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 ; Joiner
et al., 1998 ; Yuan et al., 2003 ). When expressed in heterologous
expression systems, Slick currents differ from Slack currents, in that
they exhibit instantaneous activation kinetics (Bhattacharjee et al.,
2003 ; Santi et al., 2006 ); Slack currents on the other hand exhibit slower activation kinetics in response to depolarization (Bhattacharjee et al., 2003 ; Joiner et al., 1998 ).
The gene Kcnt1 (also known as slo2; Slack; mKIAA1422; C030030G16Rik) encodes slo2, a potassium channel, subfamily T, member 1.
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.
The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.
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.
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 ). Slack and Slick contain
both overlapping and unique consensus PKC phosphorylation sites
(Bhattacharjee et al., 2003 ; Joiner et al., 1998 ) 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 ). Moreover, Slick and Slack channels were
colocalized with G-alpha-q–protein coupled receptors in certain neurons
(Santi et al., 2006 ) suggesting that PKC modulation is likely to also occur in native neurons. (Nuwer )
The homology between Slack
and Slick is high, especially within the putative six transmembrane
domains and proximal carboxy terminal (Bhattacharjee et al.,
2003 ). 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 ). The large carboxy termini of Slack, Slick and Slo contain "regulate the conductance of K+ (RCK) domains" (Bhattacharjee and Kaczmarek, 2005 ;
Salkoff et al., 2006 ). These RCK domains are thought to be essential
for ligand binding and concomitant gating for this class of potassium channel (Jiang et al., 2002 ; Ye et al., 2006 ).
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 .
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 , Bhattacharjee ). Interestingly, given the lack of
positive charges in S4, Slack channels are voltagedependent (Joiner ). 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 , Bhattacharjee ). The
kinetic properties of Slack channels suggest that they
could contribute to currents that develop slowly during
maintained neuronal firing. (Bhattacharjee