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

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 kine...

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Bibliographic Details
Published in:eLife
Main Authors: Stephan A Pless, Jason D Galpin, Ana P Niciforovic, Harley T Kurata, Christopher A Ahern
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2013-12-01
Subjects:
neuroscience
ion channel gating
unnatural amino acid
hydrogen bond
channel inactivation
molecular timer
Online Access:https://elifesciences.org/articles/01289
Description
Summary: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).
ISSN:2050-084X

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