SK2
Description: potassium intermediate/small conductance calcium-activated channel, subfamily N, member 2 Gene: Kcnn2 Alias: SK2, hSK2, SKCA2, KCa2.2, Kcnn2
Ca2+-activated K+ channels are activated by rises in intracellular Ca2+. The KCa potassium channel family includes at least three subfamilies, KCa1–3 [539]. Channels containing the KCa1.1 alpha-subunit (BK channels) have large single channel conductance and are maximally activated by micromolar concentrations of intracellular free calcium and concurrent depolarization. Their kinetic and pharmacological properties are modified upon assembly with membrane standing beta-subunits [540]. The KCa2 subfamily of small conductance Ca2+-activated K+ channels, also known as SK channels, has three closely related members SK1 (KCa2.1), SK2 (KCa2.2), and SK3 (KCa2.3), which are characterized by a small single channel conductance. The IK channel (KCa3.1) shows an intermediate single channel conductance. Both SK and IK channels are voltage-independent and activated by submicromolar concentrations of intracellular free Ca2+. The gating of SK and IK channels is induced upon Ca2+ binding to calmodulin, which is constitutively bound to each channel subunit. Ca2+ binding to calmodulin induces a conformational change, which leads to the opening of these channels [541], [542], [543].
Gene
Transcript
Species | NCBI accession | Length (nt) | |
---|---|---|---|
Human | NM_021614.4 | 2760 | |
Mouse | NM_001312905.2 | 3692 | |
Rat | NM_001309404.1 | 2069 |
Protein Isoforms
Isoforms
Post-Translational Modifications
SK channels consist of heterotetrameric subunit assembly of four identical subunits that associate to form a symmetric tetramer SK channels [1110]. Each of the subunits have six transmembrane segments (S1-S6) and intracellular N- and C-termini.4 However, SK2 channels only contain two positively charged amino acids in the S4 segment and are therefore insensitive to changes in membrane voltage. [1459]
Crystallographic studies suggest that SK channels gate as a dimer-of-dimers, and that the physical gate of SK channels resides at or near the selectivity filter of the channels. In addition, Ca(2+)-independent interactions between the SK channel alpha subunits and calmoduline are necessary for proper membrane trafficking. [1112]
SK2 predicted AlphaFold size
Methodology for AlphaFold size prediction and disclaimer are available here
Central nervous system
SK channels are widely expressed in the central nervous system thereby potentially contributing to neuronal excitability control and they are critical regulators of neuronal excitability in hippocampus [1106]).
For further information about SK channels expression see table 1 Densities of immunoreactivity for SK1, SK2, and SK3 proteins in various compartments of the mouse central nervous system in Sailer et al., 2006 [1479]).
SK2 channel labeling is strongest in the CA1–CA2 stratum radiatum and stratum oriens [1479]. It is also expressed in amígdala, corpus callosum, thalamus, caudate nucleus, and substantia nigra. [539] SK1 and SK2 are often expressed in the same neurons, predominantly in the neocortex, hippocampal formation, cerebellum, and thalamus [1479]).
SK channels, predominantly of the SK2 type, have been identified in sensory systems such as the retina [545] and the cochlear inner and outer hair cells [546]. SK channels have also been described in heart [546], liver [547], skeletal muscle [548], [147], and visceral smooth muscle [549].
In most brain regions, SK2 immunostaining is restricted to the plasma membrane of neuronal somata of defined fiber tracts. However, in some brain regions like the basolateral amygdala or the medial habenula, a more diffuse staining pattern is observed and it is unable to clearly assign the origin of immunostaining to defined neuronal compartments. It is also asscociated with both neuronal somata and fibers. SK2 channels are expressed in the PSD of dendritic spines on CA1 pyramidal neurons [1479] and some results suggest that protein SK2-L may play a role in the subcellular localization of native SK2-containing channels [1480].
The SK channel-mediated current regulates membrane excitability, increases the precision of neuronal firing [550], and modulates synaptic plasticity by regulating excitatory synaptic transmission in the amygdala [551] and the hippocampus [552]. Inhibition of SK channels facilitates hippocampal independent [553] as well as dependent learning [554] and improves memory performance [553].
Apamin
The bee venom toxin apamin inhibits exclusively the three cloned SK channel subtypes (SK1, SK2, and SK3) with different affinity, highest for SK2, lowest for SK1, and intermediate for SK3 channels. [141]
Methyl-laudanosine
The alkaloid methyl-laudanosine blocks SK1, SK2 and SK3 currents with equal potency, IK currents were unaffected. [143]
References
Nolting A
et al.
An amino acid outside the pore region influences apamin sensitivity in small conductance Ca2+-activated K+ channels.
J. Biol. Chem.,
2007
Feb
9
, 282 (3478-86).
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).
Scuvée-Moreau J
et al.
Electrophysiological characterization of the SK channel blockers methyl-laudanosine and methyl-noscapine in cell lines and rat brain slices.
Br. J. Pharmacol.,
2004
Nov
, 143 (753-64).
D'Hoedt D
et al.
Domain analysis of the calcium-activated potassium channel SK1 from rat brain. Functional expression and toxin sensitivity.
J. Biol. Chem.,
2004
Mar
26
, 279 (12088-92).
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).
Benton DC
et al.
Small conductance Ca2+-activated K+ channels formed by the expression of rat SK1 and SK2 genes in HEK 293 cells.
J. Physiol. (Lond.),
2003
Nov
15
, 553 (13-9).
Ro S
et al.
Molecular properties of small-conductance Ca2+-activated K+ channels expressed in murine colonic smooth muscle.
Am. J. Physiol. Gastrointest. Liver Physiol.,
2001
Oct
, 281 (G964-73).
Kong JH
et al.
Expression of the SK2 calcium-activated potassium channel is required for cholinergic function in mouse cochlear hair cells.
J. Physiol. (Lond.),
2008
Nov
15
, 586 (5471-85).
Bruening-Wright A
et al.
Evidence for a deep pore activation gate in small conductance Ca2+-activated K+ channels.
J. Gen. Physiol.,
2007
Dec
, 130 (601-10).
Johnson SL
et al.
Genetic deletion of SK2 channels in mouse inner hair cells prevents the developmental linearization in the Ca2+ dependence of exocytosis.
J. Physiol. (Lond.),
2007
Sep
1
, 583 (631-46).
Hammond RS
et al.
Small-conductance Ca2+-activated K+ channel type 2 (SK2) modulates hippocampal learning, memory, and synaptic plasticity.
J. Neurosci.,
2006
Feb
8
, 26 (1844-53).
Nie L
et al.
Cloning and expression of a small-conductance Ca(2+)-activated K+ channel from the mouse cochlea: coexpression with alpha9/alpha10 acetylcholine receptors.
J. Neurophysiol.,
2004
Apr
, 91 (1536-44).
Wei AD
et al.
International Union of Pharmacology. LII. Nomenclature and molecular relationships of calcium-activated potassium channels.
Pharmacol. Rev.,
2005
Dec
, 57 (463-72).
Orio P
et al.
New disguises for an old channel: MaxiK channel beta-subunits.
News Physiol. Sci.,
2002
Aug
, 17 (156-61).
Fanger CM
et al.
Calmodulin mediates calcium-dependent activation of the intermediate conductance KCa channel, IKCa1.
J. Biol. Chem.,
1999
Feb
26
, 274 (5746-54).
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.
Differential distribution of three Ca(2+)-activated K(+) channel subunits, SK1, SK2, and SK3, in the adult rat central nervous system.
Mol. Cell. Neurosci.,
2000
May
, 15 (476-93).
Klöcker N
et al.
Developmental expression of the small-conductance Ca(2+)-activated potassium channel SK2 in the rat retina.
Mol. Cell. Neurosci.,
2001
Mar
, 17 (514-20).
Glowatzki E
et al.
Cholinergic synaptic inhibition of inner hair cells in the neonatal mammalian cochlea.
Science,
2000
Jun
30
, 288 (2366-8).
Schetz JA
et al.
Pharmacology of the high-affinity apamin receptor in rabbit heart.
Cardiovasc. Res.,
1995
Nov
, 30 (755-62).
Hugues M
et al.
The Ca2+-dependent slow K+ conductance in cultured rat muscle cells: characterization with apamin.
EMBO J.,
1982
, 1 (1039-42).
Banks BE
et al.
Apamin blocks certain neurotransmitter-induced increases in potassium permeability.
Nature,
1979
Nov
22
, 282 (415-7).
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).
Faber ES
et al.
SK channels regulate excitatory synaptic transmission and plasticity in the lateral amygdala.
Nat. Neurosci.,
2005
May
, 8 (635-41).
Ngo-Anh TJ
et al.
SK channels and NMDA receptors form a Ca2+-mediated feedback loop in dendritic spines.
Nat. Neurosci.,
2005
May
, 8 (642-9).
Fournier C
et al.
Apamin improves reference memory but not procedural memory in rats by blocking small conductance Ca(2+)-activated K(+) channels in an olfactory discrimination task.
Behav. Brain Res.,
2001
Jun
, 121 (81-93).
Stackman RW
et al.
Small conductance Ca2+-activated K+ channels modulate synaptic plasticity and memory encoding.
J. Neurosci.,
2002
Dec
1
, 22 (10163-71).
Oliveira MS
et al.
Altered expression and function of small-conductance (SK) Ca(2+)-activated K+ channels in pilocarpine-treated epileptic rats.
Brain Res.,
2010
Aug
12
, 1348 (187-99).
Ishii TM
et al.
A human intermediate conductance calcium-activated potassium channel.
Proc. Natl. Acad. Sci. U.S.A.,
1997
Oct
14
, 94 (11651-6).
Maylie J
et al.
Small conductance Ca2+-activated K+ channels and calmodulin.
J. Physiol. (Lond.),
2004
Jan
15
, 554 (255-61).
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).
Allen D
et al.
The SK2-long isoform directs synaptic localization and function of SK2-containing channels.
Nat. Neurosci.,
2011
Jun
, 14 (744-9).
Contributors: Rajnish Ranjan, Michael Schartner
To cite this page: [Contributors] Channelpedia https://channelpedia.epfl.ch/wikipages/66/ , accessed on 2024 Dec 12