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potassium intermediate/small conductance calcium-activated channel, subfamily N, member 2
Synonyms: SK2 hSK2 SKCA2 KCa2.2 Kcnn2. Symbol: 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].


Kcnn2 : potassium intermediate/small conductance calcium-activated channel, subfamily N, member 2

RGD ID Chromosome Position Species
2963 18 39560962-39705037 Rat
734126 18 45719808-45845537 Mouse
734125 5 113698016-113832197 Human


Acc No Sequence Length Source
NM_019314 NCBI
NM_080465 NCBI
NM_021614 NCBI
NM_170775 NCBI


Accession Name Definition Evidence
GO:0016020 membrane Double layer of lipid molecules that encloses all cells, and, in eukaryotes, many organelles; may be a single or double lipid bilayer; also includes associated proteins. IEA
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. IDA



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]


The alkaloid methyl-laudanosine blocks SK1, SK2 and SK3 currents with equal potency, IK currents were unaffected. [143]



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]


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].


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].


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].




[149 : 18818242]
[150 : 17998394]
[141 : 17142458]
[151 : 17627990]
[152 : 16467533]
[142 : 15071101]
[144 : 14761961]
[145 : 14559917]
[153 : 14657188]
[146 : 14555714]
[539 : 16382103]
[540 : 12136044]
[541 : 10026195]
[542 : 9774106]
[543 : 11323678]
[143 : 15504758]
[545 : 11273646]
[544 : 10833304]
[547 : 8595623]
[548 : 6329722]
[147 : 11557517]
[549 : 228203]
[546 : 10875922]
[550 : 10200319]
[551 : 15852010]
[552 : 15852011]
[553 : 11275286]
[554 : 12451117]
[1459 : 18476673]
[1110 : 9326665]
[1112 : 14500775]
[1480 : 21602822]
[1479 : 15234350]
[1106 : 20553876]


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Contributors : Rajnish Ranjan, Michael Schartner

To cite : [Editor], [Contributors]. Accessed on [Date] Channelpedia ,