| http://purl.uniprot.org/citations/23002961 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/23002961 | http://www.w3.org/2000/01/rdf-schema#comment | "The KCNQ2/3 channel has emerged as a drug target for a number of neurological disorders including pain and epilepsy. Known KCNQ2/3 openers have effects on two distinct biophysical properties of the channel: (1) a hyperpolarizing shift in the voltage dependence of channel activation (V(1/2)), and (2) an increase in channel open probability or peak whole-cell current. The current high-throughput screening assays for KCNQ2/3 openers measure changes of channel activity at sub-peak conductances and the output measure is a combination of effects on V(1/2) shift and peak current. Here, we describe a medium-throughput electrophysiological assay for screening KCNQ2/3 openers using the QPatch HT platform. We employed a double-pulse protocol that measures the shift in V(1/2) and the change in current amplitude at peak conductance voltage. Retigabine along with novel KCNQ2/3 openers were evaluated in this assay. Three classes of KCNQ2/3 openers were identified based on the hyperpolarizing shift in V(1/2) and the change in peak current. All three classes of compounds caused a hyperpolarizing shift in V(1/2), but they were differentiated by their respective effects on peak current amplitude (increase, decrease, or only modestly affecting peak current amplitude). KCNQ2/3 blockers were also identified with this assay. These compounds blocked currents without affecting voltage-dependent activation. In summary, we have developed a medium-throughput assay that can reliably detect changes in the biophysical properties of the KCNQ2/3 channel, V(1/2), and peak current amplitude, and therefore may serve as a reliable assay to evaluate KCNQ2/3 openers and blockers."xsd:string |
| http://purl.uniprot.org/citations/23002961 | http://purl.org/dc/terms/identifier | "doi:10.1089/adt.2012.446"xsd:string |
| http://purl.uniprot.org/citations/23002961 | http://purl.uniprot.org/core/author | "Zhang D."xsd:string |
| http://purl.uniprot.org/citations/23002961 | http://purl.uniprot.org/core/author | "Zhang X.F."xsd:string |
| http://purl.uniprot.org/citations/23002961 | http://purl.uniprot.org/core/author | "Yao B."xsd:string |
| http://purl.uniprot.org/citations/23002961 | http://purl.uniprot.org/core/author | "Surowy C.S."xsd:string |
| http://purl.uniprot.org/citations/23002961 | http://purl.uniprot.org/core/author | "Jarvis M.F."xsd:string |
| http://purl.uniprot.org/citations/23002961 | http://purl.uniprot.org/core/author | "Neelands T.R."xsd:string |
| http://purl.uniprot.org/citations/23002961 | http://purl.uniprot.org/core/author | "McGaraughty S."xsd:string |
| http://purl.uniprot.org/citations/23002961 | http://purl.uniprot.org/core/date | "2013"xsd:gYear |
| http://purl.uniprot.org/citations/23002961 | http://purl.uniprot.org/core/name | "Assay Drug Dev Technol"xsd:string |
| http://purl.uniprot.org/citations/23002961 | http://purl.uniprot.org/core/pages | "17-24"xsd:string |
| http://purl.uniprot.org/citations/23002961 | http://purl.uniprot.org/core/title | "Development and validation of a medium-throughput electrophysiological assay for KCNQ2/3 channel openers using QPatch HT."xsd:string |
| http://purl.uniprot.org/citations/23002961 | http://purl.uniprot.org/core/volume | "11"xsd:string |
| http://purl.uniprot.org/citations/23002961 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/23002961 |
| http://purl.uniprot.org/citations/23002961 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/23002961 |
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