Contributions of counter-charge in a potassium channel voltage-sensor domain

Stephan A Pless; Jason D Galpin; Ana P Niciforovic; Christopher A Ahern

doi:10.1038/nchembio.622

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Contributions of counter-charge in a potassium channel voltage-sensor domain

Journal article

Peer reviewed

Contributions of counter-charge in a potassium channel voltage-sensor domain

Stephan A Pless, Jason D Galpin, Ana P Niciforovic and Christopher A Ahern

Nature chemical biology, Vol.7(9), pp.617-623

07/24/2011

DOI: 10.1038/nchembio.622

PMCID: PMC4933587

PMID: 21785425

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Abstract

Voltage-sensor domains couple membrane potential to conformational changes in voltage-gated ion channels and phosphatases. Highly coevolved acidic and aromatic side chains assist the transfer of cationic side chains across the transmembrane electric field during voltage sensing. We investigated the functional contribution of negative electrostatic potentials from these residues to channel gating and voltage sensing with unnatural amino acid mutagenesis, electrophysiology, voltage-clamp fluorometry and ab initio calculations. The data show that neutralization of two conserved acidic side chains in transmembrane segments S2 and S3, namely Glu293 and Asp316 in Shaker potassium channels, has little functional effect on conductance-voltage relationships, although Glu293 appears to catalyze S4 movement. Our results suggest that neither Glu293 nor Asp316 engages in electrostatic state-dependent charge-charge interactions with S4, likely because they occupy, and possibly help create, a water-filled vestibule.

Xenopus

Amino Acid Sequence

Potassium Channels, Voltage-Gated - chemistry

Glutamic Acid - genetics

Molecular Sequence Data

Static Electricity

Aspartic Acid - genetics

Ion Channel Gating - physiology

Animals

Membrane Potentials

Aspartic Acid - chemistry

Glutamic Acid - chemistry

Potassium Channels, Voltage-Gated - genetics

Details

Title: Subtitle: Contributions of counter-charge in a potassium channel voltage-sensor domain
Creators: Stephan A Pless - Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada
Jason D Galpin
Ana P Niciforovic
Christopher A Ahern
Resource Type: Journal article
Publication Details: Nature chemical biology, Vol.7(9), pp.617-623
DOI: 10.1038/nchembio.622
PMID: 21785425
PMCID: PMC4933587
NLM abbreviation: Nat Chem Biol
ISSN: 1552-4450
eISSN: 1552-4469
Publisher: Springer Science and Business Media LLC; United States
Grant note: 56858 / Canadian Institutes of Health Research 56858-1 / Canadian Institutes of Health Research
Language: English
Date published: 07/24/2011
Academic Unit: Molecular Physiology and Biophysics; Iowa Neuroscience Institute
Record Identifier: 9984070405702771

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