SK3
Description: potassium intermediate/small conductance calcium-activated channel, subfamily N, member 3 Gene: Kcnn3 Alias: SK3, hSK3, SKCA3, KCa2.3, KCNN3
Small conductance Ca2+ -activated K+ channels (SK chan- nels) are important regulators of excitability, endogenous firing pattern and synaptic integration in many neurons (Bond et al., 2005 [1104]).
Pyramidal neurons of the cortex and hippocampus display a calcium-activated slow afterhyperpolarization (sAHP) that plays a key role in regulating cell firing (Schwindt et al., 1988a [1094],b [1095]; Stocker et al., 1999 [550]) and is the target for regulation by multiple neurotransmitters (Nicoll, 1988 [1096]). Biophysical and electrophysiological studies have suggested that this sAHP is mediated by a calcium-activated potassium current. However, despite extensive studies, the identity of the ion channels underlying the sAHP remains uncertain (Sah and Faber, 2002 [1097]; Vogalis et al., 2003 [13). In the mid-1990s, with the discovery of the SKCa family of potassium channels (KCa2.x) (Kohler et al., 1996 [1099]; Gutman et al., 2003 [760]), the search for the ion channels responsible for the sAHP appeared to have reached fruition (Vergara et al., 1998 [1100]; Bond et al., 1999 [1101]). But the slow AHP current in a transgeneic mouse, expressing a truncated SKCa subunit (SK3-1B) capable of acting as a dominant negative for the entire family of SKCa–IKCa channels contradicted those findings: Expression of SK3-1B profoundly inhibited medium AHP current but again had no discernable effect on IsAHP. These results are inconsistent with the proposal that SKCa channels mediate IsAHP in pyramidal cells and indicate that a different potassium channel mediates this current. (Villalobos [142])
Gene
Transcript
Species | NCBI accession | Length (nt) | |
---|---|---|---|
Human | NM_002249.6 | 13034 | |
Mouse | NM_080466.2 | 7617 | |
Rat | NM_019315.3 | 2518 |
Protein Isoforms
Isoforms
Post-Translational Modifications
SK channels and the peripherally expressed intermediate conductance Ca2+ -activated K+ channel (IK; Ishii et al., 1997), constitute a molecular family of voltage-independent channels, that are gated by Ca2+ binding to calmodulin (CAM) tightly associated with a CAM- binding domain (CAMBD) in the C-terminal region (Xia et al., 1998 [542]; Khanna et al., 1999 [1105]). Crystallographic data from C-terminal peptides of the SK2 channel indicate that dimers of CAMBD associate with two CAM molecules, each binding 1 or 2 Ca2+ at the EF hand motifs 1 and 2 (Schumacher et al., 2001 [543]).
SK3 predicted AlphaFold size
Methodology for AlphaFold size prediction and disclaimer are available here
Central nervous system
SK3 is primarily expressed in subcortical regions , substantia nigra, amygdala, caudate nucleus, thalamus, hippocampus, ventral tegmental area, cerebellum, corpus callosum and spinal cord [1459], [539].
For further information about the expression of SK in CNS and their function see Pedarzani and Stocker 2008. [1481]
Perpheral tissue [1482], [539]
SK3 shows distinctive distribution to the small intestine, rectum, omentum, myometrium, skeletal muscles, lymphocytes, prostate, heart, kidney, pituitary gland, liver, pancreas and colon.
Rat, mouse and cat spinal cord show a differential and overlapping expression of SK2 and SK3 isoforms across specific types of α-motoneurons. In rodents, SK2 is expressed in all α-motoneurons whereas SK3 is expressed preferentially in small-diameter ones; in cats, SK3 is expressed in all α-motoneurons. [1483]
SK3 channel expression is punctate in nature and largely confined to varicose fibers, which likely represent subcellular compartments of high synaptic. Only occasionally, somatic immunostaining was observed like in the locus coeruleus or in tegmental nuclei. [1479]
SK3 channels in muscle cells are crucial for pregnancy progresses such as myometrial tranquility. SK3 channels are the first channels for which overexpression led to a delay or cessation of parturition (Pierce [154], Bond [1101]).
Native SK channels have a characteristic pharmacology. They can be blocked by the bee venom toxin apamin and several selective small molecule blockers that we have developed (such as UCL 1848) that are active at nanomolar or subnanomolar concentrations (Chen [1102], Faber [1103]).
SK3 forms functional heteromeric channels with SK1 and SK2. (Monaghan [2])
CyPPA was found to be a positive modulator of hSK3. (Hougaard [155])
References
Villalobos C
et al.
SKCa channels mediate the medium but not the slow calcium-activated afterhyperpolarization in cortical neurons.
J. Neurosci.,
2004
Apr
7
, 24 (3537-42).
Monaghan AS
et al.
The SK3 subunit of small conductance Ca2+-activated K+ channels interacts with both SK1 and SK2 subunits in a heterologous expression system.
J. Biol. Chem.,
2004
Jan
9
, 279 (1003-9).
Pierce SL
et al.
Overexpression of SK3 channels dampens uterine contractility to prevent preterm labor in mice.
Biol. Reprod.,
2008
Jun
, 78 (1058-63).
Hougaard C
et al.
Selective positive modulation of the SK3 and SK2 subtypes of small conductance Ca2+-activated K+ channels.
Br. J. Pharmacol.,
2007
Jul
, 151 (655-65).
Hosseini R
et al.
SK3 is an important component of K(+) channels mediating the afterhyperpolarization in cultured rat SCG neurones.
J. Physiol. (Lond.),
2001
Sep
1
, 535 (323-34).
Barfod ET
et al.
Cloning and functional expression of a liver isoform of the small conductance Ca2+-activated K+ channel SK3.
Am. J. Physiol., Cell Physiol.,
2001
Apr
, 280 (C836-42).
Bond CT
et al.
Respiration and parturition affected by conditional overexpression of the Ca2+-activated K+ channel subunit, SK3.
Science,
2000
Sep
15
, 289 (1942-6).
Xia XM
et al.
Mechanism of calcium gating in small-conductance calcium-activated potassium channels.
Nature,
1998
Oct
1
, 395 (503-7).
Schumacher MA
et al.
Structure of the gating domain of a Ca2+-activated K+ channel complexed with Ca2+/calmodulin.
Nature,
2001
Apr
26
, 410 (1120-4).
Stocker M
et al.
An apamin-sensitive Ca2+-activated K+ current in hippocampal pyramidal neurons.
Proc. Natl. Acad. Sci. U.S.A.,
1999
Apr
13
, 96 (4662-7).
Gutman GA
et al.
International Union of Pharmacology. XLI. Compendium of voltage-gated ion channels: potassium channels.
Pharmacol. Rev.,
2003
Dec
, 55 (583-6).
Schwindt PC
et al.
Influence of anomalous rectifier activation on afterhyperpolarizations of neurons from cat sensorimotor cortex in vitro.
J. Neurophysiol.,
1988
Feb
, 59 (468-81).
Schwindt PC
et al.
Slow conductances in neurons from cat sensorimotor cortex in vitro and their role in slow excitability changes.
J. Neurophysiol.,
1988
Feb
, 59 (450-67).
Nicoll RA
The coupling of neurotransmitter receptors to ion channels in the brain.
Science,
1988
Jul
29
, 241 (545-51).
Sah P
et al.
Channels underlying neuronal calcium-activated potassium currents.
Prog. Neurobiol.,
2002
Apr
, 66 (345-53).
Vogalis F
et al.
SK channels and the varieties of slow after-hyperpolarizations in neurons.
Eur. J. Neurosci.,
2003
Dec
, 18 (3155-66).
Köhler M
et al.
Small-conductance, calcium-activated potassium channels from mammalian brain.
Science,
1996
Sep
20
, 273 (1709-14).
Vergara C
et al.
Calcium-activated potassium channels.
Curr. Opin. Neurobiol.,
1998
Jun
, 8 (321-9).
Bond CT
et al.
Small-conductance calcium-activated potassium channels.
Ann. N. Y. Acad. Sci.,
1999
Apr
30
, 868 (370-8).
Chen JQ
et al.
bis-Quinolinium cyclophanes: 8,14-diaza-1,7(1, 4)-diquinolinacyclotetradecaphane (UCL 1848), a highly potent and selective, nonpeptidic blocker of the apamin-sensitive Ca(2+)-activated K(+) channel.
J. Med. Chem.,
2000
Sep
21
, 43 (3478-81).
Faber ES
et al.
Physiological role of calcium-activated potassium currents in the rat lateral amygdala.
J. Neurosci.,
2002
Mar
1
, 22 (1618-28).
Bond CT
et al.
SK channels in excitability, pacemaking and synaptic integration.
Curr. Opin. Neurobiol.,
2005
Jun
, 15 (305-11).
Khanna R
et al.
hSK4/hIK1, a calmodulin-binding KCa channel in human T lymphocytes. Roles in proliferation and volume regulation.
J. Biol. Chem.,
1999
May
21
, 274 (14838-49).
Wulff H
et al.
K+ channel modulators for the treatment of neurological disorders and autoimmune diseases.
Chem. Rev.,
2008
May
, 108 (1744-73).
Sailer CA
et al.
Comparative immunohistochemical distribution of three small-conductance Ca2+-activated potassium channel subunits, SK1, SK2, and SK3 in mouse brain.
Mol. Cell. Neurosci.,
2004
Jul
, 26 (458-69).
Pedarzani P
et al.
Molecular and cellular basis of small--and intermediate-conductance, calcium-activated potassium channel function in the brain.
Cell. Mol. Life Sci.,
2008
Oct
, 65 (3196-217).
Chen MX
et al.
Small and intermediate conductance Ca(2+)-activated K+ channels confer distinctive patterns of distribution in human tissues and differential cellular localisation in the colon and corpus cavernosum.
Naunyn Schmiedebergs Arch. Pharmacol.,
2004
Jun
, 369 (602-15).
Deardorff AS
et al.
Expression of postsynaptic Ca2+-activated K+ (SK) channels at C-bouton synapses in mammalian lumbar -motoneurons.
J. Physiol. (Lond.),
2013
Feb
15
, 591 (875-97).
Credits
To cite this page: [Contributors] Channelpedia https://channelpedia.epfl.ch/wikipages/67/ , accessed on 2024 Dec 02