Discovery of a novel activator of KCNQ1-KCNE1 K channel complexes.
Student AuthorsKaren Mruk
UMass Chan AffiliationsDepartment of Biochemistry and Molecular Pharmacology
KeywordsKCNQ1 Potassium Channel; Potassium Channels, Voltage-Gated; Boronic Acids
Biochemistry, Biophysics, and Structural Biology
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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.
PLoS ONE. 2009;4(1):e4236. Epub 2009 Jan 21. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/33039
Related ResourcesLink to article in PubMed