Periodicity of thalamic spindle waves is abolished by ZD7288,a blocker of Ih

Journal of Neurophysiology
A LüthiD A McCormick

Abstract

The actions of the novel bradycardiac agent ZD7288 [4-(N-ethyl-N-phenylamino)-1, 2-dimethyl-6-(methylamino)pyrimidinium chloride] were investigated on the hyperpolarization-activated cation current Ih and on network activity in spontaneously spindling ferret lateral geniculate (LGNd) slices in vitro using intracellular recording techniques. In voltage-clamp recordings, local application of ZD7288 (1 mM in micropipette) resulted in a complete block of Ih, whereas in current-clamp recordings, application of this agent resulted in an abolition of the depolarizing sag activated by hyperpolarization and decreased the frequency of intrinsic delta-oscillations for which Ih acts as a pacemaker current. In addition, block of Ih with ZD7288 resulted in an abolition of the afterdepolarization (ADP) that follows repetitive hyperpolarization and rebound burst firing as well as that occurring in between spindle waves. The block of the ADP was associated with a block of the spindle wave refractory period such that continuous 6- to 10-Hz oscillations were generated throughout the network. These findings give further support to the hypothesis that Ih is critically involved in the generation of slow rhythmicity in synchronized thalamic activity.

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Citations

Sep 25, 2003·Physiological Reviews·A Destexhe, T J Sejnowski
Apr 23, 2005·The European Journal of Neuroscience·Günter GisselmannHanns Hatt
May 14, 2008·Proceedings of the National Academy of Sciences of the United States of America·Milena WinogradMaria V Sanchez-Vives
Sep 8, 2012·Journal of Neurophysiology·Patricio OrioFélix Viana
Mar 11, 2004·Journal of Neurophysiology·T KobayashiE Garcia-Rill
Sep 4, 2015·Physiology·Aklesso KadalaArlette Kolta
Dec 6, 2019·Physiological Reviews·Laura M J Fernandez, Anita Lüthi
Jul 22, 1999·Annals of the New York Academy of Sciences·A Lüthi, D A McCormick
Sep 4, 2004·Epilepsy Currents·Nicholas P. Poolos
May 20, 2005·Epilepsy Currents·Douglas A Coulter
Jul 15, 1999·Nature Neuroscience·A Lüthi, D A McCormick
Feb 22, 2001·Annual Review of Physiology·D A McCormick, D Contreras
Jun 3, 2010·Journal of Computational Neuroscience·Cheng LyG Bard Ermentrout
Sep 30, 2005·Journal of Neurophysiology·Aldo Rogelis A Rodrigues, Donata Oertel
Sep 25, 2009·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Bi-Wen PengRussell M Sanchez
May 10, 2018·Frontiers in Cellular Neuroscience·Przemysław KurowskiPaweł Szulczyk
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Jan 20, 2006·Synapse·Catherine H GillCeri H Davies
Nov 27, 2020·Psychopharmacology·María Celeste Rivero-EchetoFrancisco J Urbano

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