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KNa1.2

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Target not currently curated in GtoImmuPdb

Target id: 386

Nomenclature: KNa1.2

Family: Calcium- and sodium-activated potassium channels (KCa, KNa)

Contents:

Gene and Protein Information Click here for help
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 0 1135 1q31.3 KCNT2 potassium sodium-activated channel subfamily T member 2 5,18
Mouse 6 0 1142 1F Kcnt2 potassium channel, subfamily T, member 2 18,22
Rat 6 0 1142 13q21 Kcnt2 potassium sodium-activated channel subfamily T member 2 5,13
Previous and Unofficial Names Click here for help
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 Click here for help
Alphafold Q6UVM3 (Hs), Q6UVM4 (Rn)
ChEMBL Target CHEMBL4739693 (Hs)
Ensembl Gene ENSG00000162687 (Hs), ENSMUSG00000052726 (Mm), ENSRNOG00000013312 (Rn)
Entrez Gene 343450 (Hs), 240776 (Mm), 304827 (Rn)
Human Protein Atlas ENSG00000162687 (Hs)
KEGG Gene hsa:343450 (Hs), mmu:240776 (Mm), rno:304827 (Rn)
OMIM 610044 (Hs)
Pharos Q6UVM3 (Hs)
RefSeq Nucleotide NM_198503 (Hs), NM_001081027 (Mm), NM_198762 (Rn)
RefSeq Protein NP_940905 (Hs), NP_001074496 (Mm), NP_942057 (Rn)
UniProtKB Q6UVM3 (Hs), Q6UVM4 (Rn)
Wikipedia KCNT2 (Hs)
Functional Characteristics Click here for help
KNa
Ion Selectivity and Conductance Click here for help
Species:  Rat
Rank order:  K+ [- pS] = K+ [- pS]
References:  1,21
Species:  Rat
Single channel conductance (pS):  59 (80mM symmetric K+)
References:  21
Species:  Rat
Single channel conductance (pS):  141.0 (130 mM symmetric K+)
References:  1
Voltage Dependence Click here for help
  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 - 21 Xenopus laevis Oocytes Rat
Inactivation  - - 21
Comments  Low intrinsic voltage-sensitivity

Download all structure-activity data for this target as a CSV file go icon to follow link

Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
Cl- Click here for species-specific activity table Ligand is endogenous in the given species Rn Agonist - - 3x10-3 - 1.3x10-1 - 1
⤷ Conc range: 3x10-3 - 1.3x10-1 M [1]
Na+ Click here for species-specific activity table Ligand is endogenous in the given species Rn Agonist - - 1x10-3 - 1x10-1 - 1
⤷ Conc range: 1x10-3 - 1x10-1 M [1]
flufenamic acid Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Agonist 8.9 pEC50 - - 6,12
⤷ pEC50 8.9 (EC50 1.4x10-9 M) [6,12]
niflumic acid Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand 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 Click here for help
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
ATP Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Rn - - - < 5x10-3 - 1
⤷ Conc range: < 5x10-3 M [1]
phorbol 12-myristate 13-acetate Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.9 pIC50 - - 21
⤷ pIC50 7.9 [21]
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 Value Parameter Concentration range (M) Holding voltage (mV) Reference
tetraethylammonium Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition - - 7x10-2 - 1.5x10-1 - 21
⤷ Conc range: 7x10-2 - 1.5x10-1 M [21]
tetraethylammonium Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Rn Inhibition - - 1x10-3 - 2x10-2 - 21
⤷ Conc range: 1x10-3 - 2x10-2 M [21]
quinidine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Guide to Malaria Pharmacology Ligand Rn Inhibition - - 1x10-3 - 1
⤷ Conc range: 1x10-3 M [1]
clofilium Small molecule or natural product Click here for species-specific activity table Hs Antagonist - - 1.09x10-4 - 7
⤷ Conc range: 1.09x10-4 M [7]
Ba2+ Click here for species-specific activity table Hs Inhibition 3.0 pIC50 - - 1
⤷ pIC50 3.0 [1]
View species-specific channel blocker tables
Tissue Distribution Click here for help
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 [9-10,14,17,19-20,24] 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 [23], 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 et al.. (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. Mouse Genome Sequencing Consortium, Waterston RH, Lindblad-Toh K, Birney E, Rogers J, Abril JF, Agarwal P, Agarwala R, Ainscough R, Alexandersson M et al.. (2002) Initial sequencing and comparative analysis of the mouse genome. Nature, 420 (6915): 520-62. [PMID:12466850]

19. 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]

20. 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]

21. 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]

22. 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 USA, 99 (26): 16899-903. [PMID:12477932]

23. 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]

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]

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