Channelpedia

Slo2

Description: potassium channel, subfamily T, member 1
Gene: Kcnt1
Alias: Slo2, kcnt1, KCa4.1, SLACK, KNa1.1, Slo2.2

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Introduction

Two genes, Slack (also known as kcnt1 or Slo2.2) and Slick (also known as kcnt 2 or Slo 2.1) encode outwardly rectifying potassium channels that are activated by intracellular Na+ (Bhattacharjee et al., 2003 [1137]; Joiner et al., 1998 [1138]; Yuan et al., 2003 [1139]). When expressed in heterologous expression systems, Slick currents differ from Slack currents, in that they exhibit instantaneous activation kinetics (Bhattacharjee et al., 2003 [1137]; Santi et al., 2006 [161]); Slack currents on the other hand exhibit slower activation kinetics in response to depolarization (Bhattacharjee et al., 2003 [1137]; Joiner et al., 1998 [1138]).


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Gene

The gene Kcnt1 (also known as slo2; Slack; mKIAA1422; C030030G16Rik) encodes slo2, a potassium channel, subfamily T, member 1. http://www.ncbi.nlm.nih.gov/gene/227632

Species NCBI gene ID Chromosome Position
Human 57582 9 93317
Mouse 227632 2 54478
Rat 60444 3 53651

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Transcript

Species NCBI accession Length (nt)
Human NM_020822.3 7123
Mouse NM_175462.4 5987
Rat NM_021853.1 3714

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Protein Isoforms

Species Uniprot ID Length (aa)
Human Q5JUK3 1230
Mouse Q6ZPR4 1224
Rat Q9Z258 1237

Isoforms

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

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Post-Translational Modifications

PTM
Position
Type

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Structure

The homology between Slack and Slick is high, especially within the putative six transmembrane domains and proximal carboxy terminal (Bhattacharjee et al., 2003 [1141]). Both channels resemble the Ca2+-activated K+ ‘Slowpoke’ (Slo) channel by containing very large carboxy termini in addition to the transmembrane domains (Salkoff et al., 2006 [1140]). The large carboxy termini of Slack, Slick and Slo contain "regulate the conductance of K+ (RCK) domains" (Bhattacharjee and Kaczmarek, 2005 [1137]; Salkoff et al., 2006 [1140]). These RCK domains are thought to be essential for ligand binding and concomitant gating for this class of potassium channel (Jiang et al., 2002 [625]; Ye et al., 2006 [1142]).

Slo2 predicted AlphaFold size

Species Area (Å2) Reference
Human 6931.39 source
Mouse 8188.77 source
Rat 7712.45 source

Methodology for AlphaFold size prediction and disclaimer are available here


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Kinetics

In symmetrical KC conditions, Slack channels have an EC50 of 41 mM for activation by Na+ and a unitary conductance of 180 pS, with multiple subconductance states (Yuan [1139], Bhattacharjee [1141]). Interestingly, given the lack of positive charges in S4, Slack channels are voltagedependent (Joiner [1138]). Slack currents are outwardly rectifying and, in response to depolarization, they typically have an instantaneous component followed by a slow time-dependent increase in current (i.e. a ‘slow-gate’) (Joiner [1138], Bhattacharjee [1141]). The kinetic properties of Slack channels suggest that they could contribute to currents that develop slowly during maintained neuronal firing. (Bhattacharjee [1137]


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Expression and Distribution

Slo2 is widely expressed in the rat brain. For a detailed table about the expression of Slo2 (Slack) see table 1 in Bhattacharjee and Kaczmarek, 2005 [1137].


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Interaction

Both Slack and Slick have numerous consensus phosphorylation sites within their respective carboxy termini and modulation of Na+ binding and subsequent gating could be feasible through phosphorylation or dephosphorylation-induced conformational changes. Indeed, the modulation of Slack and Slick by protein kinase C (PKC) has previously been determined (Santi et al., 2006 [1139]). Slack and Slick contain both overlapping and unique consensus PKC phosphorylation sites (Bhattacharjee et al., 2003 [1141]; Joiner et al., 1998 [1138]) and it was shown that activation of PKC by phorbol esters caused an inhibition of Slick currents whereas Slack currents were facilitated after PKC activation (Santi et al., 2006 [1139]). Moreover, Slick and Slack channels were colocalized with G-alpha-q–protein coupled receptors in certain neurons (Santi et al., 2006 [1139]) suggesting that PKC modulation is likely to also occur in native neurons. (Nuwer [159])


References

159

Nuwer MO et al. cAMP-dependent kinase does not modulate the Slack sodium-activated potassium channel.
Neuropharmacology, 2009 Sep , 57 (219-26).

161

Santi CM et al. Opposite regulation of Slick and Slack K+ channels by neuromodulators.
J. Neurosci., 2006 May 10 , 26 (5059-68).

162

Yang B et al. Pharmacological activation and inhibition of Slack (Slo2.2) channels.
Neuropharmacology, 2006 Sep , 51 (896-906).

625

Jiang Y et al. Crystal structure and mechanism of a calcium-gated potassium channel.
Nature, 2002 May 30 , 417 (515-22).

Bhattacharjee A et al. For K+ channels, Na+ is the new Ca2+.
Trends Neurosci., 2005 Aug , 28 (422-8).

Salkoff L et al. High-conductance potassium channels of the SLO family.
Nat. Rev. Neurosci., 2006 Dec , 7 (921-31).

Bhattacharjee A et al. Slick (Slo2.1), a rapidly-gating sodium-activated potassium channel inhibited by ATP.
J. Neurosci., 2003 Dec 17 , 23 (11681-91).


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Credits

To cite this page: [Contributors] Channelpedia https://channelpedia.epfl.ch/wikipages/69/ , accessed on 2024 Nov 21



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