Computer model of ethosuximide's effect on a thalamic neuron.
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 depolarizing 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.
Lytton
W W
WW
Salk Institute, La Jolla, CA 92037.
Sejnowski
T J
TJ
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000502:physiology; D003198:Computer Simulation; D005013:Ethosuximide / Q000494:pharmacology*; D008959:Models, Neurological; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D013788:Thalamus / Q000187:drug effects* / Q000502:physiology
D005013:Ethosuximide; D002118:Calcium