Calcium-activated potassium channel

Calcium-activated potassium channels are potassium channels gated by calcium, or are structurally or phylogenetically related to calcium gated channels. In humans they are divided into BK channels, IK channels, and SK channels based on their conductance (big, intermediate, and small conductance).

This family of ion channels is, for the most part, activated by intracellular Ca2+ and contains 8 members in the human genome. However, some of these channels (the KCa4 and KCa5 channels) are responsive instead other intracellular ligands, such as Na+, Cl−, and pH. Furthermore, multiple members of family are both ligand and voltage activated, further complicating the description of this family. The KCa channel α subunits have six or seven transmembrane segments, similar to the KV channels but occasionally with an an additional N-terminal transmembrane helix. The α subunits make homo- and hetero-tetrameric complexes. The calcium binding domain may be contained in the α subunit sequence, as in KCa1, or may be through an additional calcium binding protein such as calmodulin.

Homology classification

Human KCa Channels

Below is a list of the 8 known human calcium-activated potassium channel grouped according to sequence homology of transmembrane hydrophobic cores:[1]

BK channel

SK channel

IK channel

Other subfamilies

Prokaryotic KCa Channels

A number of prokaryotic KCa channels have been described, both structurally and functionally. All are either gated by calcium or other ligands and are homologus to the human KCa channels, in particular the KCa1.1 gating ring. These structures have served as templates for ligand gating.

ProteinSpeciesLigandFunctionReference
KchEscherichia coliUnknownChannel[2][3]
MthKMethanothermobacter thermautotrophicusCalcium, Cadmium, Barium, pHChannel[4][5][6][7][8]
TrkA/TrkHVibrio parahaemolyticusATP, ADPChannel[9][10]
KtrABBacillus subtilisATP, ADPTransporter[11]
GsuKGeobacter sulfurreducensCalcium, ADP, NADChannel[12]
TM1088Thermotoga maritimaUnknownUnknown[13]

See also

References

  1. ↑ Wei AD, Gutman GA, Aldrich R, Chandy KG, Grissmer S, Wulff H (Dec 2005). "International Union of Pharmacology. LII. Nomenclature and molecular relationships of calcium-activated potassium channels". Pharmacological Reviews 57 (4): 463–72. doi:10.1124/pr.57.4.9. PMID 16382103.
  2. ↑ Milkman R (Apr 1994). "An Escherichia coli homologue of eukaryotic potassium channel proteins". Proceedings of the National Academy of Sciences of the United States of America 91 (9): 3510–4. PMID 8170937.
  3. ↑ Jiang Y, Pico A, Cadene M, Chait BT, MacKinnon R (Mar 2001). "Structure of the RCK domain from the E. coli K+ channel and demonstration of its presence in the human BK channel". Neuron 29 (3): 593–601. PMID 11301020.
  4. ↑ Jiang Y, Lee A, Chen J, Cadene M, Chait BT, MacKinnon R (May 2002). "Crystal structure and mechanism of a calcium-gated potassium channel". Nature 417 (6888): 515–22. Bibcode:2002Natur.417..515J. doi:10.1038/417515a. PMID 12037559.
  5. ↑ Smith FJ, Pau VP, Cingolani G, Rothberg BS (2013). "Structural basis of allosteric interactions among Ca2+-binding sites in a K+ channel RCK domain". Nature Communications 4: 2621. Bibcode:2013NatCo...4E2621S. doi:10.1038/ncomms3621. PMID 24126388.
  6. ↑ Ye S, Li Y, Chen L, Jiang Y (Sep 2006). "Crystal structures of a ligand-free MthK gating ring: insights into the ligand gating mechanism of K+ channels". Cell 126 (6): 1161–73. doi:10.1016/j.cell.2006.08.029. PMID 16990139.
  7. ↑ Dvir H, Valera E, Choe S (Aug 2010). "Structure of the MthK RCK in complex with cadmium". Journal of Structural Biology 171 (2): 231–7. doi:10.1016/j.jsb.2010.03.020. PMID 20371380.
  8. ↑ Smith FJ, Pau VP, Cingolani G, Rothberg BS (Dec 2012). "Crystal structure of a Ba(2+)-bound gating ring reveals elementary steps in RCK domain activation". Structure 20 (12): 2038–47. doi:10.1016/j.str.2012.09.014. PMID 23085076.
  9. ↑ Cao Y, Jin X, Huang H, Derebe MG, Levin EJ, Kabaleeswaran V et al. (Mar 2011). "Crystal structure of a potassium ion transporter, TrkH". Nature 471 (7338): 336–40. Bibcode:2011Natur.471..336C. doi:10.1038/nature09731. PMC 3077569. PMID 21317882.
  10. ↑ Cao Y, Pan Y, Huang H, Jin X, Levin EJ, Kloss B et al. (Apr 2013). "Gating of the TrkH ion channel by its associated RCK protein TrkA". Nature 496 (7445): 317–22. Bibcode:2013Natur.496..317C. doi:10.1038/nature12056. PMC 3726529. PMID 23598339.
  11. ↑ Vieira-Pires RS, Szollosi A, Morais-Cabral JH (Apr 2013). "The structure of the KtrAB potassium transporter". Nature 496 (7445): 323–8. Bibcode:2013Natur.496..323V. doi:10.1038/nature12055. PMID 23598340.
  12. ↑ Kong C, Zeng W, Ye S, Chen L, Sauer DB, Lam Y et al. (2012). "Distinct gating mechanisms revealed by the structures of a multi-ligand gated K(+) channel". eLife 1: e00184. doi:10.7554/eLife.00184. PMC 3510474. PMID 23240087.
  13. ↑ Deller MC, Johnson HA, Miller MD, Spraggon G, Elsliger MA, Wilson IA et al. (2015). "Crystal Structure of a Two-Subunit TrkA Octameric Gating Ring Assembly". PloS One 10 (3): e0122512. doi:10.1371/journal.pone.0122512. PMC 4380455. PMID 25826626.

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