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Veratridine, But Not Elevated K + , Inhibits Excitatory Amino Acid Transporter Activity in Rat Hippocampal Slices
Author(s) -
Claudio O. I.,
Berríos N.,
García M.,
Casasnovas R.,
Ortiz J. G.
Publication year - 2002
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1046/j.1528-1157.43.s.5.5.x
Subject(s) - veratridine , hippocampal formation , excitatory postsynaptic potential , excitatory amino acid transporter , chemistry , neuroscience , transporter , endocrinology , medicine , biochemistry , biology , sodium , sodium channel , receptor , organic chemistry , gene
Summary: Purpose: Excitatory amino acid transporter (EAAT) activity prevents Glu from reaching toxic levels, but their contribution to epileptogenesis remains controversial. We examined how the convulsant veratridine causes inhibition of EAAT activity and how it differs from the effects of another convulsant, high (50 m M ) K + , that also increases Na + conductance. Methods: Transverse rat hippocampal slices were incubated for 1 h with 100 μ M veratridine in oxygenated artificial cerebrospinal fluid (aCSF) with or without extracellular Ca 2+ . The medium was replaced by 50 μ M [ 3 H]glutamate in aCSF, and the slices incubated for 10 min at 37°C. The slices were washed 3 times with cold aCSF after removal of the extracellular medium, and the radioactivity was quantified after solubilization of the slices. Results: Veratridine caused a time‐ and dose‐dependent decrease, whereas high K + had no effect on EAAT activity. The effects of veratridine on EAAT activity were not prevented by tetrodotoxin (TTX; 10 μ M ). Coincubation of ouabain with veratridine resulted in further decreases of EAAT activity. Removal of extracellular Ca 2+ potentiated the inhibitory effects of veratridine (and other convulsants) on EAAT activity. Chelation of intracellular Ca 2+ with BAPTA also increased the inhibitory effects of veratridine on EAAT activity. Conclusions: Veratridine caused changes Ca 2+ dynamics that led to inhibition of EAAT activity. Such changes in EAAT activity can contribute to the sustained epileptiform activity caused by veratridine.