Channelpedia

SK3

Description: potassium intermediate/small conductance calcium-activated channel, subfamily N, member 3
Gene: Kcnn3     Synonyms: 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])


Experimental data


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Gene

RGD ID Chromosome Position Species
2964 2 181715888-181860459 Rat
733382 3 89324086-89476416 Mouse
733381 1 154679902-154842754 Human

Kcnn3 : potassium intermediate/small conductance calcium-activated channel, subfamily N, member 3


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Transcript

Acc No Sequence Length Source
NM_019315 n/A n/A NCBI
NM_080466 n/A n/A NCBI
NM_002249 n/A n/A NCBI
NM_170782 n/A n/A NCBI

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Ontology

Accession Name Definition Evidence
GO:0005886 plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins. IMP
GO:0016021 integral to membrane Penetrating at least one phospholipid bilayer of a membrane. May also refer to the state of being buried in the bilayer with no exposure outside the bilayer. When used to describe a protein, indicates that all or part of the peptide sequence is embedded in the membrane. IEA

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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])


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Protein


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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]).


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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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Expression

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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Functional

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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Kinetics


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Model


References

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).

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. et al. The coupling of neurotransmitter receptors to ion channels in the brain.
Science, 1988 Jul 29 , 241 (545-51).

Faber ES. 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).

Bond CT. et al. Small-conductance, calcium-activated potassium channels from mammalian brain.
Science, 1996 Sep 20 , 273 (1709-14).

Adelman JP. 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).

Adelman JP. et al. SK channels in excitability, pacemaking and synaptic integration.
Curr. Opin. Neurobiol., 2005 Jun , 15 (305-11).

1459

1483


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