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.