Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Cell Rep
2016 Jan 05;141:129-139. doi: 10.1016/j.celrep.2015.12.019.
Show Gene links
Show Anatomy links
Epilepsy-Related Slack Channel Mutants Lead to Channel Over-Activity by Two Different Mechanisms.
Tang QY
,
Zhang FF
,
Xu J
,
Wang R
,
Chen J
,
Logothetis DE
,
Zhang Z
.
???displayArticle.abstract???
Twelve sodium-activated potassium channel (KCNT1, Slack) genetic mutants have been identified from severe early-onset epilepsy patients. The changes in biophysical properties of these mutants and the underlying mechanisms causing disease remain elusive. Here, we report that seven of the 12 mutations increase, whereas one mutation decreases, the channel's sodium sensitivity. Two of the mutants exhibit channel over-activity only when the intracellular Na(+) ([Na(+)]i) concentration is ∼80 mM. In contrast, single-channel data reveal that all 12 mutants increase the maximal open probability (Po). We conclude that these mutant channels lead to channel over-activity predominantly by increasing the ability of sodium binding to activate the channel, which is indicated by its maximal Po. The sodium sensitivity of these epilepsy causing mutants probably determines the [Na(+)]i concentration at which these mutants exert their pathological effects.
Barcia,
De novo gain-of-function KCNT1 channel mutations cause malignant migrating partial seizures of infancy.
2012, Pubmed,
Xenbase
Barcia,
De novo gain-of-function KCNT1 channel mutations cause malignant migrating partial seizures of infancy.
2012,
Pubmed
,
Xenbase
Bhattacharjee,
Localization of the Na+-activated K+ channel Slick in the rat central nervous system.
2005,
Pubmed
Bhattacharjee,
For K+ channels, Na+ is the new Ca2+.
2005,
Pubmed
Bhattacharjee,
Localization of the Slack potassium channel in the rat central nervous system.
2002,
Pubmed
Brew,
Seizures and reduced life span in mice lacking the potassium channel subunit Kv1.2, but hypoexcitability and enlarged Kv1 currents in auditory neurons.
2007,
Pubmed
Brown,
Amino-termini isoforms of the Slack K+ channel, regulated by alternative promoters, differentially modulate rhythmic firing and adaptation.
2008,
Pubmed
,
Xenbase
Brown,
Fragile X mental retardation protein controls gating of the sodium-activated potassium channel Slack.
2010,
Pubmed
Callaway,
Spatial distribution of synaptically activated sodium concentration changes in cerebellar Purkinje neurons.
1997,
Pubmed
Colquhoun,
Binding, gating, affinity and efficacy: the interpretation of structure-activity relationships for agonists and of the effects of mutating receptors.
1998,
Pubmed
D'Adamo,
K(+) channelepsy: progress in the neurobiology of potassium channels and epilepsy.
2013,
Pubmed
Du,
Calcium-sensitive potassium channelopathy in human epilepsy and paroxysmal movement disorder.
2005,
Pubmed
,
Xenbase
Egan,
Na(+)-activated K+ channels are widely distributed in rat CNS and in Xenopus oocytes.
1992,
Pubmed
,
Xenbase
Fekete,
Mechanism of the persistent sodium current activator veratridine-evoked Ca elevation: implication for epilepsy.
2009,
Pubmed
Fisher,
Epileptic seizures and epilepsy: definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE).
2005,
Pubmed
Gao,
Slack and Slick KNa channels are required for the depolarizing afterpotential of acutely isolated, medium diameter rat dorsal root ganglion neurons.
2008,
Pubmed
Hage,
Sodium-activated potassium channels are functionally coupled to persistent sodium currents.
2012,
Pubmed
Heron,
Missense mutations in the sodium-gated potassium channel gene KCNT1 cause severe autosomal dominant nocturnal frontal lobe epilepsy.
2012,
Pubmed
Huang,
TMEM16C facilitates Na(+)-activated K+ currents in rat sensory neurons and regulates pain processing.
2013,
Pubmed
Ishii,
A recurrent KCNT1 mutation in two sporadic cases with malignant migrating partial seizures in infancy.
2013,
Pubmed
Jiang,
The open pore conformation of potassium channels.
2002,
Pubmed
Jiang,
Crystal structure and mechanism of a calcium-gated potassium channel.
2002,
Pubmed
Joiner,
Formation of intermediate-conductance calcium-activated potassium channels by interaction of Slack and Slo subunits.
1998,
Pubmed
Joshi,
Higher gamma-aminobutyric acid neuron density in the white matter of orbital frontal cortex in schizophrenia.
2012,
Pubmed
Kameyama,
Intracellular Na+ activates a K+ channel in mammalian cardiac cells.
,
Pubmed
Kim,
Emerging role of the KCNT1 Slack channel in intellectual disability.
2014,
Pubmed
Kim,
Human slack potassium channel mutations increase positive cooperativity between individual channels.
2014,
Pubmed
,
Xenbase
Kleinhans,
Multi-photon intracellular sodium imaging combined with UV-mediated focal uncaging of glutamate in CA1 pyramidal neurons.
2014,
Pubmed
Lossin,
Epilepsy-associated dysfunction in the voltage-gated neuronal sodium channel SCN1A.
2003,
Pubmed
Lu,
The neuronal channel NALCN contributes resting sodium permeability and is required for normal respiratory rhythm.
2007,
Pubmed
,
Xenbase
Mittmann,
Evidence for persistent Na+ current in apical dendrites of rat neocortical neurons from imaging of Na+-sensitive dye.
1997,
Pubmed
Müller,
Na(+) and K(+) concentrations, extra- and intracellular voltages, and the effect of TTX in hypoxic rat hippocampal slices.
2000,
Pubmed
Niu,
Linker-gating ring complex as passive spring and Ca(2+)-dependent machine for a voltage- and Ca(2+)-activated potassium channel.
2004,
Pubmed
,
Xenbase
Rose,
Two sides of the same coin: sodium homeostasis and signaling in astrocytes under physiological and pathophysiological conditions.
2013,
Pubmed
Salkoff,
High-conductance potassium channels of the SLO family.
2006,
Pubmed
Smart,
Deletion of the K(V)1.1 potassium channel causes epilepsy in mice.
1998,
Pubmed
Soumier,
Opposing effects of acute versus chronic blockade of frontal cortex somatostatin-positive inhibitory neurons on behavioral emotionality in mice.
2014,
Pubmed
Tamsett,
NAD+ activates KNa channels in dorsal root ganglion neurons.
2009,
Pubmed
Tang,
Structural determinants of phosphatidylinositol 4,5-bisphosphate (PIP2) regulation of BK channel activity through the RCK1 Ca2+ coordination site.
2014,
Pubmed
Tang,
Phosphatidylinositol 4,5-bisphosphate activates Slo3 currents and its hydrolysis underlies the epidermal growth factor-induced current inhibition.
2010,
Pubmed
,
Xenbase
Vanderver,
Identification of a novel de novo p.Phe932Ile KCNT1 mutation in a patient with leukoencephalopathy and severe epilepsy.
2014,
Pubmed
Wang,
Functional analysis of potassium channels in Kv7.2 G271V mutant causing early onset familial epilepsy.
2015,
Pubmed
Whorton,
Crystal structure of the mammalian GIRK2 K+ channel and gating regulation by G proteins, PIP2, and sodium.
2011,
Pubmed
,
Xenbase
Wu,
Structure of the gating ring from the human large-conductance Ca(2+)-gated K(+) channel.
2010,
Pubmed
Yang,
Slack and Slick K(Na) channels regulate the accuracy of timing of auditory neurons.
2007,
Pubmed
Yang,
An epilepsy/dyskinesia-associated mutation enhances BK channel activation by potentiating Ca2+ sensing.
2010,
Pubmed
,
Xenbase
Yu,
Reduced sodium current in GABAergic interneurons in a mouse model of severe myoclonic epilepsy in infancy.
2006,
Pubmed
Yuan,
Structure of the human BK channel Ca2+-activation apparatus at 3.0 A resolution.
2010,
Pubmed
Yuan,
The sodium-activated potassium channel is encoded by a member of the Slo gene family.
2003,
Pubmed
,
Xenbase
Zeng,
SLO3 auxiliary subunit LRRC52 controls gating of sperm KSPER currents and is critical for normal fertility.
2015,
Pubmed
Zhang,
SLO-2 isoforms with unique Ca(2+) - and voltage-dependence characteristics confer sensitivity to hypoxia in C. elegans.
2013,
Pubmed
Zhang,
The RCK2 domain uses a coordination site present in Kir channels to confer sodium sensitivity to Slo2.2 channels.
2010,
Pubmed
,
Xenbase
Zhang,
Regulation of neuronal excitability by interaction of fragile X mental retardation protein with slack potassium channels.
2012,
Pubmed
de los Angeles Tejada,
PIP₂ modulation of Slick and Slack K⁺ channels.
2012,
Pubmed
,
Xenbase
