Computer model of ethosuximide's effect on a thalamic neuron

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Abstract
Ethosuximide appears to have a specific effect on the low‐threshold calcium current in thalamic cells. This may be related to its efficacy in the treatment of absence epilepsy. We used a computer model of an individual thalamocortical neuron to better understand the alteration in the low‐threshold calcium current under voltage clamp and to predict response to current injection in the presence of ethosuximide. The full model included nine voltage‐sensitive ionic channels and a realistic dendritic morphology. The model reproduced the two major responses seen in tissue slices: repetitive spiking with depolarization and the low‐threshold calcium spike elicited on release from hyperpolarization. The alteration in low‐threshold calcium current with ethosuximide can be explained by a 10‐mV depolariting shift in the steady‐state activation curve for this channel with a 10% reduction in maximum channel permeability. Simulations of current injection showed that ethosuximide diminished the low‐threshold calcium spike while leaving the tonic firing pattern unaffected. Our results support the hypothesis that ethosuximide's effects on low‐threshold calcium current might selectively alter the dynamics of slow bursting in thalamic cells.