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Received for publication November 8, 2005.
Revised January 18, 2006.
Accepted for publication January 18, 2006.
A genetic knock out 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 a ~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 TASK1/TASK3 heterodimers contribute(s) about one third of the current sensitive to TASK channel modulators in DLG TC neurons. The effects of the TASK channel blocker bupivacaine (20 µM), muscarine (50 µM), and H+ on ISO were reduced to about 60 %, 59 %, and shifted to more acidic pH values, respectively. The blocking effect of anandamide on ISO (30 µM; 23 ± 3 % current decrease in 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 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. Electroencephalographic 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 knock out of TASK-1 did not produce severe deficits in the thalamocortical system.
Key words:
Muscarinic cholinergic, Ion channel regulation, Local anesthetics, Gq/11 family, Knockout
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