Rat epileptic seizures evoked by BmK alphaIV and its possible mechanisms involved in sodium channels.
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.
Chai
Zhi-Fang
ZF
Graduate School of the Chinese Academy of Sciences, Shanghai Institute of Physiology, Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, PR China.
Bai
Zhan-Tao
ZT
Zhang
Xu-Ying
XY
Liu
Tong
T
Pang
Xue-Yan
XY
Ji
Yong-Hua
YH
D000818:Animals; D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000187:drug effects; D004594:Electrophysiology; D004827:Epilepsy / Q000139:chemically induced / Q000503:physiopathology*; D005470:Fluorometry / Q000379:methods; D018698:Glutamic Acid / Q000378:metabolism; D007276:Injections, Intraventricular; D008297:Male; D011189:Potassium Chloride / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012604:Scorpion Venoms / Q000008:administration & dosage / Q000633:toxicity*; D012964:Sodium / Q000737:chemistry / Q000378:metabolism; D026941:Sodium Channel Blockers / Q000633:toxicity; D015222:Sodium Channels / Q000502:physiology*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D013779:Tetrodotoxin / Q000633:toxicity; D013997:Time Factors
C514521:BmK alpha IV toxin, Buthus martensi Karsch; D012604:Scorpion Venoms; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D018698:Glutamic Acid; D013779:Tetrodotoxin; D011189:Potassium Chloride; D012964:Sodium; D002118:Calcium