Is the persistent sodium current a specific target of anti-absence drugs?

The persistent Na+ current (I-NaP) has been proposed as the putative target of the anti-absence antiepileptic drugs. Accordingly, the effect of reference anti-absence drugs ethosuximide (ESM) and valproate (VPA), and of the new antiepileptic drug levetiracetam (LEV), on I-NaP have been tested in CAI hippocampal neurons and compared to the classic anticonvulsant phenytoin (PHT) and the neuroprotective agent riluzole (RIL). Whole-cell patch-clamp recordings of the slowly inactivating current, fully characterized as I-NaP, were performed with a standard voltage-step protocol on thin hippocampal slices prepared from rat brain. Both PHT (100 muM) and RIL (10 muM) strongly depressed I-NaP, whereas ESM (1 mM) induced a slight decrease Of I-NaP and VPA (1 mM) had no effect. Likewise, 60-min perfusion with relevant concentrations of LEV (10, 32 or 100 muM) did not modify I-NaP. In conclusion, these data question the impact Of I-NaP depression as an anti-absence mechanism, and also discalim the involvement of I-NaP in the antiepileptic mechanism of LEV.