Zinc pyrithione-mediated activation of voltage-gated KCNQ potassium channels rescues epileptogenic mutants.

Zinc pyrithione-mediated activation of voltage-gated KCNQ potassium channels rescues epileptogenic mutants. Research Abstract Details 

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Zinc pyrithione-mediated activation of voltage-gated KCNQ potassium channels rescues epileptogenic mutants. Abstract Text:

Qiaojie Xiong,Haiyan Sun,Min Li,

KCNQ potassium channels are activated by changes in transmembrane voltage and play an important role in controlling electrical excitability. Human mutations of KCNQ2 and KCNQ3 potassium channel genes result in reduction or loss of channel activity and cause benign familial neonatal convulsions (BFNCs). Thus, small molecules capable of augmenting KCNQ currents are essential both for understanding the mechanism of channel activity and for developing therapeutics. We performed a high-throughput screen in search for agonistic compounds potentiating KCNQ potassium channels. Here we report identification of a new opener, zinc pyrithione (1), which activates both recombinant and native KCNQ M currents. Interactions with the channel protein cause an increase of single-channel open probability that could fully account for the overall conductance increase. Separate point mutations have been identified that either shift the concentration dependence or affect potentiation efficacy, thereby providing evidence for residues influencing ligand binding and downstream events. Furthermore, zinc pyrithione is capable of rescuing the mutant channels causal to BFNCs.

Zinc pyrithione-mediated activation of voltage-gated KCNQ potassium channels rescues epileptogenic mutants. Publishing Authors By Initials

Q Xiong,H Sun,M Li,

For similar investigative techniques: epidemiologic methods: statistics as topic: sensitivity and specificity research abstracts see: investigative techniques: epidemiologic methods: statistics as topic: sensitivity and specificity research

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Zinc pyrithione-mediated activation of voltage-gated KCNQ potassium channels rescues epileptogenic mutants. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Nature chemical biology

VOLUME: 3

Page Numbers: 287-96

Journal Abbreviation:

ISSN: 1552-4450

DAY: 15

MONTH: 04

YEAR: 2007

Zinc pyrithione-mediated activation of voltage-gated KCNQ potassium channels rescues epileptogenic mutants. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 101231976

Zinc pyrithione-mediated activation of voltage-gated KCNQ potassium channels rescues epileptogenic mutants. Keywords Mesh Terms:

KEYWORDS: Sensitivity and Specificity

MESH TERMS: pharmacology

Chemical & Substance for Abstract: Zinc pyrithione-mediated activation of voltage-gated KCNQ potassium channels rescues epileptogenic mutants. Information

Substance Name: zinc pyrithione

Registry Number: 13463-41-7

Grant and Affiliation Information for Zinc pyrithione-mediated activation of voltage-gated KCNQ potassium channels rescues epileptogenic mutants.

AFFILIATION: Department of Neuroscience, High Throughput Biology Center, School of Medicine, Johns Hopkins University, 733 North Broadway, Baltimore, Maryland 21205, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: GM70959

ACRONYM: GM

MEDLINETA: Nat Chem Biol

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