title: Dilated and defunct K channels in the absence of K+.
abstract: Potassium ions are vital for maintaining functionality of K channels. In their absence, many K channel types enter a long-lasting defunct condition characterized by absence of conductance and drastic changes in gating current. We show that channels pass through a dilated condition with altered selectivity as they are becoming defunct. To characterize these abnormalities we examined gating and ionic currents generated by Shaker IR and by three nonconducting mutants, W434F, D447N, and Y445A, in 0 K+. On entering the dilated condition, Shaker IR becomes permeable to Na+ and tetramethylammonium-positive (TMA+), signaling deformation of the selectivity filter. When dilated, nearly normal closing is possible at -140 mV. At -80 mV, however, closing is very slow and channels stray from the dilated into the defunct condition. Restoration from defunct to dilated condition requires tens of seconds at 0 mV and can occur in the absence of K+. W434F and D447N are similar to Shaker IR, showing Na+ and TMA+ permeability when dilated. The defunct gating currents are similar in Shaker IR and these two mutants and are reminiscent of the early transitions of normal gating. Y445A does not become defunct and shows Na+ but not TMA+ permeability on K+ removal.
authors.affiliation: Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
authors.forename: A
authors.initials: A
authors.lastname: Loboda
authors.forename: A
authors.initials: A
authors.lastname: Melishchuk
authors.forename: C
authors.initials: C
authors.lastname: Armstrong
mesh_terms: D019943:Amino Acid Substitution; D002460:Cell Line; D004553:Electric Conductivity; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects*; D007700:Kinetics; D017354:Point Mutation; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology*; D015221:Potassium Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011487:Protein Conformation; D051637:Shaker Superfamily of Potassium Channels
chemical_list: D015221:Potassium Channels; D051637:Shaker Superfamily of Potassium Channels; D011188:Potassium