Increased persistent sodium currents in rat entorhinal cortex layer V neurons in a post-status epilepticus model of temporal lobe epilepsy.
OBJECTIVE
Spontaneous seizures in rats emerge several weeks after induction of status epilepticus with pharmacologic treatment or electrical stimulation, providing an animal model for human temporal lobe epilepsy. In this study, we investigated whether status epilepticus caused changes in the function of voltage-gated sodium channels in entorhinal cortex layer V neurons, a cellular group important for the genesis of limbic seizures.


METHODS
We induced status epilepticus in rats, by using lithium-pilocarpine, and then 2-12 weeks later, used whole-cell voltage-clamp to examine voltage-activated sodium currents of acutely dissociated layer V neurons.


RESULTS
Transient sodium currents of entorhinal cortex layer V neurons isolated from 9- to 12-week post-status epilepticus rats were similar to currents in age-matched controls; however, low-threshold persistent sodium currents were significantly larger. This increase in persistent activity was not seen 2-3 weeks after pilocarpine treatment; thus it occurred after a delay comparable to the delay in the appearance of spontaneous seizures.


CONCLUSIONS
Increased persistent currents are expected to accentuate neuronal excitability and thus may contribute to the genesis of spontaneous seizures after status epilepticus.
Agrawal
Newton
N
Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec H3A 2B4, Canada.
Alonso
Angel
A
Ragsdale
David S
DS
D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D018728:Entorhinal Cortex / Q000187:drug effects / Q000503:physiopathology*; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000503:physiopathology*; D007696:Kindling, Neurologic / Q000502:physiology; D018021:Lithium Chloride; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D010862:Pilocarpine; D051381:Rats; D020318:Rats, Long-Evans; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*; D013226:Status Epilepticus / Q000139:chemically induced / Q000503:physiopathology*
D015222:Sodium Channels; D010862:Pilocarpine; D018021:Lithium Chloride