Hydrogen bonds as molecular timers for slow inactivation in voltage-gated potassium channels
By Stephan A Pless, Jason D Galpin, Ana P Niciforovic, Harley T Kurata, and Christopher A Ahern.
Published in Elife 2013 Dec 10;2:e01289.
PMID: 24327560. PMCID: PMC3852034. Link to Pubmed page.
Core Facility: Membrane Protein Expression/Purification.
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).