title: Characterization of ethosuximide reduction of low-threshold calcium current in thalamic neurons.
abstract: The mechanism by which ethosuximide reduces thalamic low-threshold calcium current (LTCC) was analyzed using voltage-clamp techniques in acutely isolated ventrobasal complex neurons from rats and guinea pigs. The ethosuximide-induced reduction of LTCC was voltage dependent: it was most pronounced at more-hyperpolarized potentials and did not affect the time course of activation or inactivation of the current. Ethosuximide reduced LTCC without altering the voltage dependence of steady-state inactivation or the time course of recovery from inactivation. Dimethadione reduced LTCC by a similar mechanism, while valproic acid had no effect on LTCC. We conclude that ethosuximide reduction of LTCC in thalamic neurons is consistent with a reduction in the number of available LTCC channels or in the single LTCC channel conductance, perhaps indicating a direct channel-blocking action of this drug. Given the importance of LTCC in thalamic oscillatory behavior, a reduction in this current by ethosuximide would be a mechanism of action compatible with the known anticonvulsant effects of this drug in typical absence seizures.
authors.affiliation: Department of Neurology, Stanford University Medical Center, CA 94305.
authors.forename: D A
authors.initials: DA
authors.lastname: Coulter
authors.forename: J R
authors.initials: JR
authors.lastname: Huguenard
authors.forename: D A
authors.initials: DA
authors.lastname: Prince
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000187:drug effects; D004114:Dimethadione / Q000494:pharmacology; D005013:Ethosuximide / Q000494:pharmacology*; D006168:Guinea Pigs; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D013788:Thalamus / Q000166:cytology* / Q000187:drug effects; D014635:Valproic Acid / Q000494:pharmacology
chemical_list: D015220:Calcium Channels; D005013:Ethosuximide; D014635:Valproic Acid; D004114:Dimethadione