Channelpedia

SK2

Description: potassium intermediate/small conductance calcium-activated channel, subfamily N, member 2
Gene: Kcnn2
Alias: SK2, hSK2, SKCA2, KCa2.2, Kcnn2

Edit - History

Introduction

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].


Edit

Gene

Species NCBI gene ID Chromosome Position
Human 3781 5 440518
Mouse 140492 18 417200
Rat 54262 18 440381

Edit

Transcript

Species NCBI accession Length (nt)
Human NM_021614.4 2760
Mouse NM_001312905.2 3692
Rat NM_001309404.1 2069

Edit

Protein Isoforms

Species Uniprot ID Length (aa)
Human Q9H2S1 579
Mouse P58390 839
Rat P70604 580

Isoforms

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

Edit

Post-Translational Modifications

PTM
Position
Type

Edit - History

Structure

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

Species Area (Å2) Reference
Human 6063.37 source
Mouse 11927.49 source
Rat 8777.62 source

Methodology for AlphaFold size prediction and disclaimer are available here


Edit - History

Expression and Distribution

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].


Edit - History

CNS Sub-cellular Distribution

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].


Edit - History

Function

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].


Edit - History

Interaction

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

147

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).

150

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).

540

Orio P et al. New disguises for an old channel: MaxiK channel beta-subunits.
News Physiol. Sci., 2002 Aug , 17 (156-61).

541

543

545

546

Glowatzki E et al. Cholinergic synaptic inhibition of inner hair cells in the neonatal mammalian cochlea.
Science, 2000 Jun 30 , 288 (2366-8).

547

Schetz JA et al. Pharmacology of the high-affinity apamin receptor in rabbit heart.
Cardiovasc. Res., 1995 Nov , 30 (755-62).

549

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).

551

552

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).

554

Stackman RW et al. Small conductance Ca2+-activated K+ channels modulate synaptic plasticity and memory encoding.
J. Neurosci., 2002 Dec 1 , 22 (10163-71).

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).


Edit - History

Credits

Contributors: Rajnish Ranjan, Michael Schartner

To cite this page: [Contributors] Channelpedia https://channelpedia.epfl.ch/wikipages/66/ , accessed on 2024 Dec 12



Add section