Characterization of ethosuximide reduction of low-threshold calcium current in thalamic neurons

✍ Scribed by Dr. Douglas A. Coulter; John R. Huguenard; David A. Prince

• Publisher: John Wiley and Sons
• Year: 1989
• Tongue: English
• Weight: 1016 KB
• Volume: 25
• Category: Article
• ISSN: 0364-5134
• DOI: 10.1002/ana.410250610

✦ Synopsis

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.