SK channel


SK channel

SK channels (Small conductance calcium-activated K (potassium) channels) are a subfamily of Ca2+-activated K+ channels.cite journal | author = Bond CT, Maylie J, Adelman JP | title = Small-conductance calcium-activated potassium channels | journal = Ann. N. Y. Acad. Sci. | volume = 868 | issue = | pages = 370–8 | year = 1999 | pmid = 10414306 | doi = | issn = | url = http://www.annalsnyas.org/cgi/content/abstract/868/1/370 ] SK channels are a type of ion channel allowing potassium cations to cross the cell membrane and are activated (opened) by an increase in the concentration of intracellular calcium. Their activation limits the firing frequency of action potentials and are important for regulating afterhyperpolarization in central neurons and other types of electrically excitable cells.cite journal | author = Faber ES, Sah P | title = Functions of SK channels in central neurons | journal = Clin. Exp. Pharmacol. Physiol. | volume = 34 | issue = 10 | pages = 1077–83 | year = 2007 | pmid = 17714097 | doi = 10.1111/j.1440-1681.2007.04725.x | issn = ] SK channels are thought to be involved in synaptic plasticity and therefore play important roles in memory and learning.cite journal | author = Stackman RW, Hammond RS, Linardatos E, Gerlach A, Maylie J, Adelman JP, Tzounopoulos T | title = Small conductance Ca2+-activated K+ channels modulate synaptic plasticity and memory encoding | journal = J. Neurosci. | volume = 22 | issue = 23 | pages = 10163–71 | year = 2002 | pmid = 12451117 | doi = | issn = | url = http://www.jneurosci.org/cgi/content/abstract/22/23/10163 ]

tructure

SK potassium channels share the same basic architecture with shaker-like voltage-gated potassium channels.cite journal | author = Maylie J, Bond CT, Herson PS, Lee WS, Adelman JP | title = Small conductance Ca2+-activated K+ channels and calmodulin | journal = J. Physiol. (Lond.) | volume = 554 | issue = Pt 2 | pages = 255–61 | year = 2004 | pmid = 14500775 | doi = 10.1113/jphysiol.2003.049072 | issn = ] Four identical subunits associate to form a symmetric tetramer. Each of the subunits has six hydrophobic alpha helical domains which insert into the cell membrane. A loop between the fifth and sixth trans membrane domain forms the potassium ion selectivity filter.

In addition, SK potassium channels are tightly associated with the protein calmodulin which accounts for the calcium sensitivity of these channels.cite journal | author = Schumacher MA, Rivard AF, Bächinger HP, Adelman JP | title = Structure of the gating domain of a Ca2+-activated K+ channel complexed with Ca2+/calmodulin | journal = Nature | volume = 410 | issue = 6832 | pages = 1120–4 | year = 2001 | pmid = 11323678 | doi = 10.1038/35074145 | issn = ]

Classification

The SK channel family contains 4 members - SK1, SK2, SK3, and SK4.

Blockers

All SK channels can be pharmacologically blocked by quartenary ammonium salts of a plant-derived neurotoxin bicuculline.cite journal | author = Khawaled R, Bruening-Wright A, Adelman JP, Maylie J | title = Bicuculline block of small-conductance calcium-activated potassium channels | journal = Pflugers Arch. | volume = 438 | issue = 3 | pages = 314–21 | year = 1999 | pmid = 10398861 | doi = 10.1007/s004240050915 | issn = ] In addition, SK channels(SK1-SK3) are sensitive to blockade by the bee venom [apamin] , cite journal | author = Blatz AL, Magleby KL | title = Single apamin-blocked Ca-activated K+ channels of small conductance in cultured rat skeletal muscle | journal = Nature | volume = 323 | issue = 6090 | pages = 718–20 | year = 1986 | pmid = 2430185 | doi = 10.1038/323718a0 | issn = ] but SK4 (IK) is not. and the scorpion venom tamapin.cite journal | author = Pedarzani P, D'hoedt D, Doorty KB, Wadsworth JD, Joseph JS, Jeyaseelan K, Kini RM, Gadre SV, Sapatnekar SM, Stocker M, Strong PN | title = Tamapin, a venom peptide from the Indian red scorpion (Mesobuthus tamulus) that targets small conductance Ca2+-activated K+ channels and afterhyperpolarization currents in central neurons | journal = J. Biol. Chem. | volume = 277 | issue = 48 | pages = 46101–9 | year = 2002 | pmid = 12239213 | doi = 10.1074/jbc.M206465200 | issn = ]

Modulators

Allosteric modulators of SK channels work by changing the apparent calcium sensitivity of the channels. Examples include:
* Non selective positive modulators of SK channels: EBIO (1-Ethyl-2-BenzimIdazolinOne),cite journal | author = Pedarzani P, Mosbacher J, Rivard A, Cingolani LA, Oliver D, Stocker M, Adelman JP, Fakler B | title = Control of electrical activity in central neurons by modulating the gating of small conductance Ca2+-activated K+ channels | journal = J. Biol. Chem. | volume = 276 | issue = 13 | pages = 9762–9 | year = 2001 | pmid = 11134030 | doi = 10.1074/jbc.M010001200 | issn = ] NS309 (6,7-dichloro-1H-indole-2,3-dione 3-oxime)cite journal | author = Strøbaek D, Teuber L, Jørgensen TD, Ahring PK, Kjaer K, Hansen RS, Olesen SP, Christophersen P, Skaaning-Jensen B | title = Activation of human IK and SK Ca2+-activated K+ channels by NS309 (6,7-dichloro-1H-indole-2,3-dione 3-oxime) | journal = Biochim. Biophys. Acta | volume = 1665 | issue = 1-2 | pages = 1–5 | year = 2004 | pmid = 15471565 | doi = 10.1016/j.bbamem.2004.07.006 | issn = ]
* SK-3 selective positive modulators : CyPPA (NS6277; Cyclohexyl-(2-(3,5-dimethyl-Pyrazol-1-yl)-6-methyl-Pyrimidin-4-yl)-Amine)cite journal | author = Hougaard C, Eriksen BL, Jørgensen S, Johansen TH, Dyhring T, Madsen LS, Strøbaek D, Christophersen P | title = Selective positive modulation of the SK3 and SK2 subtypes of small conductance Ca2+-activated K+ channels | journal = Br. J. Pharmacol. | volume = 151 | issue = 5 | pages = 655–65 | year = 2007 | pmid = 17486140 | doi = 10.1038/sj.bjp.0707281 | issn = ]

References

External links

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