 |
|||||
|
|||||
|
|||||
|
|||||
|
|||||
Previous Article | Next Article
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
This article has been cited by other articles:
M. A. Castro-Alamancos, P. Rigas, and Y. Tawara-Hirata
Resonance (~10 Hz) of excitatory networks in motor cortex: effects of voltage-dependent ion channel blockers
J. Physiol., January 1, 2007; 578(1): 173 - 191.
[Abstract] [Full Text] [PDF]
H. Khosravani and G. W. Zamponi
Voltage-gated calcium channels and idiopathic generalized epilepsies.
Physiol Rev, July 1, 2006; 86(3): 941 - 966.
[Abstract] [Full Text] [PDF]
R. R. Llinas and M. Steriade
Bursting of Thalamic Neurons and States of Vigilance
J Neurophysiol, June 1, 2006; 95(6): 3297 - 3308.
[Abstract] [Full Text] [PDF]
S. Remy and H. Beck
Molecular and cellular mechanisms of pharmacoresistance in epilepsy
Brain, January 1, 2006; 129(1): 18 - 35.
[Abstract] [Full Text] [PDF]
P. M Joksovic, D. A Bayliss, and S. M Todorovic
Different kinetic properties of two T-type Ca2+ currents of rat reticular thalamic neurones and their modulation by enflurane
J. Physiol., July 1, 2005; 566(1): 125 - 142.
[Abstract] [Full Text] [PDF]
I. Vitko, Y. Chen, J. M. Arias, Y. Shen, X.-R. Wu, and E. Perez-Reyes
Functional Characterization and Neuronal Modeling of the Effects of Childhood Absence Epilepsy Variants of CACNA1H, a T-Type Calcium Channel
J. Neurosci., May 11, 2005; 25(19): 4844 - 4855.
[Abstract] [Full Text] [PDF]
K. Evason, C. Huang, I. Yamben, D. F. Covey, and K. Kornfeld
Anticonvulsant Medications Extend Worm Life-Span
Science, January 14, 2005; 307(5707): 258 - 262.
[Abstract] [Full Text] [PDF]
Y. Zhang, A. P. Vilaythong, D. Yoshor, and J. L. Noebels
Elevated Thalamic Low-Voltage-Activated Currents Precede the Onset of Absence Epilepsy in the SNAP25-Deficient Mouse Mutant Coloboma
J. Neurosci., June 2, 2004; 24(22): 5239 - 5248.
[Abstract] [Full Text] [PDF]
D. M. Porcello, S. D. Smith, and J. R. Huguenard
Actions of U-92032, a T-Type Ca2+ Channel Antagonist, Support a Functional Linkage Between IT and Slow Intrathalamic Rhythms
J Neurophysiol, January 1, 2003; 89(1): 177 - 185.
[Abstract] [Full Text] [PDF]
E. Perez-Reyes
Molecular Physiology of Low-Voltage-Activated T-type Calcium Channels
Physiol Rev, January 1, 2003; 83(1): 117 - 161.
[Abstract] [Full Text] [PDF]
J. C. Gomora, A. N. Daud, M. Weiergraber, and E. Perez-Reyes
Block of Cloned Human T-Type Calcium Channels by Succinimide Antiepileptic Drugs
Mol. Pharmacol., November 1, 2001; 60(5): 1121 - 1132.
[Abstract] [Full Text] [PDF]
S. M. Todorovic, E. Perez-Reyes, and C. J. Lingle
Anticonvulsants But Not General Anesthetics Have Differential Blocking Effects on Different T-Type Current Variants
Mol. Pharmacol., July 1, 2000; 58(1): 98 - 108.
[Abstract] [Full Text]
S. M. Todorovic, M. Prakriya, Y. M. Nakashima, K. R. Nilsson, M. Han, C. F. Zorumski, D. F. Covey, and C. J. Lingle
Enantioselective Blockade of T-type Ca2+ Current in Adult Rat Sensory Neurons by a Steroid That Lacks gamma -Aminobutyric Acid-Modulatory Activity
Mol. Pharmacol., November 1, 1998; 54(5): 918 - 927.
[Abstract] [Full Text]
|
|
|
|
 |
|