title: The voltage-dependent gate in MthK potassium channels is located at the selectivity filter.
abstract: Understanding how ion channels open and close their pores is crucial for comprehending their physiological roles. We used intracellular quaternary ammonium blockers, electrophysiology and X-ray crystallography to locate the voltage-dependent gate in MthK potassium channels from Methanobacterium thermoautotrophicum. Blockers bind in an aqueous cavity between two putative gates: an intracellular gate and the selectivity filter. Thus, these blockers directly probe gate location--an intracellular gate will prevent binding when closed, whereas a selectivity filter gate will always allow binding. Kinetic analysis of tetrabutylammonium block of single MthK channels combined with X-ray crystallographic analysis of the pore with tetrabutyl antimony unequivocally determined that the voltage-dependent gate, like the C-type inactivation gate in eukaryotic channels, is located at the selectivity filter. State-dependent binding kinetics suggest that MthK inactivation leads to conformational changes within the cavity and intracellular pore entrance.
authors.affiliation: Department of Anesthesiology, Weill Cornell Medical College, New York, New York, USA. djp2003@med.cornell.edu
authors.forename: David J
authors.initials: DJ
authors.lastname: Posson
authors.forename: Jason G
authors.initials: JG
authors.lastname: McCoy
authors.forename: Crina M
authors.initials: CM
authors.lastname: Nimigean
mesh_terms: D018360:Crystallography, X-Ray; D015640:Ion Channel Gating / Q000502:physiology*; D007700:Kinetics; D017014:Methanobacterium / Q000378:metabolism*; D008958:Models, Molecular; D024642:Potassium Channels, Voltage-Gated / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation; D000644:Quaternary Ammonium Compounds
chemical_list: D024642:Potassium Channels, Voltage-Gated; D000644:Quaternary Ammonium Compounds; C009405:tetrabutylammonium