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dc.contributor.authorMruk, Karen
dc.contributor.authorKobertz, William R.
dc.date2022-08-11T08:08:52.000
dc.date.accessioned2022-08-23T16:10:53Z
dc.date.available2022-08-23T16:10:53Z
dc.date.issued2009-01-21
dc.date.submitted2009-04-01
dc.identifier.citation<p>PLoS ONE. 2009;4(1):e4236. Epub 2009 Jan 21. <a href="http://dx.doi.org/10.1371/journal.pone.0004236" target="_blank">Link to article on publisher's site</a></p>
dc.identifier.issn1932-6203
dc.identifier.doi10.1371/journal.pone.0004236
dc.identifier.pmid19156197
dc.identifier.urihttp://hdl.handle.net/20.500.14038/33039
dc.description.abstractKCNQ1 voltage-gated K(+) channels (Kv7.1) associate with the family of five KCNE peptides to form complexes with diverse gating properties and pharmacological sensitivities. The varied gating properties of the different KCNQ1-KCNE complexes enables the same K(+) channel to function in both excitable and non excitable tissues. Small molecule activators would be valuable tools for dissecting the gating mechanisms of KCNQ1-KCNE complexes; however, there are very few known activators of KCNQ1 channels and most are ineffective on the physiologically relevant KCNQ1-KCNE complexes. Here we show that a simple boronic acid, phenylboronic acid (PBA), activates KCNQ1/KCNE1 complexes co-expressed in Xenopus oocytes at millimolar concentrations. PBA shifts the voltage sensitivity of KCNQ1 channel complexes to favor the open state at negative potentials. Analysis of different-sized charge carriers revealed that PBA also targets the permeation pathway of KCNQ1 channels. Activation by the boronic acid moiety has some specificity for the Kv7 family members (KCNQ1, KCNQ2/3, and KCNQ4) since PBA does not activate Shaker or hERG channels. Furthermore, the commercial availability of numerous PBA derivatives provides a large class of compounds to investigate the gating mechanisms of KCNQ1-KCNE complexes.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=19156197&dopt=Abstract">Link to article in PubMed</a>
dc.relation.urlhttp://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0004236
dc.subjectKCNQ1 Potassium Channel; Potassium Channels, Voltage-Gated; Boronic Acids
dc.subjectBiochemistry, Biophysics, and Structural Biology
dc.titleDiscovery of a novel activator of KCNQ1-KCNE1 K channel complexes.
dc.typeJournal Article
dc.source.journaltitlePLoS ONE
dc.source.volume4
dc.source.issue1
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=2588&amp;context=gsbs_sp&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_sp/1589
dc.identifier.contextkey807880
refterms.dateFOA2022-08-23T16:10:53Z
html.description.abstract<p>KCNQ1 voltage-gated K(+) channels (Kv7.1) associate with the family of five KCNE peptides to form complexes with diverse gating properties and pharmacological sensitivities. The varied gating properties of the different KCNQ1-KCNE complexes enables the same K(+) channel to function in both excitable and non excitable tissues. Small molecule activators would be valuable tools for dissecting the gating mechanisms of KCNQ1-KCNE complexes; however, there are very few known activators of KCNQ1 channels and most are ineffective on the physiologically relevant KCNQ1-KCNE complexes. Here we show that a simple boronic acid, phenylboronic acid (PBA), activates KCNQ1/KCNE1 complexes co-expressed in Xenopus oocytes at millimolar concentrations. PBA shifts the voltage sensitivity of KCNQ1 channel complexes to favor the open state at negative potentials. Analysis of different-sized charge carriers revealed that PBA also targets the permeation pathway of KCNQ1 channels. Activation by the boronic acid moiety has some specificity for the Kv7 family members (KCNQ1, KCNQ2/3, and KCNQ4) since PBA does not activate Shaker or hERG channels. Furthermore, the commercial availability of numerous PBA derivatives provides a large class of compounds to investigate the gating mechanisms of KCNQ1-KCNE complexes.</p>
dc.identifier.submissionpathgsbs_sp/1589
dc.contributor.departmentDepartment of Biochemistry and Molecular Pharmacology
dc.source.pagese4236
dc.contributor.studentKaren Mruk


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