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J Neurosci
2004 Oct 13;2441:9146-52. doi: 10.1523/JNEUROSCI.3194-04.2004.
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Three mechanisms underlie KCNQ2/3 heteromeric potassium M-channel potentiation.
Etxeberria A
,
Santana-Castro I
,
Regalado MP
,
Aivar P
,
Villarroel A
.
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The non-inactivating potassium M-current exerts a strong influence on neuronal excitability. The channels responsible for this current are made up of KCNQ subunits, and mutations in most of these produce human pathologies. Notably, in terms of excitation, mutations in either KCNQ2 or KCNQ3 lead to benign neonatal familial convulsions. Although a mere reduction of 25% in KCNQ2/3 function can increase excitability to epileptogenic levels, the potentiation of these subunits has anti-epileptogenic effects. After KCNQ2/3 heteromerization, current levels can augment as much as 10-fold, and we have discovered that there are three processes underlying this potentiation. First, there is an increase in the number of channels inserted in the membrane after heteromerization of the C-terminal region. Second, the N-terminal domain from KCNQ2 exerts a negative influence on the current level. Finally, Ala 315 of KCNQ3, a residue located in the inner vestibule after the selectivity filter, plays a critical role in preventing current flow in KCNQ3 homomeric channels, whereas it is permissive in heteromers in combination with Thr at the equivalent 276 position of KCNQ2.
Alagem,
Mechanism of Ba(2+) block of a mouse inwardly rectifying K+ channel: differential contribution by two discrete residues.
2001, Pubmed,
Xenbase
Alagem,
Mechanism of Ba(2+) block of a mouse inwardly rectifying K+ channel: differential contribution by two discrete residues.
2001,
Pubmed
,
Xenbase
Biervert,
A potassium channel mutation in neonatal human epilepsy.
1998,
Pubmed
,
Xenbase
Bowie,
Inward rectification of both AMPA and kainate subtype glutamate receptors generated by polyamine-mediated ion channel block.
1995,
Pubmed
Brown,
Modulation and genetic identification of the M channel.
2000,
Pubmed
Chan,
Control of channel activity through a unique amino acid residue of a G protein-gated inwardly rectifying K+ channel subunit.
1996,
Pubmed
,
Xenbase
Dedek,
Myokymia and neonatal epilepsy caused by a mutation in the voltage sensor of the KCNQ2 K+ channel.
2001,
Pubmed
,
Xenbase
Doyle,
The structure of the potassium channel: molecular basis of K+ conduction and selectivity.
1998,
Pubmed
Greger,
AMPA receptor tetramerization is mediated by Q/R editing.
2003,
Pubmed
Gribkoff,
The therapeutic potential of neuronal KCNQ channel modulators.
2003,
Pubmed
,
Xenbase
Gutman,
International Union of Pharmacology. XLI. Compendium of voltage-gated ion channels: potassium channels.
2003,
Pubmed
Hadley,
Stoichiometry of expressed KCNQ2/KCNQ3 potassium channels and subunit composition of native ganglionic M channels deduced from block by tetraethylammonium.
2003,
Pubmed
Hübner,
Ion channel diseases.
2002,
Pubmed
Jentsch,
Neuronal KCNQ potassium channels: physiology and role in disease.
2000,
Pubmed
Kubisch,
KCNQ4, a novel potassium channel expressed in sensory outer hair cells, is mutated in dominant deafness.
1999,
Pubmed
,
Xenbase
Lerche,
A reduced K+ current due to a novel mutation in KCNQ2 causes neonatal convulsions.
1999,
Pubmed
,
Xenbase
Li,
Single-channel analysis of KCNQ K+ channels reveals the mechanism of augmentation by a cysteine-modifying reagent.
2004,
Pubmed
Ma,
ER transport signals and trafficking of potassium channels and receptors.
2002,
Pubmed
Maljevic,
C-terminal interaction of KCNQ2 and KCNQ3 K+ channels.
2003,
Pubmed
,
Xenbase
Manganas,
Identification of a trafficking determinant localized to the Kv1 potassium channel pore.
2001,
Pubmed
Marrion,
Control of M-current.
1997,
Pubmed
Mitcheson,
A structural basis for drug-induced long QT syndrome.
2000,
Pubmed
,
Xenbase
Neyroud,
A novel mutation in the potassium channel gene KVLQT1 causes the Jervell and Lange-Nielsen cardioauditory syndrome.
1997,
Pubmed
Prole,
Ionic permeation and conduction properties of neuronal KCNQ2/KCNQ3 potassium channels.
2004,
Pubmed
Schroeder,
Moderate loss of function of cyclic-AMP-modulated KCNQ2/KCNQ3 K+ channels causes epilepsy.
1998,
Pubmed
,
Xenbase
Schwake,
Surface expression and single channel properties of KCNQ2/KCNQ3, M-type K+ channels involved in epilepsy.
2000,
Pubmed
,
Xenbase
Schwake,
A carboxy-terminal domain determines the subunit specificity of KCNQ K+ channel assembly.
2003,
Pubmed
,
Xenbase
Seebohm,
Identification of specific pore residues mediating KCNQ1 inactivation. A novel mechanism for long QT syndrome.
2001,
Pubmed
,
Xenbase
Selyanko,
Properties of single M-type KCNQ2/KCNQ3 potassium channels expressed in mammalian cells.
2001,
Pubmed
Slesinger,
Ion selectivity filter regulates local anesthetic inhibition of G-protein-gated inwardly rectifying K+ channels.
2001,
Pubmed
,
Xenbase
Teasdale,
Signal-mediated sorting of membrane proteins between the endoplasmic reticulum and the golgi apparatus.
1996,
Pubmed
Villarroel,
Inhibition of the Kv4 (Shal) family of transient K+ currents by arachidonic acid.
1996,
Pubmed
,
Xenbase
Wang,
Positional cloning of a novel potassium channel gene: KVLQT1 mutations cause cardiac arrhythmias.
1996,
Pubmed
Wang,
KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel.
1998,
Pubmed
,
Xenbase
Yellen,
Mutations affecting internal TEA blockade identify the probable pore-forming region of a K+ channel.
1991,
Pubmed
Yifrach,
Energetics of pore opening in a voltage-gated K(+) channel.
2002,
Pubmed
,
Xenbase
Yus-Najera,
The identification and characterization of a noncontinuous calmodulin-binding site in noninactivating voltage-dependent KCNQ potassium channels.
2002,
Pubmed
Zhou,
Mutations in the pore region of ROMK enhance Ba2+ block.
1996,
Pubmed
,
Xenbase
Zhu,
Determinants involved in Kv1 potassium channel folding in the endoplasmic reticulum, glycosylation in the Golgi, and cell surface expression.
2001,
Pubmed
