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Title: Rat epileptic seizures evoked by BmK {alpha}IV and its possible mechanisms involved in sodium channels

Journal Article · · Toxicology and Applied Pharmacology
 [1];  [1];  [1];  [1];  [2];  [2]
  1. Graduate School of the Chinese Academy of Sciences, Shanghai Institute of Physiology, Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China)
  2. School of Life Sciences of Shanghai University, Shang-Da Road 99, Shanghai 200444 (China)

This study showed that rat unilateral intracerebroventricular injection of BmK {alpha}IV, a sodium channel modulator derived from scorpion Buthus martensi Karsch, induced clusters of spikes, epileptic discharges and convulsion-related behavioral changes. BmK {alpha}IV potently promoted the release of endogenous glutamate from rat cerebrocortical synaptosomes. In vitro examination of the effect of BmK {alpha}IV on intrasynaptosomal free calcium concentration [Ca{sup 2+}]{sub i} and sodium concentration [Na{sup +}]{sub i} revealed that BmK {alpha}IV-evoked glutamate release from synaptosomes was associated with an increase in Ca{sup 2+} and Na{sup +} influx. Moreover, BmK {alpha}IV-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 {alpha}IV-evoked epileptic seizures may be involved in the modulation of BmK {alpha}IV on tetrodotoxin-sensitive sodium channels located on the nerve terminal, which subsequently enhances the Ca{sup 2+} influx to cause an increase of glutamate release. These findings may provide some insight regarding the mechanism of neuronal action of BmK {alpha}IV in the central nervous system for understanding epileptogenesis involved in sodium channels.

OSTI ID:
20976914
Journal Information:
Toxicology and Applied Pharmacology, Vol. 220, Issue 3; Other Information: DOI: 10.1016/j.taap.2007.01.006; PII: S0041-008X(07)00022-1; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0041-008X
Country of Publication:
United States
Language:
English

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