The contribution of TWIK-related acid-sensitive K+-containing channels to the function of dorsal lateral geniculate thalamocortical relay neurons.
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.
Meuth
Sven G
SG
Institut für Experimentelle Epilepsieforschung, Westfälische Wilhelms-Universität Münster, Hüfferstr. 68, D-48149 Münster, Germany.
Aller
M Isabel
MI
Munsch
Thomas
T
Schuhmacher
Thekla
T
Seidenbecher
Thomas
T
Meuth
Patrick
P
Kleinschnitz
Christoph
C
Pape
Hans-Christian
HC
Wiendl
Heinz
H
Wisden
William
W
Budde
Thomas
T
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*
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