Rat epileptic seizures evoked by BmK αIV and its possible mechanisms involved in sodium channels

This study showed that rat unilateral intracerebroventricular injection of BmK αIV, a sodium channel modulator derived from scorpion Buthus martensi Karsch, induced clusters of spikes, epileptic discharges and convulsion-related behavioral changes. BmK αIV potently promoted the release of endogenous glutamate from rat cerebrocortical synaptosomes. In vitro examination of the effect of BmK αIV on intrasynaptosomal free calcium concentration [Ca2+]i and sodium concentration [Na+]i revealed that BmK αIV-evoked glutamate release from synaptosomes was associated with an increase in Ca2+ and Na+ influx. Moreover, BmK αIV-mediated glutamate release and ion influx was completely blocked by tetrodotoxin, a blocker of sodium channel. Together, these results suggest that the induction of BmK αIV-evoked epileptic seizures may be involved in the modulation of BmK αIV on tetrodotoxin-sensitive sodium channels located on the nerve terminal, which subsequently enhances the Ca2+ influx to cause an increase of glutamate release. These findings may provide some insight regarding the mechanism of neuronal action of BmK αIV in the central nervous system for understanding epileptogenesis involved in sodium channels.