Mutation of a single residue promotes gating of vertebrate and invertebrate two-pore domain potassium channels

Ismail Soussia, Sonia El Mouridi, Dawon Kang, Alice Leclercq-Blondel, Lamyaa Khoubza, Philippe Tardy, Nora Zariohi, Marie Gendrel, Florian Lesage, Eun-Jin Kim, Delphine Bichet, Olga Andrini () and Thomas Boulin ()
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Ismail Soussia: Université Claude Bernard Lyon 1
Sonia El Mouridi: Université Claude Bernard Lyon 1
Dawon Kang: Gyeongsang National University
Alice Leclercq-Blondel: Université Claude Bernard Lyon 1
Lamyaa Khoubza: Université de Nice Sophia Antipolis
Philippe Tardy: Université Claude Bernard Lyon 1
Nora Zariohi: Université Claude Bernard Lyon 1
Marie Gendrel: Université Claude Bernard Lyon 1
Florian Lesage: Université de Nice Sophia Antipolis
Eun-Jin Kim: Gyeongsang National University
Delphine Bichet: Université de Nice Sophia Antipolis
Olga Andrini: Université Claude Bernard Lyon 1
Thomas Boulin: Université Claude Bernard Lyon 1

Nature Communications, 2019, vol. 10, issue 1, 1-13

Abstract: Abstract Mutations that modulate the activity of ion channels are essential tools to understand the biophysical determinants that control their gating. Here, we reveal the conserved role played by a single amino acid position (TM2.6) located in the second transmembrane domain of two-pore domain potassium (K2P) channels. Mutations of TM2.6 to aspartate or asparagine increase channel activity for all vertebrate K2P channels. Using two-electrode voltage-clamp and single-channel recording techniques, we find that mutation of TM2.6 promotes channel gating via the selectivity filter gate and increases single channel open probability. Furthermore, channel gating can be progressively tuned by using different amino acid substitutions. Finally, we show that the role of TM2.6 was conserved during evolution by rationally designing gain-of-function mutations in four Caenorhabditis elegans K2P channels using CRISPR/Cas9 gene editing. This study thus describes a simple and powerful strategy to systematically manipulate the activity of an entire family of potassium channels.

Date: 2019
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-08710-3

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DOI: 10.1038/s41467-019-08710-3

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