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 ϩ (TASK)-1 channels to the function of dorsal lateral geniculate nucleus (DLG) thalamocortical relay (TC) neurons. Disruption of TASK-1 function produced an ϳ19% decrease in amplitude of the standing outward current (I SO ) and a 3 Ϯ 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 M), of muscarine (50 M), and of H ϩ 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 M; 23 Ϯ 3% current decrease in wild type (WT)] was absent in TASK-1 knockout (TASK-1 Ϫ/Ϫ ) mice (9 Ϯ 6% current increase). Comparable results were obtained with the more stable anandamide derivative methanandamide (20 M; 20 Ϯ 2% decrease in WT; 4 Ϯ 6% increase in TASK-1 Ϫ/Ϫ ). 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 Ϫ/Ϫ 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.

TASK-3 Two-Pore Domain Potassium Channels Enable Sustained High-Frequency Firing in Cerebellar Granule Neurons

“…In the current study, we examined the consequence of genetically removing TASK-3 expression on the excitability of adult CGNs. In contrast to the situation for TASK-1 knock-out (KO) neurons (Aller et al, 2005;Meuth et al, 2006), a significant depolarization of the RMP was observed in CGNs lacking TASK-3. In addition, a clear increase in the degree of AP accommodation was apparent both at threshold and suprathreshold levels of depolarization.…”

“…The increased input conductance associated with K 2P channel opening will further reduce excitability by attenuating excitatory drive (Goldstein et al, 2001;Patel and Honoré, 2001). Many neuromodulators promote closure of K 2P channels (Talley et al, 2000;Chemin et al, 2003;Heurteaux et al, 2006;Meuth et al, 2006;Mathie, 2007), and the conventional view would be that K 2P closure would increase neuronal excitability.…”

TASK Channels Determine pH Sensitivity in Select Respiratory Neurons But Do Not Contribute to Central Respiratory Chemosensitivity

“…In addition, it has been proposed that TASK channels may be involved in regulation of respiration by peripheral chemoreceptors (e.g., via hypoxic inhibition of TASK-like channels in carotid body glomus cells) (Buckler, 2007). In light of this, it is perhaps surprising that TASK knock-out mice, including the double TASK Ϫ/Ϫ mice reported here for the first time, present such an unremarkable respiratory and neurological phenotype (Aller et al, 2005;Linden et al, 2006;Meuth et al, 2006;Brickley et al, 2007). Indeed, we also tested peripheral chemosensory responses of these mice and found a significant hyperventilation in TASK Ϫ/Ϫ double knock-out mice exposed to 10% O 2 (n ϭ 5, p Ͻ 0.0005 by two-way RM-ANOVA) that was not different from that in control mice (n ϭ 6, p ϭ 0.64).…”

“…Expression of TASK channel transcripts is widespread throughout the CNS (Karschin et al, 2001;Talley et al, 2001;Vega-Saenz et al, 2001), and it is now clear that TASK-like background K ϩ currents contribute to regulation of excitability in numerous cell types (Millar et al, 2000;Sirois et al, 2000;Han et al, 2003;Meuth et al, 2003Meuth et al, , 2006Berg et al, 2004;Aller et al, 2005;Taverna et al, 2005;Burdakov et al, 2006;Torborg et al, 2006;Brickley et al, 2007), including many central respiratory-related neurons Washburn et al, 2002Washburn et al, , 2003. In addition, it has been proposed that TASK channels may be involved in regulation of respiration by peripheral chemoreceptors (e.g., via hypoxic inhibition of TASK-like channels in carotid body glomus cells) (Buckler, 2007).…”

Striatal Cholinergic Interneurons Express a Receptor-Insensitive Homomeric TASK-3–Like Background K+ Current

“…We could attribute this background K ϩ current to homomeric TASK-3 channels because: 1) it was strongly inhibited by acidification but unaffected by alkalization (from pH 7.3), as expected for TASK-3 but not other TASK channels; and 2) it was potently inhibited by Zn 2ϩ at concentrations selective among TASK channels for TASK-3 homomers. These cholinergic striatal interneurons are thus distinct from other neurons studied to date, where TASK-like currents appear to represent an admixture of homomeric TASK-1 and TASK-3 as well as heteromeric TASK-1/TASK-3 channels (Berg et al 2004;Kang et al 2003;Meuth et al 2006).…”