SK1
Description: potassium intermediate/small conductance calcium-activated channel, subfamily N, member 1 Gene: Kcnn1 Alias: SK1, kcnn1, KCa2.1
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
Rat SK1 gene in CHO host cells |
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Gene
Transcript
| Species | NCBI accession | Length (nt) | |
|---|---|---|---|
| Human | NM_002248.5 | 3633 | |
| Mouse | NM_001363407.1 | 3270 | |
| Rat | NM_019313.1 | 1611 |
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]
SK1 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 [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.
SK1 is frequently associated with neuronal fibers and only occasionally detected in neuronal somata. [1479]
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
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An amino acid outside the pore region influences apamin sensitivity in small conductance Ca2+-activated K+ channels.
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SKCa channels mediate the medium but not the slow calcium-activated afterhyperpolarization in cortical neurons.
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Electrophysiological characterization of the SK channel blockers methyl-laudanosine and methyl-noscapine in cell lines and rat brain slices.
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The SK3 subunit of small conductance Ca2+-activated K+ channels interacts with both SK1 and SK2 subunits in a heterologous expression system.
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Small conductance Ca2+-activated K+ channels formed by the expression of rat SK1 and SK2 genes in HEK 293 cells.
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Developmental expression of the small-conductance Ca(2+)-activated potassium channel SK2 in the rat retina.
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Cholinergic synaptic inhibition of inner hair cells in the neonatal mammalian cochlea.
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SK channels regulate excitatory synaptic transmission and plasticity in the lateral amygdala.
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, 8 (635-41).
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SK channels and NMDA receptors form a Ca2+-mediated feedback loop in dendritic spines.
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Apamin improves reference memory but not procedural memory in rats by blocking small conductance Ca(2+)-activated K(+) channels in an olfactory discrimination task.
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Small conductance Ca2+-activated K+ channels modulate synaptic plasticity and memory encoding.
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, 22 (10163-71).
Oliveira MS
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Altered expression and function of small-conductance (SK) Ca(2+)-activated K+ channels in pilocarpine-treated epileptic rats.
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Maylie J
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Small conductance Ca2+-activated K+ channels and calmodulin.
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K+ channel modulators for the treatment of neurological disorders and autoimmune diseases.
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Sailer CA
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Comparative immunohistochemical distribution of three small-conductance Ca2+-activated potassium channel subunits, SK1, SK2, and SK3 in mouse brain.
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Contributors: Rajnish Ranjan, Michael Schartner
To cite this page: [Contributors] Channelpedia https://channelpedia.epfl.ch/wikipages/65/ , accessed on 2024 Apr 19