title: Effects of divalent cations and spermine on the K+ channel TASK-3 and on the outward current in thalamic neurons.
abstract: The potassium channels TASK-1 and TASK-3 show high sequence homology but differ in their sensitivity to extracellular divalent cations. Heterologous expression in HEK293 cells showed that the single-channel conductance of TASK-3 increased approximately four-fold after removal of external divalent cations, whereas the conductance of TASK-1 was unaffected. Replacing the glutamate at position 70 of TASK-3 by a lysine or arginine residue abolished the sensitivity to divalent cations. The reverse mutation in TASK-1 (K70E) induced sensitivity to divalent cations. The organic polycations spermine and ruthenium red modulated the conductance of TASK-3 in a similar way as Ca2+ or Mg2+. Our data suggest that these effects were mediated by shielding of the negative charges in the extracellular loops of TASK-3. Whole-cell currents carried by TASK-3 channels were inhibited by spermine and ruthenium red even in the presence of external divalent cations. These data suggest that, in addition to their effect on single-channel conductance, spermine and ruthenium red decreased the open probability of TASK-3 channels, probably by binding to residue E70. The standing outward current in thalamocortical relay neurons, which is largely carried by TASK channels, was also inhibited by divalent cations and spermine. Using the differential sensitivity of TASK-1 and TASK-3 to divalent cations and spermine we found that about 20% of the standing outward current in thalamocortical relay neurons flows through TASK-3 channels. We conclude from our results that inhibition of TASK-3 channels may contribute to the neuromodulatory effect of spermine released from neurons during repetitive activity or during hypoxia.
authors.affiliation: Institut für Physiologie, Universität Marburg, Deutschhausstrasse 2, 35037 Marburg, Germany.
authors.forename: Boris
authors.initials: B
authors.lastname: Musset
authors.forename: Sven G
authors.initials: SG
authors.lastname: Meuth
authors.forename: Gong Xin
authors.initials: GX
authors.lastname: Liu
authors.forename: Christian
authors.initials: C
authors.lastname: Derst
authors.forename: Sven
authors.initials: S
authors.lastname: Wegner
authors.forename: Hans-Christian
authors.initials: HC
authors.lastname: Pape
authors.forename: Thomas
authors.initials: T
authors.lastname: Budde
authors.forename: Regina
authors.initials: R
authors.lastname: Preisig-Müller
authors.forename: Jürgen
authors.initials: J
authors.lastname: Daut
mesh_terms: D000818:Animals; D002118:Calcium / Q000008:administration & dosage*; D002412:Cations / Q000008:administration & dosage; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D008274:Magnesium / Q000008:administration & dosage*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D024683:Potassium Channels, Tandem Pore Domain / Q000378:metabolism*; D051381:Rats; D020318:Rats, Long-Evans; D013096:Spermine / Q000008:administration & dosage*; D013788:Thalamus / Q000187:drug effects / Q000502:physiology*
chemical_list: D002412:Cations; C407082:Kcnk9 protein, rat; D009419:Nerve Tissue Proteins; D024683:Potassium Channels, Tandem Pore Domain; C420132:potassium channel subfamily K member 3; D013096:Spermine; D008274:Magnesium; D002118:Calcium