| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 4326309 | Brain Research | 2010 | 6 Pages |
Recent evidence suggests that the sodium calcium exchanger (NCX) may contribute to the etiology of pentylenetetrazol-induced seizures. Here we further investigated the role of NCX in the etiology of seizures by quantifying the effects of KB-R7943 and SN-6, potent inhibitors of the reverse mode of NCX subtypes 3 (NCX3) and 1 (NCX1), respectively, on the occurrence of acute seizures and status epilepticus induced by intraperitoneal administration of pilocarpine, a muscarinic acetylcholine receptor agonist. Pretreatment with KB-R7943 significantly reduced the incidence of pilocarpine-induced seizures and status epilepticus in 22–56% of treated animals. In the remaining animals that exhibited seizures, KB-R7943 pretreatment delayed the onset of seizures and status epilepticus, and reduced seizure severity. Delayed onset of seizures and reduced seizure severity also were seen following pretreatment with SN-6. These findings suggest that altered NCX activity may contribute to the pathophysiology of pilocarpine-induced seizures and status epilepticus.
Research Highlights► Normal: NCX transports Ca2+ out and Na+ into the neuron. ► Pilocarpine-induced seizures: NCX transports Na+ out and Ca2+ into the neuron. ► NCX inhibitors: prevent Ca2+ entry and Na+ exit. ► Seizure suppression.
