Channelpedia

SK3

Description: potassium intermediate/small conductance calcium-activated channel, subfamily N, member 3
Gene: Kcnn3
Alias: SK3, hSK3, SKCA3, KCa2.3, KCNN3

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Introduction

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])


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Gene

Species NCBI gene ID Chromosome Position
Human 3782 1 172826
Mouse 140493 3 152330
Rat 54263 2 159064

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Transcript

Species NCBI accession Length (nt)
Human NM_002249.6 13034
Mouse NM_080466.2 7617
Rat NM_019315.3 2518

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Protein Isoforms

Species Uniprot ID Length (aa)
Human Q9UGI6 731
Mouse P58391 732
Rat P70605 732

Isoforms

Transcript
Length (nt)
Protein
Length (aa)
Variant
Isoform

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Post-Translational Modifications

PTM
Position
Type

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Structure

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

Species Area (Å2) Reference
Human 6956.27 source
Mouse 7677.78 source
Rat 8715.98 source

Methodology for AlphaFold size prediction and disclaimer are available here


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Expression and Distribution

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]


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CNS Sub-cellular Distribution

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]


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Function

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]).


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Interaction

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

154

157

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).

543

550

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).

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).

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).


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Credits

To cite this page: [Contributors] Channelpedia https://channelpedia.epfl.ch/wikipages/67/ , accessed on 2024 Dec 02



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