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

Elife. 2013 Dec 10;2:e01289. doi: 10.7554/eLife.01289.

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.

Keywords: channel inactivation; hydrogen bonds; ion channel gating; molecular timers; neuroscience; unnatural amino acids.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Hydrogen Bonding*
  • Ion Channel Gating*
  • Molecular Sequence Data
  • Potassium Channels / chemistry
  • Potassium Channels / physiology*
  • Sequence Homology, Amino Acid

Substances

  • Potassium Channels