1. Rat epileptic seizures evoked by BmK alphaIV and its possible mechanisms involved in sodium channels.
- Author
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Chai ZF, Bai ZT, Zhang XY, Liu T, Pang XY, and Ji YH
- Subjects
- Animals, Calcium chemistry, Calcium metabolism, Cerebral Cortex drug effects, Cerebral Cortex metabolism, Dose-Response Relationship, Drug, Electroencephalography drug effects, Electrophysiology, Epilepsy chemically induced, Fluorometry methods, Glutamic Acid metabolism, Injections, Intraventricular, Male, Potassium Chloride toxicity, Rats, Rats, Sprague-Dawley, Scorpion Venoms administration & dosage, Sodium chemistry, Sodium metabolism, Sodium Channel Blockers toxicity, Synaptosomes drug effects, Synaptosomes metabolism, Tetrodotoxin toxicity, Time Factors, Epilepsy physiopathology, Scorpion Venoms toxicity, Sodium Channels physiology
- Abstract
This study showed that rat unilateral intracerebroventricular injection of BmK alphaIV, a sodium channel modulator derived from scorpion Buthus martensi Karsch, induced clusters of spikes, epileptic discharges and convulsion-related behavioral changes. BmK alphaIV potently promoted the release of endogenous glutamate from rat cerebrocortical synaptosomes. In vitro examination of the effect of BmK alphaIV on intrasynaptosomal free calcium concentration [Ca(2+)](i) and sodium concentration [Na(+)](i) revealed that BmK alphaIV-evoked glutamate release from synaptosomes was associated with an increase in Ca(2+) and Na(+) influx. Moreover, BmK alphaIV-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 alphaIV-evoked epileptic seizures may be involved in the modulation of BmK alphaIV on tetrodotoxin-sensitive sodium channels located on the nerve terminal, which subsequently enhances the Ca(2+) influx to cause an increase of glutamate release. These findings may provide some insight regarding the mechanism of neuronal action of BmK alphaIV in the central nervous system for understanding epileptogenesis involved in sodium channels.
- Published
- 2007
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