GSBS Student Publications

Student Author(s)

Karen Mruk

GSBS Program

Biochemistry & Molecular Pharmacology

Publication Date

2009-01-21

UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology

Document Type

Article

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.

DOI of Published Version

10.1371/journal.pone.0004236

Source

PLoS ONE. 2009;4(1):e4236. Epub 2009 Jan 21. Link to article on publisher's site

Journal/Book/Conference Title

PLoS ONE

Related Resources

Link to article in PubMed

PubMed ID

19156197

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