Nomenclature: KCa4.1

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 1256 9q34.3 KCNT1 potassium channel, subfamily T, member 1 18
Mouse 6 0 1238 2 A3 Kcnt1 potassium channel, subfamily T, member 1 14,18,20
Rat 6 0 1237 3p13 Kcnt1 potassium channel, subfamily T, member 1 8,10
Previous and Unofficial Names
Slack
Slo2.2
KCNT1
KCa4.1
KIAA1422
Slack
rSlo2
potassium channel subfamily T member 1
potassium channel subunit (Slack)
potassium channel, subfamily T, member 1
sequence like a calcium-activated potassium channel subunit
slo2
C030030G16Rik
Database Links
Ensembl Gene
Entrez Gene
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
OMIM
Orphanet Gene
PharmGKB Gene
PhosphoSitePlus
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene Hs.
UniProtKB
Wikipedia
Associated Proteins
Heteromeric Pore-forming Subunits
Name References
Not determined
Auxiliary Subunits
Name References
PSD-95 19
Slo1 10
KCa1.1 10
Other Associated Proteins
Name References
Not determined
Functional Characteristics
Maxi KCa KNa (slack & slick)
Ion Selectivity and Conductance
Species:  Mouse
Rank order:  K+ > Na+ [5.0 pS]
References:  15,23
Species:  Rat
Rank order:  K+
References:  10
Species:  Rat
Macroscopic current rectification:  Inward
References:  10
Species:  Mouse
Macroscopic current rectification:  Inward
References:  15
Species:  Mouse
Macroscopic current rectification:  Inward
References:  23
Voltage Dependence Comments
Experiment in Xenopus ooctyes showed weak voltage-sensitivity [23]
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
Na+ Rn Agonist - - 1.5x10-2 - 23
Conc range: 1.5x10-2 M [23]
Cl- Rn Agonist - - 8x10-3 - 23
Conc range: 8x10-3 M [23]
phorbol 12-myristate 13-acetate Rn Agonist 7.0 – 7.3 pEC50 - - 17
pEC50 7.0 – 7.3 [17]
bithionol Rn Agonist 5.0 – 6.0 pEC50 - - 22
pEC50 5.0 – 6.0 [22]
NS004 Hs - - - - -
NS1619 Hs - - - - -
View species-specific activator tables
Activator Comments
Cytoplasmic Na+ works synergistically with Cl- for activation
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
Ca2+ Rn Antagonist - - 0x100 - 3x10-6 - 10
Conc range: 0x100 - 3x10-6 M [10]
Ca2+ Mm Antagonist 6.52 pIC50 - - 15
pIC50 6.52 [15]
bepridil Rn Antagonist 5.0 – 6.0 pIC50 - - 1,22
pIC50 5.0 – 6.0 [1,22]
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
quinidine Rn Antagonist 4.04 pIC50 - - 22
pIC50 4.04 [22]
tetraethylammonium Rn Antagonist 1.7 – 2.0 pIC50 - - 3
pIC50 1.7 – 2.0 [3]
Tissue Distribution
Kidney (covering the medullary and cortical thick ascending limbs of Henle’s loop)
Species:  Mouse
Technique:  RT-PCR
References:  15
Brain, Testis, Kidney
Species:  Mouse
Technique:  RT-PCR
References:  23
Brain:brainstem (red nucleus,oculomotor nucleus, mesencephalic trigeminal, trapezoid nucleus, gigantocellularius, vestibular nucleus), olfactory bulb, frontal cortex, hippocampus. Neuronal immunostaining observed in cell bodies and axonal tracts
Species:  Rat
Technique:  Immunohistochemistry
References:  2
Physiological Functions
KCNT1 is proposed to assist apical absorption of Na+ and Cl- in transport epithelium, by providing a basolateral hyperpolarizing potential, linked to increases in intracellular Na+ and Cl-.
Species:  Mouse
Tissue:  Kidney (medullary and cortical thick ascending limbs of Henle’s loop)
References:  15
KCNT1 channels are proposed to mediate a fast Na+-dependent component of after-hyperpolarizations in MNTB neurons. This permits these neurons to follow high frequency auditory input by triggering action potentials with high fidelity and precision.
Species:  Mouse
Tissue:  Medial nucleus of the trapezoid body (MNTB) in the auditory brainstem
References:  23
Clinically-Relevant Mutations and Pathophysiology
Disease:  Epilepsy, nocturnal frontal lobe, 5
OMIM:  615005
Orphanet:  98784
References: 
Mutations not determined
Disease:  Epileptic encephalopathy, early infantile, 14
OMIM:  614959
Orphanet:  293181
References: 
Mutations not determined
General Comments
KCNT1 and KCNT2 likely encode native KNa channels [1,5,23]. Native KNa channels were first recorded from guinea pig cardiac myocytes [11], then later found widely in neurons in the vertebrate central nervous system [6-7,9,12-13,16,21] 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 [23].

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, Gan L, Kaczmarek LK. (2002) Localization of the Slack potassium channel in the rat central nervous system. J. Comp. Neurol.454 (3): 241-54. [PMID:12442315]

3. Bhattacharjee A, Kaczmarek LK. (2005) For K+ channels, Na+ is the new Ca2+. Trends Neurosci.28 (8): 422-8. [PMID:15979166]

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

6. 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]

7. 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]

8. 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]

9. 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]

10. Joiner WJ, Tang MD, Wang LY, Dworetzky SI, Boissard CG, Gan L, Gribkoff VK, Kaczmarek LK. (1998) Formation of intermediate-conductance calcium-activated potassium channels by interaction of Slack and Slo subunits. Nat. Neurosci.1 (6): 462-9. [PMID:10196543]

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. Okazaki N, Kikuno R, Ohara R, Inamoto S, Koseki H, Hiraoka S, Saga Y, Nagase T, Ohara O, Koga H. (2003) Prediction of the coding sequences of mouse homologues of KIAA gene: III. the complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries. DNA Res.10 (4): 167-80. [PMID:14621295]

15. Paulais M, Lachheb S, Teulon J. (2006) A Na+- and Cl- -activated K+ channel in the thick ascending limb of mouse kidney. J. Gen. Physiol.127 (2): 205-15. [PMID:16446508]

16. 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]

17. 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]

18. 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]

19. Uchino S, Wada H, Honda S, Hirasawa T, Yanai S, Nakamura Y, Ondo Y, Kohsaka S. (2003) Slo2 sodium-activated K+ channels bind to the PDZ domain of PSD-95. Biochem. Biophys. Res. Commun.310 (4): 1140-7. [PMID:14559234]

20. 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]

21. 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]

22. Yang B, Gribkoff VK, Pan J, Damagnez V, Dworetzky SI, Boissard CG, Bhattacharjee A, Yan Y, Sigworth FJ, Kaczmarek LK. (2006) Pharmacological activation and inhibition of Slack (Slo2.2) channels. Neuropharmacology51 (4): 896-906. [PMID:16876206]

23. 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: KCa4.1. Last modified on 17/03/2014. Accessed on 21/10/2014. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=385.

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