K<sub>Na</sub>1.2 | Calcium- and sodium-activated potassium channels | IUPHAR/BPS Guide to PHARMACOLOGY

KNa1.2

Target id: 386

Nomenclature: KNa1.2

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 KNa1.2 in GtoImmuPdb

Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 0 1138 1q31.3 KCNT2 potassium sodium-activated channel subfamily T member 2 5,23
Mouse 6 0 1142 1F Kcnt2 potassium channel, subfamily T, member 2 21,23
Rat 6 0 1142 13q13 Kcnt2 potassium sodium-activated channel subfamily T member 2 5,13
Previous and Unofficial Names
KCa4.2 | sodium and chloride-activated ATP-sensitive potassium channel | Slick | Slo2.1 | potassium channel, sodium activated subfamily T, member 2 | potassium channel, sodium-activated subfamily T, member 2 | potassium channel
Database Links
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Functional Characteristics
KNa
Ion Selectivity and Conductance
Species:  Rat
Rank order:  K+ [- pS] = K+ [- pS]
References:  1,20
Species:  Rat
Single channel conductance (pS):  59 (80mM symmetric K+)
References:  20
Species:  Rat
Single channel conductance (pS):  141.0 (130 mM symmetric K+)
References:  1
Voltage Dependence
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  - - 1 CHO cells. Rat
Inactivation  - -
Comments  Weak voltage-dependence
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -23.0 - 20 Xenopus laevis Oocytes Rat
Inactivation  - - 20
Comments  Low intrinsic voltage-sensitivity

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
Cl- Rn Agonist - - 3x10-3 - 1.3x10-1 - 1
Conc range: 3x10-3 - 1.3x10-1 M [1]
Na+ Rn Agonist - - 1x10-3 - 1x10-1 - 1
Conc range: 1x10-3 - 1x10-1 M [1]
flufenamic acid Hs Agonist 8.9 pEC50 - - 6,12
pEC50 8.9 (EC50 1.4x10-9 M) [6,12]
niflumic acid Hs Agonist 8.7 pEC50 - - 6,12
pEC50 8.7 (EC50 2.1x10-9 M) [6,12]
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+. [1]
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 - 1
Conc range: < 5x10-3 M [1]
phorbol 12-myristate 13-acetate Hs Inhibition 7.9 pIC50 - - 20
pIC50 7.9 [20]
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 - 20
Conc range: 7x10-2 - 1.5x10-1 M [20]
tetraethylammonium Rn Inhibition - - 1x10-3 - 2x10-2 - 20
Conc range: 1x10-3 - 2x10-2 M [20]
quinidine Rn Inhibition - - 1x10-3 - 1
Conc range: 1x10-3 M [1]
clofilium Hs Antagonist - - 1.09x10-4 - 7
Conc range: 1.09x10-4 M [7]
Ba2+ Hs Inhibition 3.0 pIC50 - - 1
pIC50 3.0 [1]
View species-specific channel blocker tables
Tissue Distribution
Ubiquitous (brain, heart, skeletal muscle, kidney, testis, lung, liver)
Species:  Mouse
Technique:  RT-PCR
References:  25
Brain, heart (weak)
Species:  Rat
Technique:  Northern Blot
References:  1
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:  2
General Comments
KCNT1 and KCNT2 likely encode native KNa channels [8,15,25]. Native KNa channels were first recorded from guinea pig cardiac myocytes [16], then later found widely in neurons in the vertebrate central nervous system [9-10,14,17-19,24] and dorsal root ganglia [3]. KNa1.2 channels can form heteromultimers with the Slack-B isoform of KNa1.1 channels [4]. KNa1.2 channels are more widely distributed than KNa1.1 channels. They are also more sensitive to Cl- and slightly less sensitive to Na+ than KNa1.1 [1]. The primary residue allowing regulation of KNa1.2 channels by intracellular Na+ is Asp757 in the cytoplasmic C-terminal domain [22], which is allosterically coupled to channel activation [11].

References

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1. 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]

2. 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]

3. 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]

4. Chen H, Kronengold J, Yan Y, Gazula VR, Brown MR, Ma L, Ferreira G, Yang Y, Bhattacharjee A, Sigworth FJ et al.. (2009) The N-terminal domain of Slack determines the formation and trafficking of Slick/Slack heteromeric sodium-activated potassium channels. J. Neurosci., 29 (17): 5654-65. [PMID:19403831]

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. Neuron, 49 (3): 409-20. [PMID:16446144]

6. Dai L, Garg V, Sanguinetti MC. (2010) Activation of Slo2.1 channels by niflumic acid. J. Gen. Physiol., 135 (3): 275-95. [PMID:20176855]

7. de Los Angeles Tejada M, Stolpe K, Meinild AK, Klaerke DA. (2012) Clofilium inhibits Slick and Slack potassium channels. Biologics, 6: 465-70. [PMID:23271893]

8. Dryer SE. (2003) Molecular identification of the Na+-activated K+ channel. Neuron, 37 (5): 727-8. [PMID:12628162]

9. 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]

10. 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]

11. Garg P, Gardner A, Garg V, Sanguinetti MC. (2013) Structural basis of ion permeation gating in Slo2.1 K+ channels. J. Gen. Physiol., 142 (5): 523-42. [PMID:24166878]

12. Garg P, Sanguinetti MC. (2012) Structure-activity relationship of fenamates as Slo2.1 channel activators. Mol. Pharmacol., 82 (5): 795-802. [PMID:22851714]

13. 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. Nature, 428 (6982): 493-521. [PMID:15057822]

14. 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]

15. Kaczmarek LK. (2013) Slack, Slick and Sodium-Activated Potassium Channels. ISRN Neurosci, 2013 (2013). [PMID:24319675]

16. Kameyama M, Kakei M, Sato R, Shibasaki T, Matsuda H, Irisawa H. (1984) Intracellular Na+ activates a K+ channel in mammalian cardiac cells. Nature, 309 (5966): 354-6. [PMID:6328309]

17. 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]

18. 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]

19. 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]

20. 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]

21. 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]

22. Thomson SJ, Hansen A, Sanguinetti MC. (2015) Identification of the Intracellular Na+ Sensor in Slo2.1 Potassium Channels. J. Biol. Chem., 290 (23): 14528-35. [PMID:25903137]

23. 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. Nature, 420 (6915): 520-62. [PMID:12466850]

24. 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]

25. 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. Neuron, 37 (5): 765-73. [PMID:12628167]

Contributors

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How to cite this page

Richard Aldrich, K. George Chandy, Stephan Grissmer, George A. Gutman, Aguan D. Wei, Heike Wulff.
Calcium- and sodium-activated potassium channels: KNa1.2. Last modified on 06/09/2016. Accessed on 18/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=386.