KCa1.1

Target id: 380

Nomenclature: KCa1.1

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.  » Email us

Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 1 1182 10q22.3 KCNMA1 potassium calcium-activated channel subfamily M alpha 1 14
Mouse 6 1 1236 14 A3 Kcnma1 potassium large conductance calcium-activated channel, subfamily M, alpha member 1
Rat 6 1 1243 15p16 Kcnma1 potassium calcium-activated channel subfamily M alpha 1
Previous and Unofficial Names
BK channel
maxi K+ channel
BK channel alpha subunit
calcium-activated potassium channel alpha subunit
maxi K channel
slo-alpha
slowpoke homolog
potassium channel, calcium activated large conductance subfamily M alpha, member 1
Database Links
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
InterPro
KEGG Gene
NeXtProt
OMIM
Orphanet
PharmGKB Gene
PhosphoSitePlus
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniProtKB
Wikipedia
Associated Proteins
Heteromeric Pore-forming Subunits
Name References
Slack 7
Auxiliary Subunits
Name References
β1 - β4 1,6,17
γ1 - γ4 20-21
Other Associated Proteins
Name References
β2-adrenoceptor 9
Functional Characteristics
Maxi KCa
Ion Selectivity and Conductance
Species:  Human
Rank order:  K+ [200.0 - 220.0 pS]
References:  10,14
Species:  Mouse
Rank order:  K+ [272.0 pS]
References:  2,16

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
flindokalner Hs - 6.5 pEC50 - -100.0 5
pEC50 6.5 [5]
Holding voltage: -100.0 mV
17β-estradiol Hs - 5.6 pEC50 - - 15
pEC50 5.6 [15]
NS1643 Hs Agonist 5.2 – 5.7 pEC50 - -150.0 13
pEC50 5.2 – 5.7 [13]
Holding voltage: -150.0 mV
NS004 Hs - - - - -
NS1619 Hs - - - - -
Activator Comments
Mg2+ has also been reported as an activator for the KCa1.1
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
paxilline Mm - 8.7 pKi - 0.0 12
pKi 8.7 (Ki 1.9x10-9 M) [12]
Holding voltage: 0.0 mV
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
slotoxin Hs Antagonist 8.8 pKd - 0.0 4
pKd 8.8 [4]
Holding voltage: 0.0 mV
toxin BmP09 Rn - 7.6 pEC50 - 0.0 22
pEC50 7.6 [22]
Holding voltage: 0.0 mV
charybdotoxin Hs - - - - -
tetraethylammonium Hs - - - - -
iberiotoxin Hs - - - - -
View species-specific channel blocker tables
Channel Blocker Comments
Other channel blockers include: charybdotoxin, iberiotoxin and tetraethylammonium.
Tissue Distribution
Brain:-
basal nuclei (claustrum)
Expression level:  High
Species:  Rat
Technique:  in situ hybridisation
References:  11,18
Brain:-
neocortex (layer V/VI), pyriform cortex, septum (bed nucleus of the stria terminalis, lateral septum), thalamus (rhomboid nucleus)
Expression level:  Medium
Species:  Rat
Technique:  in situ hybridisation
References:  11,18
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Kcnma1tm1Ruth Kcnma1tm1Ruth/Kcnma1tm1Ruth
129-Kcnma1
MGI:99923  MP:0004746 abnormal cochlear IHC afferent innervation pattern PMID: 16763026 
Kcnma1tm1Rwa Kcnma1tm1Rwa/Kcnma1tm1Rwa
FVB.129-Kcnma1
MGI:99923  MP:0004433 abnormal cochlear inner hair cell physiology PMID: 17135251 
Kcnma1tm1Ruth Kcnma1tm1Ruth/Kcnma1tm1Ruth
129-Kcnma1
MGI:99923  MP:0004433 abnormal cochlear inner hair cell physiology PMID: 16763026 
Kcnma1tm1Ruth Kcnma1tm1Ruth/Kcnma1tm1Ruth
129-Kcnma1
MGI:99923  MP:0006324 abnormal cochlear nerve fiber response PMID: 16763026 
Kcnma1tm1Ruth Kcnma1tm1Ruth/Kcnma1tm1Ruth
involves: 129/Sv * C57BL/6
MGI:99923  MP:0001663 abnormal digestive system physiology PMID: 16571783 
Kcnma1tm1Ruth Kcnma1tm1Ruth/Kcnma1tm1Ruth
129-Kcnma1
MGI:99923  MP:0004736 abnormal distortion product otoacoustic emission PMID: 16763026 
Kcnma1tm1Ruth Kcnma1tm1Ruth/Kcnma1tm1Ruth
involves: 129/Sv * C57BL/6
MGI:99923  MP:0002807 abnormal eye blink conditioning behavior PMID: 15194823 
Kcnma1tm1Ruth Kcnma1tm1Ruth/Kcnma1tm1Ruth
involves: 129/Sv * C57BL/6
MGI:99923  MP:0003868 abnormal feces composition PMID: 16571783 
Kcnma1tm1Ruth Kcnma1tm1Ruth/Kcnma1tm1Ruth
involves: 129/Sv * C57BL/6
MGI:99923  MP:0001406 abnormal gait PMID: 15194823 
Kcnma1tm1Rwa Kcnma1tm1Rwa/Kcnma1tm1Rwa
FVB.129-Kcnma1
MGI:99923  MP:0001406 abnormal gait PMID: 15184377 
Kcnma1tm1Ruth Kcnma1tm1Ruth/Kcnma1tm1Ruth
129-Kcnma1
MGI:99923  MP:0006335 abnormal hearing electrophysiology PMID: 16763026 
Kcnma1tm1Ruth Kcnma1tm1Ruth/Kcnma1tm1Ruth
involves: 129/Sv * C57BL/6
MGI:99923  MP:0002066 abnormal motor capabilities/coordination/movement PMID: 15194823 
Kcnma1tm1Ruth Kcnma1tm1Ruth/Kcnma1tm1Ruth
involves: 129/Sv * C57BL/6
MGI:99923  MP:0005620 abnormal muscle contractility PMID: 19220851 
Kcnma1tm1Ruth|Kcnma1tm2.1Ruth|Tg(Myh11-cre/ERT2)1Soff Kcnma1tm1Ruth/Kcnma1tm2.1Ruth,Tg(Myh11-cre/ERT2)1Soff/0
involves: 129/Sv * C57BL/6 * FVB/N
MGI:3819268  MGI:99923  MP:0005620 abnormal muscle contractility PMID: 19220851 
Kcnma1tm1Ruth Kcnma1tm1Ruth/Kcnma1tm1Ruth
involves: 129/Sv * C57BL/6
MGI:99923  MP:0001731 abnormal postnatal growth PMID: 15194823 
Kcnma1tm1Ruth Kcnma1tm1Ruth/Kcnma1tm1Ruth
involves: 129/Sv * C57BL/6
MGI:99923  MP:0010386 abnormal urinary bladder physiology PMID: 19220851 
Kcnma1tm1Rwa Kcnma1tm1Rwa/Kcnma1tm1Rwa
FVB.129-Kcnma1
MGI:99923  MP:0010386 abnormal urinary bladder physiology PMID: 15184377 
Kcnma1tm1Ruth|Kcnma1tm2.1Ruth|Tg(Myh11-cre/ERT2)1Soff Kcnma1tm1Ruth/Kcnma1tm2.1Ruth,Tg(Myh11-cre/ERT2)1Soff/0
involves: 129/Sv * C57BL/6 * FVB/N
MGI:3819268  MGI:99923  MP:0010386 abnormal urinary bladder physiology PMID: 19220851 
Kcnma1tm1Ruth Kcnma1tm1Ruth/Kcnma1tm1Ruth
involves: 129/Sv * C57BL/6
MGI:99923  MP:0001761 abnormal urination pattern PMID: 19220851 
Kcnma1tm1Rwa Kcnma1tm1Rwa/Kcnma1tm1Rwa
FVB.129-Kcnma1
MGI:99923  MP:0001761 abnormal urination pattern PMID: 15184377 
Kcnma1tm1Ruth|Kcnma1tm2.1Ruth|Tg(Myh11-cre/ERT2)1Soff Kcnma1tm1Ruth/Kcnma1tm2.1Ruth,Tg(Myh11-cre/ERT2)1Soff/0
involves: 129/Sv * C57BL/6 * FVB/N
MGI:3819268  MGI:99923  MP:0001761 abnormal urination pattern PMID: 19220851 
Kcnma1tm1Ruth Kcnma1tm1Ruth/Kcnma1tm1Ruth
involves: 129X1/SvJ
MGI:99923  MP:0004737 absent distortion product otoacoustic emissions PMID: 15328414 
Kcnma1tm1Ruth Kcnma1tm1Ruth/Kcnma1tm1Ruth
involves: 129/Sv * C57BL/6
MGI:99923  MP:0001393 ataxia PMID: 15194823 
Kcnma1tm1Rwa Kcnma1tm1Rwa/Kcnma1tm1Rwa
FVB.129-Kcnma1
MGI:99923  MP:0001393 ataxia PMID: 15184377 
Kcnma1tm1Ruth Kcnma1tm1Ruth/Kcnma1tm1Ruth
involves: 129X1/SvJ
MGI:99923  MP:0004404 cochlear outer hair cell degeneration PMID: 15328414  17074442 
Kcnma1tm1Rwa Kcnma1tm1Rwa/Kcnma1tm1Rwa
FVB.129-Kcnma1
MGI:99923  MP:0001262 decreased body weight PMID: 15184377 
Kcnma1tm1Rwa Kcnma1tm1Rwa/Kcnma1tm1Rwa
FVB.129-Kcnma1
MGI:99923  MP:0001935 decreased litter size PMID: 15184377 
Kcnma1tm1Ruth Kcnma1tm1Ruth/Kcnma1tm1Ruth
involves: 129X1/SvJ
MGI:99923  MP:0004628 Deiters cell degeneration PMID: 15328414 
Kcnma1tm1Ruth Kcnma1tm1Ruth/Kcnma1tm1Ruth
involves: 129/Sv * C57BL/6
MGI:99923  MP:0002578 impaired ability to fire action potentials PMID: 15194823 
Kcnma1tm1Ruth Kcnma1tm1Ruth/Kcnma1tm1Ruth
involves: 129/Sv * C57BL/6
MGI:99923  MP:0001405 impaired coordination PMID: 15194823 
Kcnma1tm1Rwa Kcnma1tm1Rwa/Kcnma1tm1Rwa
FVB.129-Kcnma1
MGI:99923  MP:0001405 impaired coordination PMID: 15184377 
Kcnma1tm1Ruth Kcnma1tm1Ruth/Kcnma1tm1Ruth
involves: 129/Sv * C57BL/6
MGI:99923  MP:0001522 impaired swimming PMID: 15194823 
Kcnma1tm1Ruth Kcnma1tm1Ruth/Kcnma1tm1Ruth
involves: 129X1/SvJ
MGI:99923  MP:0006042 increased apoptosis PMID: 15328414 
Kcnma1tm1Ruth Kcnma1tm1Ruth/Kcnma1tm1Ruth
involves: 129/Sv * C57BL/6
MGI:99923  MP:0001994 increased blinking frequency PMID: 15194823 
Kcnma1tm1Ruth Kcnma1tm1Ruth/Kcnma1tm1Ruth
involves: 129/Sv * C57BL/6
MGI:99923  MP:0004037 increased muscle relaxation PMID: 19220851 
Kcnma1tm1Rwa Kcnma1tm1Rwa/Kcnma1tm1Rwa
FVB.129-Kcnma1
MGI:99923  MP:0004925 increased resistance to noise-induced hearing loss PMID: 17135251 
Kcnma1tm1Ruth Kcnma1tm1Ruth/Kcnma1tm1Ruth
involves: 129X1/SvJ
MGI:99923  MP:0004597 increased susceptibility to noise-induced hearing loss PMID: 17074442 
Kcnma1tm1Ruth Kcnma1tm1Ruth/Kcnma1tm1Ruth
involves: 129/Sv * C57BL/6
MGI:99923  MP:0002916 increased synaptic depression PMID: 15194823 
Kcnma1tm1Ruth Kcnma1tm1Ruth/Kcnma1tm1Ruth
involves: 129/Sv * C57BL/6
MGI:99923  MP:0002842 increased systemic arterial blood pressure PMID: 15194823 
Kcnma1tm1Rwa Kcnma1tm1Rwa/Kcnma1tm1Rwa
FVB.129-Kcnma1
MGI:99923  MP:0002083 premature death PMID: 15184377 
Kcnma1tm1Ruth Kcnma1tm1Ruth/Kcnma1tm1Ruth
involves: 129X1/SvJ
MGI:99923  MP:0004740 sensorineural hearing loss PMID: 15328414 
Kcnma1tm1Ruth Kcnma1tm1Ruth/Kcnma1tm1Ruth
involves: 129/Sv * C57BL/6
MGI:99923  MP:0001407 short stride length PMID: 15194823 
Kcnma1tm1Rwa Kcnma1tm1Rwa/Kcnma1tm1Rwa
FVB.129-Kcnma1
MGI:99923  MP:0001407 short stride length PMID: 15184377 
Kcnma1tm1Ruth Kcnma1tm1Ruth/Kcnma1tm1Ruth
involves: 129/Sv * C57BL/6
MGI:99923  MP:0000745 tremors PMID: 15194823 
Kcnma1tm1Rwa Kcnma1tm1Rwa/Kcnma1tm1Rwa
FVB.129-Kcnma1
MGI:99923  MP:0001396 unidirectional circling PMID: 15184377 
Kcnma1tm1Rwa Kcnma1tm1Rwa/Kcnma1tm1Rwa
FVB.129-Kcnma1
MGI:99923  MP:0003280 urinary incontinence PMID: 15184377 
Clinically-Relevant Mutations and Pathophysiology
Disease:  Generalized epilepsy and paroxysmal dyskinesia
OMIM: 609446
Orphanet: ORPHA79137
General Comments
Channel openers may have applications in stroke, epilepsy, bladder over-reactivity, asthma, hypertension, gastric hypermotility and psychoses [3,5,8].

Crystal Structures have been solved for the Intracellular Gating Rings [19,23-24].

References

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1. Brenner R, Jegla TJ, Wickenden A, Liu Y, Aldrich RW. (2000) Cloning and functional characterization of novel large conductance calcium-activated potassium channel beta subunits, hKCNMB3 and hKCNMB4. J. Biol. Chem.275 (9): 6453-61. [PMID:10692449]

2. Butler A, Tsunoda S, McCobb DP, Wei A, Salkoff L. (1993) mSlo, a complex mouse gene encoding "maxi" calcium-activated potassium channels. Science261 (5118): 221-4. [PMID:7687074]

3. Coghlan MJ, Carroll WA, Gopalakrishnan M. (2001) Recent developments in the biology and medicinal chemistry of potassium channel modulators: update from a decade of progress. J. Med. Chem.44 (11): 1627-53. [PMID:11356099]

4. Garcia-Valdes J, Zamudio FZ, Toro L, Possani LD, Possan LD. (2001) Slotoxin, alphaKTx1.11, a new scorpion peptide blocker of MaxiK channels that differentiates between alpha and alpha+beta (beta1 or beta4) complexes. FEBS Lett.505 (3): 369-73. [PMID:11576530]

5. Gribkoff VK, Starrett JE, Dworetzky SI, Hewawasam P, Boissard CG, Cook DA, Frantz SW, Heman K, Hibbard JR, Huston K, Johnson G, Krishnan BS, Kinney GG, Lombardo LA, Meanwell NA, Molinoff PB, Myers RA, Moon SL, Ortiz A, Pajor L, Pieschl RL, Post-Munson DJ, Signor LJ, Srinivas N, Taber MT, Thalody G, Trojnacki JT, Wiener H, Yeleswaram K, Yeola SW. (2001) Targeting acute ischemic stroke with a calcium-sensitive opener of maxi-K potassium channels. Nat. Med.7 (4): 471-7. [PMID:11283675]

6. Jiang Z, Wallner M, Meera P, Toro L. (1999) Human and rodent MaxiK channel beta-subunit genes: cloning and characterization. Genomics55 (1): 57-67. [PMID:9888999]

7. 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]

8. Kaczorowski GJ, Knaus HG, Leonard RJ, McManus OB, Garcia ML. (1996) High-conductance calcium-activated potassium channels; structure, pharmacology, and function. J. Bioenerg. Biomembr.28 (3): 255-67. [PMID:8807400]

9. Liu G, Shi J, Yang L, Cao L, Park SM, Cui J, Marx SO. (2004) Assembly of a Ca2+-dependent BK channel signaling complex by binding to beta2 adrenergic receptor. EMBO J.23 (11): 2196-205. [PMID:15141163]

10. Meera P, Wallner M, Song M, Toro L. (1997) Large conductance voltage- and calcium-dependent K+ channel, a distinct member of voltage-dependent ion channels with seven N-terminal transmembrane segments (S0-S6), an extracellular N terminus, and an intracellular (S9-S10) C terminus. Proc. Natl. Acad. Sci. U.S.A.94 (25): 14066-71. [PMID:9391153]

11. Persohn E, Malherbe P, Richards JG. (1992) Comparative molecular neuroanatomy of cloned GABAA receptor subunits in the rat CNS. J. Comp. Neurol.326 (2): 193-216. [PMID:1336019]

12. Sanchez M, McManus OB. (1996) Paxilline inhibition of the alpha-subunit of the high-conductance calcium-activated potassium channel. Neuropharmacology35 (7): 963-8. [PMID:8938726]

13. Strøbaek D, Christophersen P, Holm NR, Moldt P, Ahring PK, Johansen TE, Olesen SP. (1996) Modulation of the Ca(2+)-dependent K+ channel, hslo, by the substituted diphenylurea NS 1608, paxilline and internal Ca2+. Neuropharmacology35 (7): 903-14. [PMID:8938721]

14. Tseng-Crank J, Foster CD, Krause JD, Mertz R, Godinot N, DiChiara TJ, Reinhart PH. (1994) Cloning, expression, and distribution of functionally distinct Ca(2+)-activated K+ channel isoforms from human brain. Neuron13 (6): 1315-30. [PMID:7993625]

15. Valverde MA, Rojas P, Amigo J, Cosmelli D, Orio P, Bahamonde MI, Mann GE, Vergara C, Latorre R. (1999) Acute activation of Maxi-K channels (hSlo) by estradiol binding to the beta subunit. Science285 (5435): 1929-31. [PMID:10489376]

16. Wei A, Solaro C, Lingle C, Salkoff L. (1994) Calcium sensitivity of BK-type KCa channels determined by a separable domain. Neuron13 (3): 671-81. [PMID:7917297]

17. Weiger TM, Holmqvist MH, Levitan IB, Clark FT, Sprague S, Huang WJ, Ge P, Wang C, Lawson D, Jurman ME, Glucksmann MA, Silos-Santiago I, DiStefano PS, Curtis R. (2000) A novel nervous system beta subunit that downregulates human large conductance calcium-dependent potassium channels. J. Neurosci.20 (10): 3563-70. [PMID:10804197]

18. Wisden W, Laurie DJ, Monyer H, Seeburg PH. (1992) The distribution of 13 GABAA receptor subunit mRNAs in the rat brain. I. Telencephalon, diencephalon, mesencephalon. J. Neurosci.12 (3): 1040-62. [PMID:1312131]

19. Wu Y, Yang Y, Ye S, Jiang Y. (2010) Structure of the gating ring from the human large-conductance Ca(2+)-gated K(+) channel. Nature466 (7304): 393-7. [PMID:20574420]

20. Yan J, Aldrich RW. (2010) LRRC26 auxiliary protein allows BK channel activation at resting voltage without calcium. Nature466 (7305): 513-6. [PMID:20613726]

21. Yan J, Aldrich RW. (2012) BK potassium channel modulation by leucine-rich repeat-containing proteins. Proc. Natl. Acad. Sci. U.S.A.109 (20): 7917-22. [PMID:22547800]

22. Yao J, Chen X, Li H, Zhou Y, Yao L, Wu G, Chen X, Zhang N, Zhou Z, Xu T, Wu H, Ding J. (2005) BmP09, a "long chain" scorpion peptide blocker of BK channels. J. Biol. Chem.280 (15): 14819-28. [PMID:15695820]

23. Yuan P, Leonetti MD, Hsiung Y, MacKinnon R. (2012) Open structure of the Ca2+ gating ring in the high-conductance Ca2+-activated K+ channel. Nature481 (7379): 94-7. [PMID:22139424]

24. Yuan P, Leonetti MD, Pico AR, Hsiung Y, MacKinnon R. (2010) Structure of the human BK channel Ca2+-activation apparatus at 3.0 A resolution. Science329 (5988): 182-6. [PMID:20508092]

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-activated potassium channels: KCa1.1. Last modified on 17/01/2017. Accessed on 25/02/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=380.