Nomenclature: KCa4.2

Family: Calcium-activated potassium channels

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

Contents

Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 0 1138 1q31.3 KCNT2 potassium channel, subfamily T, member 2 5,17
Mouse 6 0 1142 1F Kcnt2 potassium channel, subfamily T, member 2 16-17
Rat 6 0 1142 13q13 Kcnt2 potassium channel, subfamily T, member 2 5,9
Previous and Unofficial Names
Slick
Slo2.1
KCNT2
KCa4.2
SLICK
SLO2.1
sodium and chloride activated ATP sensitive potassium channel
potassium channel subfamily T member 2
potassium channel, subfamily T, member 2
sequence like an intermediate conductance potassium channel subunit
sodium and chloride-activated ATP-sensitive potassium channel Slo2.1
sodium- and chloride-activated ATP-sensitive potassium channel
E330038N15Rik
Database Links
Ensembl Gene
Entrez Gene
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
OMIM
PharmGKB Gene
PhosphoSitePlus
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene Hs.
UniProtKB
Wikipedia
Functional Characteristics
Maxi KCa KNa (slack & slick)
Ion Selectivity and Conductance
Species:  Human
Rank order:  K+ [- pS] = K+ [- pS]
References:  2,15
Species:  Human
Single channel conductance (pS):  59 (80mM symmetric K+)
References:  15
Species:  Human
Single channel conductance (pS):  141.0 (130 mM symmetric K+)
References:  2
Voltage Dependence
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  - - 2 CHO cells. Human
Inactivation  - -
Comments  Weak voltage-dependence
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -23.0 - 15 Xenopus laevis Oocytes Human
Inactivation  - - 15
Comments  Low intrinsic voltage-sensitivity
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
Cl- Rn Agonist - - 3x10-3 - 1.3x10-1 - 2
Conc range: 3x10-3 - 1.3x10-1 M [2]
Na+ Rn Agonist - - 1x10-3 - 1x10-1 - 2
Conc range: 1x10-3 - 1x10-1 M [2]
NS004 Hs - - - - -
NS1619 Hs - - - - -
View species-specific activator tables
Activator Comments
Cytoplasmic Na+; 5-fold increase in NPo from 1-100mM Na+, with 30mM Cl- and Cytoplasmic Cl-; 5-fold increase in NPo from 3-130mM Cl-, with 5 mM Na+. [2]
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
ATP Rn - - - < 5x10-3 - 2
Conc range: < 5x10-3 M [2]
phorbol 12-myristate 13-acetate Hs Inhibition 7.92 pIC50 - - 15
pIC50 7.92 [15]
View species-specific gating inhibitor tables
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
tetraethylammonium Hs Inhibition - - 7x10-2 - 1.5x10-1 - 15
Conc range: 7x10-2 - 1.5x10-1 M [15]
quinidine Rn Inhibition - - 1x10-3 - 2
Conc range: 1x10-3 M [2]
Ba2+ Hs Inhibition 3.0 pIC50 - - 2
pIC50 3.0 [2]
View species-specific channel blocker tables
Tissue Distribution
Ubiquitous (brain, heart, skeletal muscle, kidney, testis, lung, liver)
Species:  Mouse
Technique:  RT-PCR
References:  19
Brain, heart (weak)
Species:  Rat
Technique:  Northern Blot
References:  2
Brain (olfactory bulb, supraoptic nucleus, hippocampus, somatosensory and visual cortex, thalamus, deep cerebellar nucleus, ocularmotor nucleus, auditory nuclei). Neuronal immunohistochemical staining observed in cell bodies and axonal tracts. Immunohistochemical staining corroborated by in situ hybridizations.
Species:  Rat
Technique:  Immunohistochemistry
References:  3
General Comments
KCNT1 and KCNT2 likely encode native KNa channels [1,6,19]. Native KNa channels were first recorded from guinea pig cardiac myocytes [11], then later found widely in neurons in the vertebrate central nervous system [7-8,10,12-14,18] and dorsal root ganglia [4]. KNa channels have been proposed to protect against hypoxic insult [11], but this and other possible functions remain to be clearly established. Interestingly, C. elegans slo-2 loss-of-function mutants are hypersensitive to hypoxic death [19].

REFERENCES

1. 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]

2. Bhattacharjee A, Joiner WJ, Wu M, Yang Y, Sigworth FJ, Kaczmarek LK. (2003) Slick (Slo2.1), a rapidly-gating sodium-activated potassium channel inhibited by ATP. J. Neurosci.23 (37): 11681-91. [PMID:14684870]

3. Bhattacharjee A, von Hehn CA, Mei X, Kaczmarek LK. (2005) Localization of the Na+-activated K+ channel Slick in the rat central nervous system. J. Comp. Neurol.484 (1): 80-92. [PMID:15717307]

4. Bischoff U, Vogel W, Safronov BV. (1998) Na+-activated K+ channels in small dorsal root ganglion neurones of rat. J. Physiol. (Lond.)510 ( Pt 3): 743-54. [PMID:9660890]

5. Chen Y, Yu FH, Surmeier DJ, Scheuer T, Catterall WA. (2006) Neuromodulation of Na+ channel slow inactivation via cAMP-dependent protein kinase and protein kinase C. Neuron49 (3): 409-20. [PMID:16446144]

6. Dryer SE. (2003) Molecular identification of the Na+-activated K+ channel. Neuron37 (5): 727-8. [PMID:12628162]

7. Egan TM, Dagan D, Kupper J, Levitan IB. (1992) Na(+)-activated K+ channels are widely distributed in rat CNS and in Xenopus oocytes. Brain Res.584 (1-2): 319-21. [PMID:1515948]

8. Egan TM, Dagan D, Kupper J, Levitan IB. (1992) Properties and rundown of sodium-activated potassium channels in rat olfactory bulb neurons. J. Neurosci.12 (5): 1964-76. [PMID:1578280]

9. Gibbs RA, Weinstock GM, Metzker ML, Muzny DM, Sodergren EJ, Scherer S, Scott G, Steffen D, Worley KC, Burch PE, Okwuonu G, Hines S, Lewis L, DeRamo C, Delgado O, Dugan-Rocha S, Miner G, Morgan M, Hawes A, Gill R, Celera RA, Adams MD, Amanatides PG, Baden-Tillson H, Barnstead M, Chin S, Evans CA, Ferriera S, Fosler C, Glodek A, Gu Z, Jennings D, Kraft CL, Nguyen T, Pfannkoch CM, Sitter C, Sutton GG, Venter JC, Woodage T, Smith D, Lee HM, Gustafson E, Cahill P, Kana A, Doucette-Stamm L, Weinstock K, Fechtel K, Weiss RB, Dunn DM, Green ED, Blakesley RW, Bouffard GG, De Jong PJ, Osoegawa K, Zhu B, Marra M, Schein J, Bosdet I, Fjell C, Jones S, Krzywinski M, Mathewson C, Siddiqui A, Wye N, McPherson J, Zhao S, Fraser CM, Shetty J, Shatsman S, Geer K, Chen Y, Abramzon S, Nierman WC, Havlak PH, Chen R, Durbin KJ, Egan A, Ren Y, Song XZ, Li B, Liu Y, Qin X, Cawley S, Worley KC, Cooney AJ, D'Souza LM, Martin K, Wu JQ, Gonzalez-Garay ML, Jackson AR, Kalafus KJ, McLeod MP, Milosavljevic A, Virk D, Volkov A, Wheeler DA, Zhang Z, Bailey JA, Eichler EE, Tuzun E, Birney E, Mongin E, Ureta-Vidal A, Woodwark C, Zdobnov E, Bork P, Suyama M, Torrents D, Alexandersson M, Trask BJ, Young JM, Huang H, Wang H, Xing H, Daniels S, Gietzen D, Schmidt J, Stevens K, Vitt U, Wingrove J, Camara F, Mar Albà M, Abril JF, Guigo R, Smit A, Dubchak I, Rubin EM, Couronne O, Poliakov A, Hübner N, Ganten D, Goesele C, Hummel O, Kreitler T, Lee YA, Monti J, Schulz H, Zimdahl H, Himmelbauer H, Lehrach H, Jacob HJ, Bromberg S, Gullings-Handley J, Jensen-Seaman MI, Kwitek AE, Lazar J, Pasko D, Tonellato PJ, Twigger S, Ponting CP, Duarte JM, Rice S, Goodstadt L, Beatson SA, Emes RD, Winter EE, Webber C, Brandt P, Nyakatura G, Adetobi M, Chiaromonte F, Elnitski L, Eswara P, Hardison RC, Hou M, Kolbe D, Makova K, Miller W, Nekrutenko A, Riemer C, Schwartz S, Taylor J, Yang S, Zhang Y, Lindpaintner K, Andrews TD, Caccamo M, Clamp M, Clarke L, Curwen V, Durbin R, Eyras E, Searle SM, Cooper GM, Batzoglou S, Brudno M, Sidow A, Stone EA, Venter JC, Payseur BA, Bourque G, López-Otín C, Puente XS, Chakrabarti K, Chatterji S, Dewey C, Pachter L, Bray N, Yap VB, Caspi A, Tesler G, Pevzner PA, Haussler D, Roskin KM, Baertsch R, Clawson H, Furey TS, Hinrichs AS, Karolchik D, Kent WJ, Rosenbloom KR, Trumbower H, Weirauch M, Cooper DN, Stenson PD, Ma B, Brent M, Arumugam M, Shteynberg D, Copley RR, Taylor MS, Riethman H, Mudunuri U, Peterson J, Guyer M, Felsenfeld A, Old S, Mockrin S, Collins F. (2004) Genome sequence of the Brown Norway rat yields insights into mammalian evolution. Nature428 (6982): 493-521. [PMID:15057822]

10. Hess D, Nanou E, El Manira A. (2007) Characterization of Na+-activated K+ currents in larval lamprey spinal cord neurons. J. Neurophysiol.97 (5): 3484-93. [PMID:17329626]

11. Kameyama M, Kakei M, Sato R, Shibasaki T, Matsuda H, Irisawa H. (1984) Intracellular Na+ activates a K+ channel in mammalian cardiac cells. Nature309 (5966): 354-6. [PMID:6328309]

12. Koh DS, Jonas P, Vogel W. (1994) Na(+)-activated K+ channels localized in the nodal region of myelinated axons of Xenopus. J. Physiol. (Lond.)479 ( Pt 2): 183-97. [PMID:7799220]

13. Nanou E, El Manira A. (2007) A postsynaptic negative feedback mediated by coupling between AMPA receptors and Na+-activated K+ channels in spinal cord neurones. Eur. J. Neurosci.25 (2): 445-50. [PMID:17284185]

14. Safronov BV, Vogel W. (1996) Properties and functions of Na(+)-activated K+ channels in the soma of rat motoneurones. J. Physiol. (Lond.)497 ( Pt 3): 727-34. [PMID:9003557]

15. Santi CM, Ferreira G, Yang B, Gazula VR, Butler A, Wei A, Kaczmarek LK, Salkoff L. (2006) Opposite regulation of Slick and Slack K+ channels by neuromodulators. J. Neurosci.26 (19): 5059-68. [PMID:16687497]

16. Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS, Wagner L, Shenmen CM, Schuler GD, Altschul SF et al.. (2002) Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proc. Natl. Acad. Sci. U.S.A.99 (26): 16899-903. [PMID:12477932]

17. Waterston RH, Lindblad-Toh K, Birney E, Rogers J, Abril JF, Agarwal P, Agarwala R, Ainscough R, Alexandersson M, An P, Antonarakis SE, Attwood J, Baertsch R, Bailey J, Barlow K, Beck S, Berry E, Birren B, Bloom T, Bork P, Botcherby M, Bray N, Brent MR, Brown DG, Brown SD, Bult C, Burton J, Butler J, Campbell RD, Carninci P, Cawley S, Chiaromonte F, Chinwalla AT, Church DM, Clamp M, Clee C, Collins FS, Cook LL, Copley RR, Coulson A, Couronne O, Cuff J, Curwen V, Cutts T, Daly M, David R, Davies J, Delehaunty KD, Deri J, Dermitzakis ET, Dewey C, Dickens NJ, Diekhans M, Dodge S, Dubchak I, Dunn DM, Eddy SR, Elnitski L, Emes RD, Eswara P, Eyras E, Felsenfeld A, Fewell GA, Flicek P, Foley K, Frankel WN, Fulton LA, Fulton RS, Furey TS, Gage D, Gibbs RA, Glusman G, Gnerre S, Goldman N, Goodstadt L, Grafham D, Graves TA, Green ED, Gregory S, Guigó R, Guyer M, Hardison RC, Haussler D, Hayashizaki Y, Hillier LW, Hinrichs A, Hlavina W, Holzer T, Hsu F, Hua A, Hubbard T, Hunt A, Jackson I, Jaffe DB, Johnson LS, Jones M, Jones TA, Joy A, Kamal M, Karlsson EK, Karolchik D, Kasprzyk A, Kawai J, Keibler E, Kells C, Kent WJ, Kirby A, Kolbe DL, Korf I, Kucherlapati RS, Kulbokas EJ, Kulp D, Landers T, Leger JP, Leonard S, Letunic I, Levine R, Li J, Li M, Lloyd C, Lucas S, Ma B, Maglott DR, Mardis ER, Matthews L, Mauceli E, Mayer JH, McCarthy M, McCombie WR, McLaren S, McLay K, McPherson JD, Meldrim J, Meredith B, Mesirov JP, Miller W, Miner TL, Mongin E, Montgomery KT, Morgan M, Mott R, Mullikin JC, Muzny DM, Nash WE, Nelson JO, Nhan MN, Nicol R, Ning Z, Nusbaum C, O'Connor MJ, Okazaki Y, Oliver K, Overton-Larty E, Pachter L, Parra G, Pepin KH, Peterson J, Pevzner P, Plumb R, Pohl CS, Poliakov A, Ponce TC, Ponting CP, Potter S, Quail M, Reymond A, Roe BA, Roskin KM, Rubin EM, Rust AG, Santos R, Sapojnikov V, Schultz B, Schultz J, Schwartz MS, Schwartz S, Scott C, Seaman S, Searle S, Sharpe T, Sheridan A, Shownkeen R, Sims S, Singer JB, Slater G, Smit A, Smith DR, Spencer B, Stabenau A, Stange-Thomann N, Sugnet C, Suyama M, Tesler G, Thompson J, Torrents D, Trevaskis E, Tromp J, Ucla C, Ureta-Vidal A, Vinson JP, Von Niederhausern AC, Wade CM, Wall M, Weber RJ, Weiss RB, Wendl MC, West AP, Wetterstrand K, Wheeler R, Whelan S, Wierzbowski J, Willey D, Williams S, Wilson RK, Winter E, Worley KC, Wyman D, Yang S, Yang SP, Zdobnov EM, Zody MC, Lander ES. (2002) Initial sequencing and comparative analysis of the mouse genome. Nature420 (6915): 520-62. [PMID:12466850]

18. Yang B, Desai R, Kaczmarek LK. (2007) Slack and Slick K(Na) channels regulate the accuracy of timing of auditory neurons. J. Neurosci.27 (10): 2617-27. [PMID:17344399]

19. Yuan A, Santi CM, Wei A, Wang ZW, Pollak K, Nonet M, Kaczmarek L, Crowder CM, Salkoff L. (2003) The sodium-activated potassium channel is encoded by a member of the Slo gene family. Neuron37 (5): 765-73. [PMID:12628167]

To cite this database page, please use the following:

Richard Aldrich, K. George Chandy, Stephan Grissmer, George A. Gutman, Aguan D. Wei, Heike Wulff.
Calcium-activated potassium channels: KCa4.2. Last modified on 11/02/2014. Accessed on 01/08/2014. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=386.

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