells transiently or stably transfected with KCa2.2.
Species:  Rat
Tissue:  tsA201, HEK293, COS-7, CHO cells.
Response measured:  KCa2.2 current.
References:  8-9,19,38,61
Patch-clamp recordings of mammalian cells transiently or stably transfected with KCa2.2.
Species:  Human
Tissue:  tsA201, HEK293, COS-7, CHO cells.
Response measured:  KCa2.2 current.
References:  14,20,30,32,44,53,60,62
Patch-clamp recordings from cardiac myocytes.
Species:  Human
Tissue:  Heart.
Response measured:  Medium AHP current and action potential duration.
References:  69
Physiological Functions
KCa2.2 channels underly the apamin-sensitive medium AHP current that follows neuronal action potentials and regulates firing frequency. mAHP is abolished in KCa2.2 -/- mice and in mice where KCa2 currents are dominantly-negatively suppressed.
Species:  Mouse
Tissue:  Brain (hippocampus, deep cerebellar neurons)
References:  7,24,64
KCa2.2 channels underly the medium AHP current in CA1 hippocampal neurons and Purkinje cells and regulate neuronal firing frequency.
Species:  Rat
Tissue:  Hippocampus, cerebellum.
References:  12,57
KCa2.2 channels underly the mAHP current in cardiac myocytes and regulate action potential duration.
Species:  Mouse
Tissue:  Heart
References:  69
KCa2.2 channels underly the mAHP current in cardiac myocytes and regulate action potential duration.
Species:  Human
Tissue:  Heart
References:  69
KCa2.2 mediates part of the Ca2+ stimulated transepithelial secretion.
Species:  Human
Tissue:  Intrahepatic bile duct cells (choangiocytes).
References:  21
Physiological Consequences of Altering Gene Expression
Increased expression of KCa2.2 leads to - increased ImAHP amplitude - impaired induction of hippocampal LTP - impaired spatial learning and memory - impaired contextual and cued fear conditioning
Species:  Mouse
Tissue:  Brain
Technique:  Transgenic mice overexpressing KCa2.2.
References:  24
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Kcnn2tm1.1Jpad Kcnn2tm1.1Jpad/Kcnn2tm1.1Jpad
Not Specified
MGI:2153182  MP:0003412 abnormal afterhyperpolarization PMID: 15190101 
Kcnn2+|Kcnn2tm2Jpad Kcnn2tm2Jpad/Kcnn2+
B6.129S4-Kcnn2
MGI:2153182  MP:0002206 abnormal CNS synaptic transmission PMID: 16467533 
Kcnn2m1Btlr Kcnn2m1Btlr/Kcnn2m1Btlr
C57BL/6J-Kcnn2
MGI:2153182  MP:0001510 abnormal coat appearance
Kcnn2+|Kcnn2tm2Jpad Kcnn2tm2Jpad/Kcnn2+
B6.129S4-Kcnn2
MGI:2153182  MP:0001469 abnormal contextual conditioning behavior PMID: 16467533 
Kcnn2+|Kcnn2tm2Jpad Kcnn2tm2Jpad/Kcnn2+
B6.129S4-Kcnn2
MGI:2153182  MP:0001454 abnormal cued conditioning behavior PMID: 16467533 
Kcnn2+|Kcnn2tm2Jpad Kcnn2tm2Jpad/Kcnn2+
B6.129S4-Kcnn2
MGI:2153182  MP:0002912 abnormal excitatory postsynaptic potential PMID: 16467533 
Kcnn2m1Btlr Kcnn2m1Btlr/Kcnn2m1Btlr
C57BL/6J-Kcnn2
MGI:2153182  MP:0001406 abnormal gait
Kcnn2m1Btlr Kcnn2m1Btlr/Kcnn2m1Btlr
C57BL/6J-Kcnn2
MGI:2153182  MP:0002566 abnormal sexual interaction
Kcnn2+|Kcnn2tm2Jpad Kcnn2tm2Jpad/Kcnn2+
B6.129S4-Kcnn2
MGI:2153182  MP:0001463 abnormal spatial learning PMID: 16467533 
Kcnn2+|Kcnn2tm2Jpad Kcnn2tm2Jpad/Kcnn2+
B6.129S4-Kcnn2
MGI:2153182  MP:0003491 abnormal voluntary movement PMID: 16467533 
Kcnn2m1Btlr Kcnn2m1Btlr/Kcnn2m1Btlr
C57BL/6J-Kcnn2
MGI:2153182  MP:0001265 decreased body size
Kcnn2m1Btlr Kcnn2m1Btlr/Kcnn2m1Btlr
C57BL/6J-Kcnn2
MGI:2153182  MP:0001505 hunched posture
Kcnn2tm1Jpad Kcnn2tm1Jpad/Kcnn2tm1Jpad
Not Specified
MGI:2153182  MP:0002169 no abnormal phenotype detected PMID: 15190101 
Kcnn2tm2Jpad Kcnn2tm2Jpad/Kcnn2tm2Jpad
B6.129S4-Kcnn2
MGI:2153182  MP:0002080 prenatal lethality PMID: 16467533 
Kcnn2+|Kcnn2tm2Jpad Kcnn2tm2Jpad/Kcnn2+
B6.129S4-Kcnn2
MGI:2153182  MP:0001473 reduced long term potentiation PMID: 16467533 
Kcnn2m1Btlr Kcnn2m1Btlr/Kcnn2m1Btlr
C57BL/6J-Kcnn2
MGI:2153182  MP:0000745 tremors
Clinically-Relevant Mutations and Pathophysiology
Disease:  Alcohol dependence
Disease Ontology: DOID:0050741
OMIM: 103780
Drugs: 
Side effects:  Sedation and impairment of motor coordination at higher doses.
Therapeutic use:  KCa2 activators have been suggested for the treatment of alcohol dependence and other addictions
References:  27-29,40
Disease:  Alzheimer disease
Synonyms: Alzheimer's disease [Disease Ontology: DOID:10652]
Disease Ontology: DOID:10652
OMIM: 104300
Role: 
Drugs: 
Side effects:  High doses of apamin induce seizures and lead to Purkinje cell degeneration in the cerebellum.
Therapeutic use:  KCa2,2 blockers have been suggested as memory enhancers.
References:  6,15-16,24,37,39,54,66
Disease:  Atrial Fibrillation
Drugs: 
Side effects:  Tremor, ataxia and convulsions at higher NS8593 doses.
Therapeutic use:  Negative KCa2 channel gating modulators have been proposed for the treatment of atrial fibrillation.
References:  17,25,46
Disease:  Cerebellar ataxia
Disease Ontology: DOID:0050753
Role: 
Drugs: 
Side effects:  Sedation at higher doses. KCa2.2 activation could potentially impair memory.
Therapeutic use:  KCa activators have been proposed for the treatment of cerebellar ataxia.
References:  3,33,35,48,51-52
Disease:  Epilepsy
Drugs: 
Side effects:  Sedation and impairment of motor coordination at higher doses.
Therapeutic use:  KCa2 activators have been suggested as anticonvulsants.
References:  4,6,13,36,49
Disease:  Stroke, hemorrhagic
OMIM: 614519
Drugs: 
Side effects:  Sedation and impairment of motor coordination at higher doses.
Therapeutic use:  KCa2 activators have been suggested for the treatment of stroke.
References:  2,18,42
Biologically Significant Variants
Type:  Splice variant
Species:  Mouse
Description:  Western blots if brain membrane proteins prepared from wild-type and KCa2.2-null mice reveal two isoforms of KCa2.2, a 49kDa band corresponding to the previously reported protein (SK2-S; NP_536713) and a 78kDa isoform with an extended N-terminus with an additional 275aa (SK2-L; AK033158). SK2-L is funcktional and has similar Ca2+ sensitivity as SK2-S. It has a similar, though not idential, expression pattern, with lower levels overall. It is proposed to preferentially form heteromultimers with other KCa2 proteins.
Amino acids:  849
References:  59
Type:  Splice variant
Species:  Human
Description:  Shorter variant
Amino acids:  231
Nucleotide accession: 
Protein accession: 
Type:  Splice variant
Species:  Human
Description:  Longer variant
Amino acids:  579
Nucleotide accession: 
Protein accession: 
General Comments
Reviews of KCa2.2 channel physiology and pharmacology can be found in [1,55-56,66].

References

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1. Adelman JP, Maylie J, Sah P. (2012) Small-conductance Ca2+-activated K+ channels: form and function. Annu. Rev. Physiol.74: 245-69. [PMID:21942705]

2. Allen D, Nakayama S, Kuroiwa M, Nakano T, Palmateer J, Kosaka Y, Ballesteros C, Watanabe M, Bond CT, Luján R et al.. (2011) SK2 channels are neuroprotective for ischemia-induced neuronal cell death. J. Cereb. Blood Flow Metab.31 (12): 2302-12. [PMID:21712833]

3. Alviña K, Khodakhah K. (2010) KCa channels as therapeutic targets in episodic ataxia type-2. J. Neurosci.30 (21): 7249-57. [PMID:20505091]

4. Anderson NJ, Slough S, Watson WP. (2006) In vivo characterisation of the small-conductance KCa (SK) channel activator 1-ethyl-2-benzimidazolinone (1-EBIO) as a potential anticonvulsant. Eur. J. Pharmacol.546 (1-3): 48-53. [PMID:16925994]

5. Bildl W, Strassmaier T, Thurm H, Andersen J, Eble S, Oliver D, Knipper M, Mann M, Schulte U, Adelman JP et al.. (2004) Protein kinase CK2 is coassembled with small conductance Ca(2+)-activated K+ channels and regulates channel gating. Neuron43 (6): 847-58. [PMID:15363395]

6. 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]

7. Bond CT, Herson PS, Strassmaier T, Hammond R, Stackman R, Maylie J, Adelman JP. (2004) Small conductance Ca2+-activated K+ channel knock-out mice reveal the identity of calcium-dependent afterhyperpolarization currents. J. Neurosci.24 (23): 5301-6. [PMID:15190101]

8. Cao Y, Dreixler JC, Roizen JD, Roberts MT, Houamed KM. (2001) Modulation of recombinant small-conductance Ca(2+)-activated K(+) channels by the muscle relaxant chlorzoxazone and structurally related compounds. J. Pharmacol. Exp. Ther.296 (3): 683-9. [PMID:11181893]

9. Cao YJ, Dreixler JC, Couey JJ, Houamed KM. (2002) Modulation of recombinant and native neuronal SK channels by the neuroprotective drug riluzole. Eur. J. Pharmacol.449 (1-2): 47-54. [PMID:12163105]

10. 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]

11. 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]

12. Cingolani LA, Gymnopoulos M, Boccaccio A, Stocker M, Pedarzani P. (2002) Developmental regulation of small-conductance Ca2+-activated K+ channel expression and function in rat Purkinje neurons. J. Neurosci.22 (11): 4456-67. [PMID:12040053]

13. Coleman N, Nguyen HM, Cao Z, Brown BM, Jenkins DP, Zolkowska D, Chen YJ, Tanaka BS, Goldin AL, Rogawski MA et al.. (2015) The riluzole derivative 2-amino-6-trifluoromethylthio-benzothiazole (SKA-19), a mixed KCa2 activator and NaV blocker, is a potent novel anticonvulsant. Neurotherapeutics12 (1): 234-49. [PMID:25256961]

14. Desai R, Peretz A, Idelson H, Lazarovici P, Attali B. (2000) Ca2+-activated K+ channels in human leukemic Jurkat T cells. Molecular cloning, biochemical and functional characterization. J. Biol. Chem.275 (51): 39954-63. [PMID:10991935]

15. Deschaux O, Bizot JC. (2005) Apamin produces selective improvements of learning in rats. Neurosci. Lett.386 (1): 5-8. [PMID:15985330]

16. Deschaux O, Bizot JC, Goyffon M. (1997) Apamin improves learning in an object recognition task in rats. Neurosci. Lett.222 (3): 159-62. [PMID:9148239]

17. Diness JG, Skibsbye L, Jespersen T, Bartels ED, Sørensen US, Hansen RS, Grunnet M. (2011) Effects on atrial fibrillation in aged hypertensive rats by Ca(2+)-activated K(+) channel inhibition. Hypertension57 (6): 1129-35. [PMID:21502564]

18. Dolga AM, Terpolilli N, Kepura F, Nijholt IM, Knaus HG, D'Orsi B, Prehn JH, Eisel UL, Plant T, Plesnila N et al.. (2011) KCa2 channels activation prevents [Ca2+]i deregulation and reduces neuronal death following glutamate toxicity and cerebral ischemia. Cell Death Dis2: e147. [PMID:21509037]

19. Dreixler JC, Bian J, Cao Y, Roberts MT, Roizen JD, Houamed KM. (2000) Block of rat brain recombinant SK channels by tricyclic antidepressants and related compounds. Eur. J. Pharmacol.401 (1): 1-7. [PMID:10915830]

20. 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]

21. Feranchak AP, Doctor RB, Troetsch M, Brookman K, Johnson SM, Fitz JG. (2004) Calcium-dependent regulation of secretion in biliary epithelial cells: the role of apamin-sensitive SK channels. Gastroenterology127 (3): 903-13. [PMID:15362045]

22. 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]

23. Grissmer S, Lewis RS, Cahalan MD. (1992) Ca(2+)-activated K+ channels in human leukemic T cells. J. Gen. Physiol.99 (1): 63-84. [PMID:1371308]

24. Hammond RS, Bond CT, Strassmaier T, Ngo-Anh TJ, Adelman JP, Maylie J, Stackman RW. (2006) Small-conductance Ca2+-activated K+ channel type 2 (SK2) modulates hippocampal learning, memory, and synaptic plasticity. J. Neurosci.26 (6): 1844-53. [PMID:16467533]

25. Haugaard MM, Hesselkilde EZ, Pehrson S, Carstensen H, Flethøj M, Præstegaard KF, Sørensen US, Diness JG, Grunnet M, Buhl R et al.. (2015) Pharmacologic inhibition of small-conductance calcium-activated potassium (SK) channels by NS8593 reveals atrial antiarrhythmic potential in horses. Heart Rhythm12 (4): 825-35. [PMID:25542425]

26. Hirschberg B, Maylie J, Adelman JP, Marrion NV. (1998) Gating of recombinant small-conductance Ca-activated K+ channels by calcium. J. Gen. Physiol.111 (4): 565-81. [PMID:9524139]

27. Hopf FW, Bowers MS, Chang SJ, Chen BT, Martin M, Seif T, Cho SL, Tye K, Bonci A. (2010) Reduced nucleus accumbens SK channel activity enhances alcohol seeking during abstinence. Neuron65 (5): 682-94. [PMID:20223203]

28. Hopf FW, Seif T, Bonci A. (2011) The SK channel as a novel target for treating alcohol use disorders. Channels (Austin)5 (4): 289-92. [PMID:21712648]

29. Hopf FW, Simms JA, Chang SJ, Seif T, Bartlett SE, Bonci A. (2011) Chlorzoxazone, an SK-type potassium channel activator used in humans, reduces excessive alcohol intake in rats. Biol. Psychiatry69 (7): 618-24. [PMID:21195386]

30. 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]

31. Ishii TM, Maylie J, Adelman JP. (1997) Determinants of apamin and d-tubocurarine block in SK potassium channels. J. Biol. Chem.272 (37): 23195-200. [PMID:9287325]

32. Jäger H, Adelman JP, Grissmer S. (2000) SK2 encodes the apamin-sensitive Ca(2+)-activated K(+) channels in the human leukemic T cell line, Jurkat. FEBS Lett.469 (2-3): 196-202. [PMID:10713270]

33. 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]

34. Kohler M, Hirschberg B, Bond CT, Kinzie JM, Marrion NV, Maylie J, Adelman JP. (1996) Small-conductance, calcium-activated potassium channels from mammalian brain. Science273 (5282): 1709-14. [PMID:8781233]

35. 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. Targets17 (10): 1203-20. [PMID:23883298]

36. Lappin SC, Dale TJ, Brown JT, Trezise DJ, Davies CH. (2005) Activation of SK channels inhibits epileptiform bursting in hippocampal CA3 neurons. Brain Res.1065 (1-2): 37-46. [PMID:16336949]

37. Messier C, Mourre C, Bontempi B, Sif J, Lazdunski M, Destrade C. (1991) Effect of apamin, a toxin that inhibits Ca(2+)-dependent K+ channels, on learning and memory processes. Brain Res.551 (1-2): 322-6. [PMID:1913161]

38. Monaghan AS, Benton DC, Bahia PK, Hosseini R, Shah YA, Haylett DG, Moss GW. (2004) The SK3 subunit of small conductance Ca2+-activated K+ channels interacts with both SK1 and SK2 subunits in a heterologous expression system. J. Biol. Chem.279 (2): 1003-9. [PMID:14559917]

39. 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]

40. Mulholland PJ, Becker HC, Woodward JJ, Chandler LJ. (2011) Small conductance calcium-activated potassium type 2 channels regulate alcohol-associated plasticity of glutamatergic synapses. Biol. Psychiatry69 (7): 625-32. [PMID:21056409]

41. 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]

42. Orfila JE, Shimizu K, Garske AK, Deng G, Maylie J, Traystman RJ, Quillinan N, Adelman JP, Herson PS. (2014) Increasing small conductance Ca2+-activated potassium channel activity reverses ischemia-induced impairment of long-term potentiation. Eur. J. Neurosci.40 (8): 3179-88. [PMID:25080203]

43. 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]

44. Pedarzani P, McCutcheon JE, Rogge G, Jensen BS, Christophersen P, Hougaard C, Strøbaek D, Stocker M. (2005) Specific enhancement of SK channel activity selectively potentiates the afterhyperpolarizing current I(AHP) and modulates the firing properties of hippocampal pyramidal neurons. J. Biol. Chem.280 (50): 41404-11. [PMID:16239218]

45. Pedarzani P, Mosbacher J, Rivard A, Cingolani LA, Oliver D, Stocker M, Adelman JP, Fakler B. (2001) Control of electrical activity in central neurons by modulating the gating of small conductance Ca2+-activated K+ channels. J. Biol. Chem.276 (13): 9762-9. [PMID:11134030]

46. Qi XY, Diness JG, Brundel BJ, Zhou XB, Naud P, Wu CT, Huang H, Harada M, Aflaki M, Dobrev D et al.. (2014) Role of small-conductance calcium-activated potassium channels in atrial electrophysiology and fibrillation in the dog. Circulation129 (4): 430-40. [PMID:24190961]

47. 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]

48. Romano S, Coarelli G, Marcotulli C, Leonardi L, Piccolo F, Spadaro M, Frontali M, Ferraldeschi M, Vulpiani MC, Ponzelli F et al.. (2015) Riluzole in patients with hereditary cerebellar ataxia: a randomised, double-blind, placebo-controlled trial. Lancet Neurol14 (10): 985-91. [PMID:26321318]

49. 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]

50. Schumacher MA, Rivard AF, Bächinger HP, Adelman JP. (2001) Structure of the gating domain of a Ca2+-activated K+ channel complexed with Ca2+/calmodulin. Nature410 (6832): 1120-4. [PMID:11323678]

51. 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]

52. Shakkottai VG, do Carmo Costa M, Dell'Orco JM, Sankaranarayanan A, Wulff H, Paulson HL. (2011) Early changes in cerebellar physiology accompany motor dysfunction in the polyglutamine disease spinocerebellar ataxia type 3. J. Neurosci.31 (36): 13002-14. [PMID:21900579]

53. 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]

54. Stackman RW, Hammond RS, Linardatos E, Gerlach A, Maylie J, Adelman JP, Tzounopoulos T. (2002) Small conductance Ca2+-activated K+ channels modulate synaptic plasticity and memory encoding. J. Neurosci.22 (23): 10163-71. [PMID:12451117]

55. 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]

56. Stocker M, Hirzel K, D'hoedt D, Pedarzani P. (2004) Matching molecules to function: neuronal Ca2+-activated K+ channels and afterhyperpolarizations. Toxicon43 (8): 933-49. [PMID:15208027]

57. Stocker M, Krause M, Pedarzani P. (1999) An apamin-sensitive Ca2+-activated K+ current in hippocampal pyramidal neurons. Proc. Natl. Acad. Sci. U.S.A.96 (8): 4662-7. [PMID:10200319]

58. 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]

59. Strassmaier T, Bond CT, Sailer CA, Knaus HG, Maylie J, Adelman JP. (2005) A novel isoform of SK2 assembles with other SK subunits in mouse brain. J. Biol. Chem.280 (22): 21231-6. [PMID:15797870]

60. 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]

61. Strøbaek D, Jørgensen TD, Christophersen P, Ahring PK, Olesen SP. (2000) Pharmacological characterization of small-conductance Ca(2+)-activated K(+) channels stably expressed in HEK 293 cells. Br. J. Pharmacol.129 (5): 991-9. [PMID:10696100]

62. 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. Acta1665 (1-2): 1-5. [PMID:15471565]

63. Syme CA, Gerlach AC, Singh AK, Devor DC. (2000) Pharmacological activation of cloned intermediate- and small-conductance Ca(2+)-activated K(+) channels. Am. J. Physiol., Cell Physiol.278 (3): C570-81. [PMID:10712246]

64. Villalobos C, Shakkottai VG, Chandy KG, Michelhaugh SK, Andrade R. (2004) SKCa channels mediate the medium but not the slow calcium-activated afterhyperpolarization in cortical neurons. J. Neurosci.24 (14): 3537-42. [PMID:15071101]

65. 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]

66. 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]

67. 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]

68. 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. Nature395 (6701): 503-7. [PMID:9774106]

69. Xu Y, Tuteja D, Zhang Z, Xu D, Zhang Y, Rodriguez J, Nie L, Tuxson HR, Young JN, Glatter KA, Vázquez AE, Yamoah EN, Chiamvimonvat N. (2003) Molecular identification and functional roles of a Ca(2+)-activated K+ channel in human and mouse hearts. J. Biol. Chem.278 (49): 49085-94. [PMID:13679367]

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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: KCa2.2. Last modified on 17/01/2017. Accessed on 24/11/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=382.