RT Journal Article SR Electronic T1 The Contribution of TWIK-Related Acid-Sensitive K+-Containing Channels to the Function of Dorsal Lateral Geniculate Thalamocortical Relay Neurons JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 1468 OP 1476 DO 10.1124/mol.105.020594 VO 69 IS 4 A1 Sven G. Meuth A1 M. Isabel Aller A1 Thomas Munsch A1 Thekla Schuhmacher A1 Thomas Seidenbecher A1 Patrick Meuth A1 Christoph Kleinschnitz A1 Hans-Christian Pape A1 Heinz Wiendl A1 William Wisden A1 Thomas Budde YR 2006 UL http://molpharm.aspetjournals.org/content/69/4/1468.abstract AB 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 ∼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 μM), of muscarine (50 μM), 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 μM; 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 μM; 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.