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.
The ubiquitous flavonoid quercetin is an atypical KCNQ potassium channel activator.
Redford KE
,
Abbott GW
.
???displayArticle.abstract???
Many commonly consumed plants are used as folk medicines, often with unclear molecular mechanisms. Recent studies uncovered the ubiquitous and influential KCNQ family of voltage-gated potassium (Kv) channels as a therapeutic target for several medicinal plant compounds. Capers - immature flower buds of Capparis spinosa - have been consumed for food and medicinal purposes for millennia. Here, we show that caper extract hyperpolarizes cells expressing KCNQ1 or KCNQ2/3 Kv channels. Capers are the richest known natural source of quercetin, the most consumed dietary flavonoid. Quercetin potentiated KCNQ1/KCNE1, KCNQ2/3 and KCNQ4 currents but, unusually, not KCNQ5. Strikingly, quercetin augmented both activation and inactivation of KCNQ1, via a unique KCNQ activation mechanism involving sites atop the voltage sensor and in the pore. The findings uncover a novel potential molecular basis for therapeutic effects of quercetin-rich foods and a new chemical space for atypical modes of KCNQ channel modulation.
Barhanin,
K(V)LQT1 and lsK (minK) proteins associate to form the I(Ks) cardiac potassium current.
1996, Pubmed,
Xenbase
Barhanin,
K(V)LQT1 and lsK (minK) proteins associate to form the I(Ks) cardiac potassium current.
1996,
Pubmed
,
Xenbase
Biervert,
A potassium channel mutation in neonatal human epilepsy.
1998,
Pubmed
,
Xenbase
Cowley,
Characterization of basolateral K+ channels underlying anion secretion in the human airway cell line Calu-3.
2002,
Pubmed
Cuthbert,
Mechanisms of anion secretion in Calu-3 human airway epithelial cells by 7,8-benzoquinoline.
2003,
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
Formica,
Review of the biology of Quercetin and related bioflavonoids.
1995,
Pubmed
Grosdidier,
SwissDock, a protein-small molecule docking web service based on EADock DSS.
2011,
Pubmed
Grosdidier,
Fast docking using the CHARMM force field with EADock DSS.
2011,
Pubmed
Hardy,
Neanderthal medics? Evidence for food, cooking, and medicinal plants entrapped in dental calculus.
2012,
Pubmed
Harwood,
A critical review of the data related to the safety of quercetin and lack of evidence of in vivo toxicity, including lack of genotoxic/carcinogenic properties.
2007,
Pubmed
Hille,
Ion channels: from idea to reality.
1999,
Pubmed
Jiang,
The discovery of Capparis spinosa L. (Capparidaceae) in the Yanghai Tombs (2800 years b.p.), NW China, and its medicinal implications.
2007,
Pubmed
Kang,
Structure of KCNE1 and implications for how it modulates the KCNQ1 potassium channel.
2008,
Pubmed
Kim,
Atomic basis for therapeutic activation of neuronal potassium channels.
2015,
Pubmed
,
Xenbase
Klinger,
Distribution of M-channel subunits KCNQ2 and KCNQ3 in rat hippocampus.
2011,
Pubmed
Kroncke,
Structural basis for KCNE3 modulation of potassium recycling in epithelia.
2016,
Pubmed
Kubisch,
KCNQ4, a novel potassium channel expressed in sensory outer hair cells, is mutated in dominant deafness.
1999,
Pubmed
,
Xenbase
Lange,
Refinement of the binding site and mode of action of the anticonvulsant Retigabine on KCNQ K+ channels.
2009,
Pubmed
,
Xenbase
Main,
Modulation of KCNQ2/3 potassium channels by the novel anticonvulsant retigabine.
2000,
Pubmed
,
Xenbase
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,
In silico re-engineering of a neurotransmitter to activate KCNQ potassium channels in an isoform-specific manner.
2019,
Pubmed
,
Xenbase
Manville,
Gabapentin Is a Potent Activator of KCNQ3 and KCNQ5 Potassium Channels.
2018,
Pubmed
,
Xenbase
Manville,
Direct neurotransmitter activation of voltage-gated potassium channels.
2018,
Pubmed
,
Xenbase
Manville,
M-Channel Activation Contributes to the Anticonvulsant Action of the Ketone Body β-Hydroxybutyrate.
2020,
Pubmed
,
Xenbase
Matschke,
The Natural Plant Product Rottlerin Activates Kv7.1/KCNE1 Channels.
2016,
Pubmed
,
Xenbase
Melamed,
The plant component of an Acheulian diet at Gesher Benot Ya'aqov, Israel.
2016,
Pubmed
Notas,
Quercetin accumulates in nuclear structures and triggers specific gene expression in epithelial cells.
2012,
Pubmed
Panaghie,
The role of S4 charges in voltage-dependent and voltage-independent KCNQ1 potassium channel complexes.
2007,
Pubmed
,
Xenbase
Panaghie,
Voltage-dependent C-type inactivation in a constitutively open K+ channel.
2008,
Pubmed
,
Xenbase
Panaghie,
Interaction of KCNE subunits with the KCNQ1 K+ channel pore.
2006,
Pubmed
,
Xenbase
Pusch,
Activation and inactivation of homomeric KvLQT1 potassium channels.
1998,
Pubmed
,
Xenbase
Sanguinetti,
Coassembly of K(V)LQT1 and minK (IsK) proteins to form cardiac I(Ks) potassium channel.
1996,
Pubmed
,
Xenbase
Schenzer,
Molecular determinants of KCNQ (Kv7) K+ channel sensitivity to the anticonvulsant retigabine.
2005,
Pubmed
,
Xenbase
Schroeder,
A constitutively open potassium channel formed by KCNQ1 and KCNE3.
2000,
Pubmed
,
Xenbase
Sesti,
Single-channel characteristics of wild-type IKs channels and channels formed with two minK mutants that cause long QT syndrome.
1998,
Pubmed
,
Xenbase
Singh,
A novel potassium channel gene, KCNQ2, is mutated in an inherited epilepsy of newborns.
1998,
Pubmed
Sun,
Structural Basis of Human KCNQ1 Modulation and Gating.
2020,
Pubmed
Sun,
Characterization and structure-activity relationship of natural flavonoids as hERG K+ channel modulators.
2017,
Pubmed
Tatulian,
Activation of expressed KCNQ potassium currents and native neuronal M-type potassium currents by the anti-convulsant drug retigabine.
2001,
Pubmed
Tristani-Firouzi,
Voltage-dependent inactivation of the human K+ channel KvLQT1 is eliminated by association with minimal K+ channel (minK) subunits.
1998,
Pubmed
,
Xenbase
Tyson,
IsK and KvLQT1: mutation in either of the two subunits of the slow component of the delayed rectifier potassium channel can cause Jervell and Lange-Nielsen syndrome.
1997,
Pubmed
Tzingounis,
The KCNQ5 potassium channel mediates a component of the afterhyperpolarization current in mouse hippocampus.
2010,
Pubmed
,
Xenbase
Vetter,
Inner ear defects induced by null mutation of the isk gene.
1996,
Pubmed
Wang,
KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel.
1998,
Pubmed
,
Xenbase
Weyrich,
Neanderthal behaviour, diet, and disease inferred from ancient DNA in dental calculus.
2017,
Pubmed
Wickenden,
Retigabine, a novel anti-convulsant, enhances activation of KCNQ2/Q3 potassium channels.
2000,
Pubmed
Wuttke,
The new anticonvulsant retigabine favors voltage-dependent opening of the Kv7.2 (KCNQ2) channel by binding to its activation gate.
2005,
Pubmed
,
Xenbase
Yeung,
Molecular expression and pharmacological identification of a role for K(v)7 channels in murine vascular reactivity.
2007,
Pubmed
