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Discovery of a Novel Activator of KCNQ1-KCNE1 K+ Channel Complexes

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  • Karen Mruk
  • William R Kobertz

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.

Suggested Citation

  • Karen Mruk & William R Kobertz, 2009. "Discovery of a Novel Activator of KCNQ1-KCNE1 K+ Channel Complexes," PLOS ONE, Public Library of Science, vol. 4(1), pages 1-9, January.
    • Handle: RePEc:plo:pone00:0004236
    DOI: 10.1371/journal.pone.0004236
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    References listed on IDEAS

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    1. Björn C. Schroeder & Siegfried Waldegger & Susanne Fehr & Markus Bleich & Richard Warth & Rainer Greger & Thomas J. Jentsch, 2000. "A constitutively open potassium channel formed by KCNQ1 and KCNE3," Nature, Nature, vol. 403(6766), pages 196-199, January.
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    1. Girolamo Di Maio & Ines Villano & Ciro Rosario Ilardi & Antonietta Messina & Vincenzo Monda & Ashlei Clara Iodice & Chiara Porro & Maria Antonietta Panaro & Sergio Chieffi & Giovanni Messina & Marcell, 2023. "Mechanisms of Transmission and Processing of Pain: A Narrative Review," IJERPH, MDPI, vol. 20(4), pages 1-19, February.
    2. Katrien Willegems & Jodene Eldstrom & Efthimios Kyriakis & Fariba Ataei & Harutyun Sahakyan & Ying Dou & Sophia Russo & Filip Petegem & David Fedida, 2022. "Structural and electrophysiological basis for the modulation of KCNQ1 channel currents by ML277," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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