TY - JOUR TI - Hydrogen bonds as molecular timers for slow inactivation in voltage-gated potassium channels AU - Pless, Stephan A AU - Galpin, Jason D AU - Niciforovic, Ana P AU - Kurata, Harley T AU - Ahern, Christopher A A2 - Aldrich, Richard VL - 2 PY - 2013 DA - 2013/12/10 SP - e01289 C1 - eLife 2013;2:e01289 DO - 10.7554/eLife.01289 UR - https://doi.org/10.7554/eLife.01289 AB - 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). KW - neuroscience KW - ion channel gating KW - unnatural amino acid KW - hydrogen bond KW - channel inactivation KW - molecular timer JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -