title: Hysteresis of KcsA potassium channel's activation- deactivation gating is caused by structural changes at the channel's selectivity filter.
abstract: Mode-shift or hysteresis has been reported in ion channels. Voltage-shift for gating currents is well documented for voltage-gated cation channels (VGCC), and it is considered a voltage-sensing domain's (VSD) intrinsic property. However, uncoupling theShakerK+channel's pore domain (PD) from the VSD prevented the mode-shift of the gating currents. Consequently, it was proposed that an open-state stabilization of the PD imposes a mechanical load on the VSD, which causes its mode-shift. Furthermore, the mode-shift displayed by hyperpolarization-gated cation channels is likely caused by structural changes at the channel's PD similar to those underlying C-type inactivation. To demonstrate that the PD of VGCC undergoes hysteresis, it is imperative to study its gating process in the absence of the VSD. A back-door strategy is to use KcsA (a K+channel from the bacteriaStreptomyces lividans) as a surrogate because it lacks a VSD and exhibits an activation coupled to C-type inactivation. By directly measuring KcsA's activation gate opening and closing in conditions that promote or halt C-type inactivation, we have found (i) that KcsA undergoes mode-shift of gating when having K+as the permeant ion; (ii) that Cs+or Rb+, known to halt C-inactivation, prevented mode-shift of gating; and (iii) that, in the total absence of C-type inactivation, KcsA's mode-shift was prevented. Finally, our results demonstrate that an allosteric communication causes KcsA's activation gate to "remember" the conformation of the selectivity filter, and hence KcsA requires a different amount of energy for opening than for closing.
authors.affiliation: Department of Cell Physiology and Molecular Biophysics and Center for Membrane Protein Research, Texas Tech University Health Sciences Center, Lubbock, TX 79430.
authors.forename: Cholpon
authors.initials: C
authors.lastname: Tilegenova
authors.affiliation: Department of Cell Physiology and Molecular Biophysics and Center for Membrane Protein Research, Texas Tech University Health Sciences Center, Lubbock, TX 79430.
authors.forename: D Marien
authors.initials: DM
authors.lastname: Cortes
authors.affiliation: Department of Cell Physiology and Molecular Biophysics and Center for Membrane Protein Research, Texas Tech University Health Sciences Center, Lubbock, TX 79430 luis.cuello@ttuhsc.edu.
authors.forename: Luis G
authors.initials: LG
authors.lastname: Cuello
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002586:Cesium / Q000737:chemistry; D020450:Heavy Ions; D015640:Ion Channel Gating; D007700:Kinetics; D008564:Membrane Potentials; D008958:Models, Molecular; D009154:Mutation; D015221:Potassium Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011487:Protein Conformation; D012413:Rubidium / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D001426:Bacterial Proteins; D015221:Potassium Channels; C107790:prokaryotic potassium channel; D002586:Cesium; D012413:Rubidium
keywords: C-type inactivation; KcsA; hysteresis; mode-shift; potassium channels