title: Calcium ions open a selectivity filter gate during activation of the MthK potassium channel.
abstract: Ion channel opening and closing are fundamental to cellular signalling 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 Ca(2+)-activated K(+) channels has remained elusive. Using the Methanobacterium thermoautotrophicum homologue (MthK) 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, Ca(2+)-dependent gating in MthK occurs at the selectivity filter with coupled movement of the intracellular helices.
authors.affiliation: Department of Anesthesiology, Weill Cornell Medical College, 1300 York Avenue, New York, New York 10021, USA.|Department of Physiology and Biophysics, Weill Cornell Medical College, 1300 York Avenue, New York, New York 10021, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Posson
authors.affiliation: Department of Anesthesiology, Weill Cornell Medical College, 1300 York Avenue, New York, New York 10021, USA.|Department of Physiology and Biophysics, Weill Cornell Medical College, 1300 York Avenue, New York, New York 10021, USA.
authors.forename: Radda
authors.initials: R
authors.lastname: Rusinova
authors.affiliation: Department of Physiology and Biophysics, Weill Cornell Medical College, 1300 York Avenue, New York, New York 10021, USA.
authors.forename: Olaf S
authors.initials: OS
authors.lastname: Andersen
authors.affiliation: Department of Anesthesiology, Weill Cornell Medical College, 1300 York Avenue, New York, New York 10021, USA.|Department of Physiology and Biophysics, Weill Cornell Medical College, 1300 York Avenue, New York, New York 10021, USA.|Department of Biochemistry, Weill Cornell Medical College, 1300 York Avenue, New York, New York 10021, USA.
authors.forename: Crina M
authors.initials: CM
authors.lastname: Nimigean
mesh_terms: D002118:Calcium / Q000378:metabolism*; D007700:Kinetics; D017014:Methanobacterium / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism*; D000644:Quaternary Ammonium Compounds
chemical_list: D015221:Potassium Channels; D000644:Quaternary Ammonium Compounds; C027435:tetrapentylammonium; D002118:Calcium