GSBS Student Publications
GSBS Program
Biochemistry & Molecular Pharmacology
UMMS Affiliation
Department of Biochemistry and Molecular Pharmacology
Date
1-21-2009
Document Type
Article
Medical Subject Headings
KCNQ1 Potassium Channel; Potassium Channels, Voltage-Gated; Boronic Acids
Disciplines
Biochemistry, Biophysics, and Structural Biology
Abstract
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.
Related Resources
Journal Title
PLoS ONE
PubMed ID
19156197
Repository Citation
Mruk, Karen and Kobertz, William R., "Discovery of a novel activator of KCNQ1-KCNE1 K channel complexes." (2009). GSBS Student Publications. 1589.
https://escholarship.umassmed.edu/gsbs_sp/1589
Comments
Citation: PLoS ONE. 2009;4(1):e4236. Epub 2009 Jan 21. Link to article on publisher's site
Copyright: © 2009 Mruk et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.