QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: mol.105.020594v1 mol.105.020594v2 mol.105.020594v3 69/4/1468    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Meuth, S. G. Articles by Budde, T. Search for Related Content PubMed PubMed Citation Articles by Meuth, S. G. Articles by Budde, T.

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

Institut für Experimentelle Epilepsieforschung, Westfälische Wilhelms-Universität Münster, Münster, Germany (T.B., H.-C.P.); Abteilung für Klinische Neurobiologie, Universität Heidelberg, Heidelberg, Germany (M.I.A., W.W.); Institut für Physiologie, Otto-von-Guericke-Universität, Magdeburg, Germany (T.M.); Institut für Physiologie I, Westfälische Wilhelms-Universität Münster, Münster, Germany (T.Se., H.-C.P.); Klinik für Neurologie, Julius-Maximilians-Universität Würzburg, Würzburg, Germany (S.G.M., T.Sc., C.K., H.W.); and Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, Scotland, United Kingdom (W.W.)

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 (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 µM), of muscarine (50 µM), 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 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 I_SO in DLG TC neurons, although the genetic knockout of TASK-1 did not produce severe deficits in the thalamocortical system.

Address correspondence to: Dr. Thomas Budde, Institut für Experimentelle Epilepsieforschung, Westfälische Wilhelms-Universität Münster, Hüfferstr. 68, D-48149 Münster, Germany. E-mail: tbudde{at}uni-muenster.de

This article has been cited by other articles:

				A.-M. Linden, M. I. Aller, E. Leppa, P. H. Rosenberg, W. Wisden, and E. R. Korpi K+ Channel TASK-1 Knockout Mice Show Enhanced Sensitivities to Ataxic and Hypnotic Effects of GABAA Receptor Ligands J. Pharmacol. Exp. Ther., October 1, 2008; 327(1): 277 - 286. [Abstract] [Full Text] [PDF]

				D. Heitzmann and R. Warth Physiology and Pathophysiology of Potassium Channels in Gastrointestinal Epithelia Physiol Rev, July 1, 2008; 88(3): 1119 - 1182. [Abstract] [Full Text] [PDF]

				S. G. Meuth, S. Bittner, P. Meuth, O. J. Simon, T. Budde, and H. Wiendl TWIK-related Acid-sensitive K+ Channel 1 (TASK1) and TASK3 Critically Influence T Lymphocyte Effector Functions J. Biol. Chem., May 23, 2008; 283(21): 14559 - 14570. [Abstract] [Full Text] [PDF]

				D. K. Mulkey, E. M. Talley, R. L. Stornetta, A. R. Siegel, G. H. West, X. Chen, N. Sen, A. M. Mistry, P. G. Guyenet, and D. A. Bayliss TASK Channels Determine pH Sensitivity in Select Respiratory Neurons But Do Not Contribute to Central Respiratory Chemosensitivity J. Neurosci., December 19, 2007; 27(51): 14049 - 14058. [Abstract] [Full Text] [PDF]

				A.-M. Linden, C. Sandu, M. I. Aller, O. Y. Vekovischeva, P. H. Rosenberg, W. Wisden, and E. R. Korpi TASK-3 Knockout Mice Exhibit Exaggerated Nocturnal Activity, Impairments in Cognitive Functions, and Reduced Sensitivity to Inhalation Anesthetics J. Pharmacol. Exp. Ther., December 1, 2007; 323(3): 924 - 934. [Abstract] [Full Text] [PDF]

				S. G. Brickley, M. I. Aller, C. Sandu, E. L. Veale, F. G. Alder, H. Sambi, A. Mathie, and W. Wisden TASK-3 Two-Pore Domain Potassium Channels Enable Sustained High-Frequency Firing in Cerebellar Granule Neurons J. Neurosci., August 29, 2007; 27(35): 9329 - 9340. [Abstract] [Full Text] [PDF]

				A. P. Berg and D. A. Bayliss Striatal Cholinergic Interneurons Express a Receptor-Insensitive Homomeric TASK-3-Like Background K+ Current J Neurophysiol, February 1, 2007; 97(2): 1546 - 1552. [Abstract] [Full Text] [PDF]

				J. Su, L. Yang, X. Zhang, A. Rojas, Y. Shi, and C. Jiang High CO2 chemosensitivity versus wide sensing spectrum: a paradoxical problem and its solutions in cultured brainstem neurons J. Physiol., February 1, 2007; 578(3): 831 - 841. [Abstract] [Full Text] [PDF]

				S. G. Meuth, T. Kanyshkova, P. Meuth, P. Landgraf, T. Munsch, A. Ludwig, F. Hofmann, H.-C. Pape, and T. Budde Membrane Resting Potential of Thalamocortical Relay Neurons Is Shaped by the Interaction Among TASK3 and HCN2 Channels J Neurophysiol, September 1, 2006; 96(3): 1517 - 1529. [Abstract] [Full Text] [PDF]