Slo2
Description: potassium channel, subfamily T, member 1 Gene: Kcnt1 Alias: Slo2, kcnt1, KCa4.1, SLACK, KNa1.1, Slo2.2
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]).
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
Transcript
| Species | NCBI accession | Length (nt) | |
|---|---|---|---|
| Human | NM_020822.3 | 7123 | |
| Mouse | NM_175462.4 | 5987 | |
| Rat | NM_021853.1 | 3714 |
Protein Isoforms
Isoforms
Post-Translational Modifications
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
Methodology for AlphaFold size prediction and disclaimer are available here
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]
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].
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
Nuwer MO
et al.
cAMP-dependent kinase does not modulate the Slack sodium-activated potassium channel.
Neuropharmacology,
2009
Sep
, 57 (219-26).
Brown MR
et al.
Amino-termini isoforms of the Slack K+ channel, regulated by alternative promoters, differentially modulate rhythmic firing and adaptation.
J. Physiol. (Lond.),
2008
Nov
1
, 586 (5161-79).
Santi CM
et al.
Opposite regulation of Slick and Slack K+ channels by neuromodulators.
J. Neurosci.,
2006
May
10
, 26 (5059-68).
Yang B
et al.
Pharmacological activation and inhibition of Slack (Slo2.2) channels.
Neuropharmacology,
2006
Sep
, 51 (896-906).
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).
Joiner WJ
et al.
Formation of intermediate-conductance calcium-activated potassium channels by interaction of Slack and Slo subunits.
Nat. Neurosci.,
1998
Oct
, 1 (462-9).
Yuan A
et al.
The sodium-activated potassium channel is encoded by a member of the Slo gene family.
Neuron,
2003
Mar
6
, 37 (765-73).
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).
Ye S
et al.
Crystal structures of a ligand-free MthK gating ring: insights into the ligand gating mechanism of K+ channels.
Cell,
2006
Sep
22
, 126 (1161-73).
Credits
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