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The Journal of Neuroscience, July 1, 1998, 18(13):4842-4853
On the Action of the Anti-Absence Drug Ethosuximide in the Rat and Cat Thalamus
Nathalie Leresche2, H. Rheinallt Parri1, Gül Erdemli1, Alice Guyon2, Jonathan P. Turner1, Stephen R. Williams1, Eftihia Asprodini1, and Vincenzo Crunelli1 1 Physiology Unit, School of Molecular and Medical Biosciences, University of Wales Cardiff, Cardiff CF1 1SS, United Kingdom, and 2 Institut des Neurosciences, Centre National de la Recherche Scientifique, UMR 7624 Université Pierre et Marie Curie, Paris, France
The action of ethosuximide (ETX) on Na+, K+, and Ca2+ currents and on tonic and burst-firing patterns was investigated in rat and cat thalamic neurons in vitro by using patch and sharp microelectrode recordings. In thalamocortical (TC) neurons of the rat dorsal lateral geniculate nucleus (LGN), ETX (0.75-1 mM) decreased the noninactivating Na+ current, INaP, by 60% but had no effect on the transient Na+ current. In TC neurons of the rat and cat LGN, the whole-cell transient outward current was not affected by ETX (up to 1 mM), but the sustained outward current was decreased by 39% at 20 mV in the presence of ETX (0.25-0.5 mM): this reduction was not observed in a low Ca2+ (0.5 mM) and high Mg2+ (8 mM) medium or in the presence of Ni2+ (1 mM) and Cd2+ (100 µM). In addition, ETX (up to 1 mM) had no effect on the low-threshold Ca2+ current, IT, of TC neurons of the rat ventrobasal (VB) thalamus and LGN and in neurons of the rat nucleus reticularis thalami nor on the high-threshold Ca2+ current in TC neurons of the rat LGN.
Sharp microelectrode recordings in TC neurons of the rat and cat LGN and VB showed that ETX did not change the resting membrane potential but increased the apparent input resistance at potentials greater than
60 mV, resulting in an increase in tonic firing. In contrast, ETX decreased the number of action potentials in the burst evoked by a low-threshold Ca2+ potential. The frequency of the remaining action potentials in a burst also was decreased, whereas the latency of the first action potential was increased. Similar effects were observed on the burst firing evoked during intrinsic
oscillations.
These results indicate an action of ETX on INaP and on the Ca2+-activated K+ current, which explains the decrease in burst firing and the increase in tonic firing, and, together with the lack of action on low- and high-threshold Ca2+ currents, the results cast doubts on the hypothesis that a reduction of IT in thalamic neurons underlies the therapeutic action of this anti-absence medicine.
Key words: ethosuximide; thalamus; Na+ currents; K+ currents; Ca2+ currents; tonic firing; burst firing; absence epilepsy
Copyright © 1998 Society for Neuroscience 0270-6474/98/18134842-12$05.00/0
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