Source:http://linkedlifedata.com/resource/pubmed/id/16904708
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
6
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| pubmed:dateCreated |
2006-11-6
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| pubmed:abstractText |
The family of Kv7 (KCNQ) potassium channels consists of five members. Kv7.2 and 3 are the primary molecular correlates of the M-current, but also Kv7.4 and Kv7.5 display M-current characteristics. M-channel modulators include blockers (e.g., linopirdine) for cognition enhancement and openers (e.g., retigabine) for treatment of epilepsy and neuropathic pain. We investigated the effect of a Bristol-Myers Squibb compound (S)-N-[1-(3-morpholin-4-yl-phenyl)-ethyl]-3-phenyl-acrylamide [(S)-1] on cloned human Kv7.1-5 potassium channels expressed in Xenopus laevis oocytes. Using two-electrode voltage-clamp recordings we found that (S)-1 blocks Kv7.1 and Kv7.1/KCNE1 currents. In contrast, (S)-1 produced a hyperpolarizing shift of the activation curve for Kv7.2, Kv7.2/Kv7.3, Kv7.4 and Kv7.5. Further, the compound enhanced the maximal current amplitude at all potentials for Kv7.4 and Kv7.5 whereas the combined activation/block of Kv7.2 and Kv7.2/3 was strongly voltage-dependent. The tryptophan residue 242 in S5, known to be crucial for the effect of retigabine, was also shown to be critical for the enhancing effect of (S)-1 and BMS204352. Furthermore, no additive effect on Kv7.4 current amplitude was observed when both retigabine and (S)-1 or BMS204352 were applied simultaneously. In conclusion, (S)-1 differentially affects the Kv7 channel subtypes and is dependent on a single tryptophan for the current enhancing effect in Kv7.4.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Acrylamides,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/KCNQ Potassium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/KCNQ1 Potassium Channel,
http://linkedlifedata.com/resource/pubmed/chemical/KCNQ2 Potassium Channel,
http://linkedlifedata.com/resource/pubmed/chemical/KCNQ4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Morpholines,
http://linkedlifedata.com/resource/pubmed/chemical/N-(1-(3-morpholin-4-ylphenyl)ethyl)-...,
http://linkedlifedata.com/resource/pubmed/chemical/Tryptophan
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| pubmed:status |
MEDLINE
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| pubmed:month |
Nov
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| pubmed:issn |
0028-3908
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
51
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1068-77
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| pubmed:meshHeading |
pubmed-meshheading:16904708-Acrylamides,
pubmed-meshheading:16904708-Algorithms,
pubmed-meshheading:16904708-Animals,
pubmed-meshheading:16904708-Binding Sites,
pubmed-meshheading:16904708-DNA, Complementary,
pubmed-meshheading:16904708-Electrophysiology,
pubmed-meshheading:16904708-Humans,
pubmed-meshheading:16904708-KCNQ Potassium Channels,
pubmed-meshheading:16904708-KCNQ1 Potassium Channel,
pubmed-meshheading:16904708-KCNQ2 Potassium Channel,
pubmed-meshheading:16904708-Kinetics,
pubmed-meshheading:16904708-Morpholines,
pubmed-meshheading:16904708-Neurons,
pubmed-meshheading:16904708-Oocytes,
pubmed-meshheading:16904708-Patch-Clamp Techniques,
pubmed-meshheading:16904708-Point Mutation,
pubmed-meshheading:16904708-Tryptophan,
pubmed-meshheading:16904708-Xenopus laevis
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| pubmed:year |
2006
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| pubmed:articleTitle |
The acrylamide (S)-1 differentially affects Kv7 (KCNQ) potassium channels.
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| pubmed:affiliation |
The Danish National Research Foundation Centre for Cardiac Arrhythmia and Department of Medical Physiology, The Panum Institute, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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