Hydrogen bonds as molecular timers for slow inactivation in voltage-gated potassium channels

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

doi:10.7554/eLife.01289

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Hydrogen bonds as molecular timers for slow inactivation in voltage-gated potassium channels

Journal article

Open access

Peer reviewed

Hydrogen bonds as molecular timers for slow inactivation in voltage-gated potassium channels

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

eLife, Vol.2, pp.e01289-e01289

12/10/2013

DOI: 10.7554/eLife.01289

PMCID: PMC3852034

PMID: 24327560

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Abstract

Voltage-gated potassium (Kv) channels enable potassium efflux and membrane repolarization in excitable tissues. Many Kv channels undergo a progressive loss of ion conductance in the presence of a prolonged voltage stimulus, termed slow inactivation, but the atomic determinants that regulate the kinetics of this process remain obscure. Using a combination of synthetic amino acid analogs and concatenated channel subunits we establish two H-bonds near the extracellular surface of the channel that endow Kv channels with a mechanism to time the entry into slow inactivation: an intra-subunit H-bond between Asp447 and Trp434 and an inter-subunit H-bond connecting Tyr445 to Thr439. Breaking of either interaction triggers slow inactivation by means of a local disruption in the selectivity filter, while severing the Tyr445-Thr439 H-bond is likely to communicate this conformational change to the adjacent subunit(s). DOI: http://dx.doi.org/10.7554/eLife.01289.001.

Sequence Homology, Amino Acid

Amino Acid Sequence

Hydrogen Bonding

Potassium Channels - physiology

Molecular Sequence Data

Potassium Channels - chemistry

Ion Channel Gating

Details

Title: Subtitle: Hydrogen bonds as molecular timers for slow inactivation in voltage-gated potassium channels
Creators: Stephan A Pless - Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, Canada
Jason D Galpin
Ana P Niciforovic
Harley T Kurata
Christopher A Ahern
Resource Type: Journal article
Publication Details: eLife, Vol.2, pp.e01289-e01289
DOI: 10.7554/eLife.01289
PMID: 24327560
PMCID: PMC3852034
NLM abbreviation: Elife
ISSN: 2050-084X
eISSN: 2050-084X
Publisher: England
Grant note: GM106569 / NIGMS NIH HHS MOP-56858 / Canadian Institutes of Health Research R01 GM106569 / NIGMS NIH HHS
Language: English
Date published: 12/10/2013
Academic Unit: Molecular Physiology and Biophysics; Iowa Neuroscience Institute
Record Identifier: 9984065394702771

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