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.
Commun Biol
2020 Feb 28;31:90. doi: 10.1038/s42003-020-0820-9.
Show Gene links
Show Anatomy links
Potassium channels act as chemosensors for solute transporters.
Manville RW
,
Abbott GW
.
???displayArticle.abstract???
Potassium channels form physical complexes with solute transporters in vivo, yet little is known about their range of possible signaling modalities and the underlying mechanisms. The KCNQ2/3 potassium channel, which generates neuronal M-current, is voltage-gated and its activity is also stimulated by binding of various small molecules. KCNQ2/3 forms reciprocally regulating complexes with sodium-coupled myo-inositol transporters (SMITs) in mammalian neurons. Here, we report that the neurotransmitter γ-aminobutyric acid (GABA) and other small molecules directly regulate myo-inositol transport in rat dorsal root ganglia, and by human SMIT1-KCNQ2/3 complexes in vitro, by inducing a distinct KCNQ2/3 pore conformation. Reciprocally, SMIT1 tunes KCNQ2/3 sensing of GABA and related metabolites. Ion permeation and mutagenesis studies suggest that SMIT1 and GABA similarly alter KCNQ2/3 pore conformation but via different KCNQ subunits and molecular mechanisms. KCNQ channels therefore act as chemosensors to enable co-assembled myo-inositol transporters to respond to diverse stimuli including neurotransmitters, metabolites and drugs.
Abbott,
KCNQ1, KCNE2, and Na+-coupled solute transporters form reciprocally regulating complexes that affect neuronal excitability.
2014, Pubmed,
Xenbase
Abbott,
KCNQ1, KCNE2, and Na+-coupled solute transporters form reciprocally regulating complexes that affect neuronal excitability.
2014,
Pubmed
,
Xenbase
Andrade,
A G protein couples serotonin and GABAB receptors to the same channels in hippocampus.
1986,
Pubmed
Baronas,
Slc7a5 regulates Kv1.2 channels and modifies functional outcomes of epilepsy-linked channel mutations.
2018,
Pubmed
Bartolomé-Martín,
Identification of potassium channel proteins Kv7.2/7.3 as common partners of the dopamine and glutamate transporters DAT and GLT-1.
2019,
Pubmed
Biervert,
A potassium channel mutation in neonatal human epilepsy.
1998,
Pubmed
,
Xenbase
Brown,
Muscarinic suppression of a novel voltage-sensitive K+ current in a vertebrate neurone.
1980,
Pubmed
Cooper,
M channel KCNQ2 subunits are localized to key sites for control of neuronal network oscillations and synchronization in mouse brain.
2001,
Pubmed
De Silva,
Deconstruction of an African folk medicine uncovers a novel molecular strategy for therapeutic potassium channel activation.
2018,
Pubmed
,
Xenbase
Etxeberria,
Three mechanisms underlie KCNQ2/3 heteromeric potassium M-channel potentiation.
2004,
Pubmed
,
Xenbase
Johansson,
Defining and searching for structural motifs using DeepView/Swiss-PdbViewer.
2012,
Pubmed
Kim,
The Voltage Activation of Cortical KCNQ Channels Depends on Global PIP2 Levels.
2016,
Pubmed
Klinger,
Distribution of M-channel subunits KCNQ2 and KCNQ3 in rat hippocampus.
2011,
Pubmed
Loussouarn,
Phosphatidylinositol-4,5-bisphosphate, PIP2, controls KCNQ1/KCNE1 voltage-gated potassium channels: a functional homology between voltage-gated and inward rectifier K+ channels.
2003,
Pubmed
Manville,
Direct neurotransmitter activation of voltage-gated potassium channels.
2018,
Pubmed
,
Xenbase
Manville,
SMIT1 Modifies KCNQ Channel Function and Pharmacology by Physical Interaction with the Pore.
2017,
Pubmed
Manville,
Ancient and modern anticonvulsants act synergistically in a KCNQ potassium channel binding pocket.
2018,
Pubmed
,
Xenbase
Manville,
Cilantro leaf harbors a potent potassium channel-activating anticonvulsant.
2019,
Pubmed
,
Xenbase
Manville,
KCNQ5 activation is a unifying molecular mechanism shared by genetically and culturally diverse botanical hypotensive folk medicines.
2019,
Pubmed
Manville,
Teamwork: Ion channels and transporters join forces in the brain.
2019,
Pubmed
Manville,
M-Channel Activation Contributes to the Anticonvulsant Action of the Ketone Body β-Hydroxybutyrate.
2020,
Pubmed
,
Xenbase
Martire,
M channels containing KCNQ2 subunits modulate norepinephrine, aspartate, and GABA release from hippocampal nerve terminals.
2004,
Pubmed
Neverisky,
KCNQ-SMIT complex formation facilitates ion channel-solute transporter cross talk.
2017,
Pubmed
,
Xenbase
Pan,
Human brain beta-hydroxybutyrate and lactate increase in fasting-induced ketosis.
2000,
Pubmed
Park,
Drosophila SLC5A11 Mediates Hunger by Regulating K(+) Channel Activity.
2016,
Pubmed
Peretz,
Pre- and postsynaptic activation of M-channels by a novel opener dampens neuronal firing and transmitter release.
2007,
Pubmed
Pettersen,
UCSF Chimera--a visualization system for exploratory research and analysis.
2004,
Pubmed
Sigel,
Structure, function, and modulation of GABA(A) receptors.
2012,
Pubmed
Singh,
A novel potassium channel gene, KCNQ2, is mutated in an inherited epilepsy of newborns.
1998,
Pubmed
Singh,
MaxiK channel interactome reveals its interaction with GABA transporter 3 and heat shock protein 60 in the mammalian brain.
2016,
Pubmed
Splinter,
Efficacy of retigabine in adjunctive treatment of partial onset seizures in adults.
2013,
Pubmed
Suh,
Electrostatic interaction of internal Mg2+ with membrane PIP2 Seen with KCNQ K+ channels.
2007,
Pubmed
Suh,
PIP2 is a necessary cofactor for ion channel function: how and why?
2008,
Pubmed
Sun,
Cryo-EM Structure of a KCNQ1/CaM Complex Reveals Insights into Congenital Long QT Syndrome.
2017,
Pubmed
,
Xenbase
Uchida,
Abnormal γ-aminobutyric acid neurotransmission in a Kcnq2 model of early onset epilepsy.
2017,
Pubmed
Wang,
KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel.
1998,
Pubmed
,
Xenbase
