title: The contribution of TWIK-related acid-sensitive K+-containing channels to the function of dorsal lateral geniculate thalamocortical relay neurons.
abstract: A genetic knockout was used to determine the specific contribution of TWIK-related acid-sensitive K+ (TASK)-1 channels to the function of dorsal lateral geniculate nucleus (DLG) thalamocortical relay (TC) neurons. Disruption of TASK-1 function produced an approximately 19% decrease in amplitude of the standing outward current (ISO) and a 3 +/- 1-mV depolarizing shift in resting membrane potential (Vrest) of DLG neurons. We estimated that current through TASK-1 homodimers or TASK-1/TASK-3 heterodimers contribute(s) approximately one third of the current sensitive to TASK channel modulators in DLG TC neurons. The effects of the TASK channel blocker bupivacaine (20 microM), of muscarine (50 microM), and of H+ on ISO were reduced to approximately 60%, 59%, and shifted to more acidic pH values, respectively. The blocking effect of anandamide on ISO [30 microM; 23 +/- 3% current decrease in wild type (WT)] was absent in TASK-1 knockout (TASK-1-/-) mice (9 +/- 6% current increase). Comparable results were obtained with the more stable anand-amide derivative methanandamide (20 microM; 20 +/- 2% decrease in WT; 4 +/- 6% increase in TASK-1-/-). Current-clamp recordings revealed a muscarine-induced shift in TC neuron activity from burst to tonic firing in both mouse genotypes. Electrocorticograms and sleep/wake times were unchanged in TASK-1-/- mice. In conclusion, our findings demonstrate a significant contribution of TASK-1 channels to ISO in DLG TC neurons, although the genetic knockout of TASK-1 did not produce severe deficits in the thalamocortical system.
authors.affiliation: Institut für Experimentelle Epilepsieforschung, Westfälische Wilhelms-Universität Münster, Hüfferstr. 68, D-48149 Münster, Germany.
authors.forename: Sven G
authors.initials: SG
authors.lastname: Meuth
authors.forename: M Isabel
authors.initials: MI
authors.lastname: Aller
authors.forename: Thomas
authors.initials: T
authors.lastname: Munsch
authors.forename: Thekla
authors.initials: T
authors.lastname: Schuhmacher
authors.forename: Thomas
authors.initials: T
authors.lastname: Seidenbecher
authors.forename: Patrick
authors.initials: P
authors.lastname: Meuth
authors.forename: Christoph
authors.initials: C
authors.lastname: Kleinschnitz
authors.forename: Hans-Christian
authors.initials: HC
authors.lastname: Pape
authors.forename: Heinz
authors.initials: H
authors.lastname: Wiendl
authors.forename: William
authors.initials: W
authors.lastname: Wisden
authors.forename: Thomas
authors.initials: T
authors.lastname: Budde
mesh_terms: D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D001522:Behavior, Animal; D048588:Benzoxazines; D002045:Bupivacaine / Q000494:pharmacology; D004569:Electroencephalography; D063388:Endocannabinoids; D005829:Geniculate Bodies / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D017403:In Situ Hybridization; D008297:Male; D008564:Membrane Potentials; D051379:Mice; D018345:Mice, Knockout; D009025:Morpholines / Q000494:pharmacology; D009116:Muscarine / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D053284:Polyunsaturated Alkamides; D024683:Potassium Channels, Tandem Pore Domain / Q000235:genetics / Q000502:physiology*
chemical_list: D000779:Anesthetics, Local; D001095:Arachidonic Acids; D048588:Benzoxazines; D063388:Endocannabinoids; D009025:Morpholines; D009281:Naphthalenes; D009419:Nerve Tissue Proteins; D053284:Polyunsaturated Alkamides; D024683:Potassium Channels, Tandem Pore Domain; C420132:potassium channel subfamily K member 3; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D009116:Muscarine; C078814:anandamide; D002045:Bupivacaine