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Proc Natl Acad Sci U S A
2020 Oct 27;11743:27016-27021. doi: 10.1073/pnas.2007965117.
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Coupling stabilizers open KV1-type potassium channels.
Silverå Ejneby M
,
Wallner B
,
Elinder F
.
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The opening and closing of voltage-gated ion channels are regulated by voltage sensors coupled to a gate that controls the ion flux across the cellular membrane. Modulation of any part of gating constitutes an entry point for pharmacologically regulating channel function. Here, we report on the discovery of a large family of warfarin-like compounds that open the two voltage-gated type 1 potassium (KV1) channels KV1.5 and Shaker, but not the related KV2-, KV4-, or KV7-type channels. These negatively charged compounds bind in the open state to positively charged arginines and lysines between the intracellular ends of the voltage-sensor domains and the pore domain. This mechanism of action resembles that of endogenous channel-opening lipids and opens up an avenue for the development of ion-channel modulators.
Ahuja,
Structural basis of Nav1.7 inhibition by an isoform-selective small-molecule antagonist.
2015, Pubmed
Ahuja,
Structural basis of Nav1.7 inhibition by an isoform-selective small-molecule antagonist.
2015,
Pubmed
Börjesson,
Lipoelectric modification of ion channel voltage gating by polyunsaturated fatty acids.
2008,
Pubmed
,
Xenbase
Börjesson,
Electrostatic tuning of cellular excitability.
2010,
Pubmed
,
Xenbase
Börjesson,
An electrostatic potassium channel opener targeting the final voltage sensor transition.
2011,
Pubmed
,
Xenbase
Henrion,
Tracking a complete voltage-sensor cycle with metal-ion bridges.
2012,
Pubmed
,
Xenbase
Hille,
Local anesthetics: hydrophilic and hydrophobic pathways for the drug-receptor reaction.
1977,
Pubmed
Hoshi,
Biophysical and molecular mechanisms of Shaker potassium channel inactivation.
1990,
Pubmed
,
Xenbase
Jiang,
Structure of the Cardiac Sodium Channel.
2020,
Pubmed
Kamb,
Molecular characterization of Shaker, a Drosophila gene that encodes a potassium channel.
1987,
Pubmed
Kopljar,
The ladder-shaped polyether toxin gambierol anchors the gating machinery of Kv3.1 channels in the resting state.
2013,
Pubmed
Li,
The gating charge pathway of an epilepsy-associated potassium channel accommodates chemical ligands.
2013,
Pubmed
Liin,
Biaryl sulfonamide motifs up- or down-regulate ion channel activity by activating voltage sensors.
2018,
Pubmed
Liin,
Polyunsaturated fatty acids are potent openers of human M-channels expressed in Xenopus laevis oocytes.
2016,
Pubmed
,
Xenbase
Long,
Atomic structure of a voltage-dependent K+ channel in a lipid membrane-like environment.
2007,
Pubmed
Ottosson,
Resin-acid derivatives as potent electrostatic openers of voltage-gated K channels and suppressors of neuronal excitability.
2015,
Pubmed
,
Xenbase
Ottosson,
A drug pocket at the lipid bilayer-potassium channel interface.
2017,
Pubmed
Ottosson,
Drug-induced ion channel opening tuned by the voltage sensor charge profile.
2014,
Pubmed
,
Xenbase
Peretz,
Targeting the voltage sensor of Kv7.2 voltage-gated K+ channels with a new gating-modifier.
2010,
Pubmed
Ragsdale,
Molecular determinants of state-dependent block of Na+ channels by local anesthetics.
1994,
Pubmed
,
Xenbase
Schewe,
A pharmacological master key mechanism that unlocks the selectivity filter gate in K+ channels.
2019,
Pubmed
,
Xenbase
Silverå Ejneby,
Atom-by-atom tuning of the electrostatic potassium-channel modulator dehydroabietic acid.
2018,
Pubmed
,
Xenbase
Sun,
Structural Basis of Human KCNQ1 Modulation and Gating.
2020,
Pubmed
Swartz,
Hanatoxin modifies the gating of a voltage-dependent K+ channel through multiple binding sites.
1997,
Pubmed
,
Xenbase
Whitlon,
Mechanism of coumarin action: significance of vitamin K epoxide reductase inhibition.
1978,
Pubmed
Wisedchaisri,
Resting-State Structure and Gating Mechanism of a Voltage-Gated Sodium Channel.
2019,
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
Xiong,
Zinc pyrithione-mediated activation of voltage-gated KCNQ potassium channels rescues epileptogenic mutants.
2007,
Pubmed
Yang,
Structural mechanism underlying capsaicin binding and activation of the TRPV1 ion channel.
2015,
Pubmed
Zaydman,
Kv7.1 ion channels require a lipid to couple voltage sensing to pore opening.
2013,
Pubmed
,
Xenbase
Zhou,
Potassium channel receptor site for the inactivation gate and quaternary amine inhibitors.
2001,
Pubmed
,
Xenbase
