IMSS Seminar

IMSS Seminar 15-07

Start:2015/09/11 (Fri) 1:30 PM
End:2015/09/11 (Fri) 2:30 PM
Location:Rinko-shitu 1 on the 3rd floor of 4-go-kan

Speaker:Crina Nimigean (Associate Prof.), Cornell University
Lecture:Molecular Gate Locations in Potassium Channels


Ion channel opening and closing is fundamental to cellular signaling and homeostasis. Gates that control K+ channel activity were found both at an intracellular pore constriction and within the selectivity filter near the extracellular side but the specific location of the gate that opens Ca2+-activated K+ channels has remained elusive. Using the Methanobacterium thermoautotrophicum homolog (MthK) and both single-channel recording in lipid bilayers and a stopped-flow fluorometric assay for fast channel activation, we show that intracellular quaternary ammonium blockers bind to closed MthK channels. Since the blockers are known to bind inside a central channel cavity, past the intracellular entryway, the gate must be within the selectivity filter. Furthermore, the blockers access the closed channel slower than the open channel, suggesting that the intracellular entryway narrows upon pore closure, without preventing access of either the blockers or the smaller K+. Thus, voltage- and Ca2+-dependent gating in MthK occur at the selectivity filter, with coupled movement of the intracellular helices.

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