The Contribution of TWIK-Related Acid Sensitive K+ Containing Channels to the Function of Dorsal Lateral Geniculate Thalamocortical Relay Neurons

S. G. Meuth, M. I. Aller, T. Munsch, T. Schuhmacher, T. Seidenbecher, P. Meuth, C. Kleinschnitz, H. C. Pape, H. Wiendl, William Wisden, T. Budde

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    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 similar to 19% decrease in amplitude of the standing outward current (I-SO) and a 3 +/- 1-mV depolarizing shift in resting membrane potential (V rest) 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 mu M), of muscarine (50 mu M), and of H+ on I-SO were reduced to approximately 60%, 59%, and shifted to more acidic pH values, respectively. The blocking effect of anandamide on I SO [30 mu M; 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 anandamide derivative methanandamide (20 mu M; 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. Electro-corticograms and sleep/wake times were unchanged in TASK1(-/-) mice. In conclusion, our findings demonstrate a significant contribution of TASK-1 channels to I-SO in DLG TC neurons, although the genetic knockout of TASK-1 did not produce severe deficits in the thalamocortical system.

    Original languageEnglish
    Pages (from-to)1468-1476
    Number of pages8
    JournalMolecular Pharmacology
    Volume69
    DOIs
    Publication statusPublished - 2006

    Keywords

    • DOMAIN POTASSIUM CHANNEL
    • CEREBELLAR GRANULE NEURONS
    • 2 PORE DOMAINS
    • TASK CHANNELS
    • INHIBITION
    • TANDEM
    • CELLS
    • SUBUNITS
    • CONDUCTANCE
    • MOTONEURONS

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