Channelpedia

SK1

Description: potassium intermediate/small conductance calcium-activated channel, subfamily N, member 1
Gene: Kcnn1     Synonyms: SK1, kcnn1

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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].


Experimental data


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Gene

RGD ID Chromosome Position Species
2962 - Rat
735814 8 73365948-73380907 Mouse
731634 19 18062111-18109930 Human

Kcnn1 : potassium intermediate/small conductance calcium-activated channel, subfamily N, member 1


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Transcript

Acc No Sequence Length Source
NM_019313 n/A n/A NCBI
NM_032397 n/A n/A NCBI
NM_002248 n/A n/A NCBI

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Ontology


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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]


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Protein


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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]


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Distribution

SK1 is frequently associated with neuronal fibers and only occasionally detected in neuronal somata. [1479]


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Expression

Central nervous system

SK channels are widely expressed in the central nervous system [544], [142]thereby potentially contributing to neuronal excitability control and they are critical regulators of neuronal excitability in hippocampus [1106]).

SK1 is expressed, from highest to lowest levels in: amígdala, hippocampus, caudate nucleus, cerebellum , thalamus, substantia nigra, spinal cord and pituitary gland. [539]. SK1 and SK2 are often expressed in the same neurons, predominantly in the neocortex, hippocampal formation, cerebellum, and thalamus [1479]).

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]).

Perpheral tissue [1482], [539]

SK1 is found in testis, ovary and aorta and in several pathological conditions such oligodendroglioma, glioblastoma and gastric tumour.


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Functional

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].


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Kinetics


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Model


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).

148

Shah M. et al. The pharmacology of hSK1 Ca2+-activated K+ channels expressed in mammalian cell lines.
Br. J. Pharmacol., 2000 Feb , 129 (627-30).

540

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

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).

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).

549

Jenkinson DH. et al. Apamin blocks certain neurotransmitter-induced increases in potassium permeability.
Nature, 1979 Nov 22 , 282 (415-7).

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).

552

Adelman JP. et al. SK channels and NMDA receptors form a Ca2+-mediated feedback loop in dendritic spines.
Nat. Neurosci., 2005 May , 8 (642-9).

1459

1112

Adelman JP. et al. Small conductance Ca2+-activated K+ channels and calmodulin.
J. Physiol. (Lond.), 2004 Jan 15 , 554 (255-61).


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Credits

Editor : Admin.

Contributors : Rajnish Ranjan, Michael Schartner

To cite : [Editor], [Contributors]. Accessed on [Date] Channelpedia , http://channelpedia.epfl.ch/ionchannels/65