title: Contribution of TWIK-related acid-sensitive K+ channel 1 (TASK1) and TASK3 channels to the control of activity modes in thalamocortical neurons.
abstract: The thalamocortical network is characterized by rhythmic burst activity during natural sleep and tonic single-spike activity during wakefulness. The change between these two activity modes is partially governed by transmitters acting on leak K+ currents in the thalamus, although the nature of the constituting ion channels is not yet known. In the present study, the contribution of members of the two-pore domain K+ channel family to the leak current was investigated using whole-cell patch-clamp techniques and molecular biological techniques. RT-PCR and in situ hybridization revealed the expression of TWIK-related acid-sensitive K+ channel 1 (TASK 1) and TASK3 channels in the rat dLGN. Voltage-clamp recordings of thalamocortical relay neurons in slice preparations demonstrated the existence of a current component sensitive to the TASK channel blocker bupivacaine, which reversed at the presumed K+ equilibrium potential, showed outward rectification, and contributed approximately 40% to the standing outward current at depolarized values of the membrane potential (-28 mV). The pharmacological profile was indicative of TASK channels, in that the current was sensitive to changes in extracellular pH, reduced by muscarine and increased by halothane, and these effects were occluded by a near-maximal action of bupivacaine. Pharmacological manipulation of this current under current-clamp conditions resulted in a shift between burst and tonic firing modes. It is concluded that TASK1 and TASK3 channels contribute to the muscarine- and halothane-sensitive conductance in thalamocortical relay neurons, thereby contributing to the change in the activity mode of thalamocortical networks observed during the sleep-wake cycle and on application of inhalational anesthetics.
authors.affiliation: Institute of Physiology, Otto-von-Guericke-Universität, D-39120 Magdeburg, Germany.
authors.forename: Sven G
authors.initials: SG
authors.lastname: Meuth
authors.forename: Thomas
authors.initials: T
authors.lastname: Budde
authors.forename: Tatyana
authors.initials: T
authors.lastname: Kanyshkova
authors.forename: Tilman
authors.initials: T
authors.lastname: Broicher
authors.forename: Thomas
authors.initials: T
authors.lastname: Munsch
authors.forename: Hans-Christian
authors.initials: HC
authors.lastname: Pape
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000494:pharmacology; D002045:Bupivacaine / Q000494:pharmacology; D005829:Geniculate Bodies / Q000378:metabolism; D006221:Halothane / Q000494:pharmacology; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D024683:Potassium Channels, Tandem Pore Domain; D051381:Rats; D020318:Rats, Long-Evans; D011976:Receptors, Muscarinic / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012890:Sleep / Q000502:physiology; D013788:Thalamus / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D014795:Visual Pathways / Q000502:physiology; D014851:Wakefulness / Q000502:physiology
chemical_list: D018685:Anesthetics, Inhalation; C407082:Kcnk9 protein, rat; D009419:Nerve Tissue Proteins; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; D011976:Receptors, Muscarinic; C420132:potassium channel subfamily K member 3; D001464:Barium; D011188:Potassium; D006221:Halothane; D002045:Bupivacaine