Veratridine, but not elevated K+, inhibits excitatory amino acid transporter activity in rat hippocampal slices.
OBJECTIVE
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 mM) K+, that also increases Na+ conductance.


METHODS
Transverse rat hippocampal slices were incubated for 1 h with 100 microM veratridine in oxygenated artificial cerebrospinal fluid (aCSF) with or without extracellular Ca2+. The medium was replaced by 50 microM[(3)H]glutamate in aCSF, and the slices incubated for 10 min at 37 degrees 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 microM). Coincubation of ouabain with veratridine resulted in further decreases of EAAT activity. Removal of extracellular Ca2+ potentiated the inhibitory effects of veratridine (and other convulsants) on EAAT activity. Chelation of intracellular Ca2+ with BAPTA also increased the inhibitory effects of veratridine on EAAT activity.


CONCLUSIONS
Veratridine caused changes Ca2+ dynamics that led to inhibition of EAAT activity. Such changes in EAAT activity can contribute to the sustained epileptiform activity caused by veratridine.
Department of Pharmacology and Toxicology, University of Puerto Rico School of Medicine, San Juan, Puerto Rico 00936-5067.
O I
OI
Claudio
N
N
Berríos
M
M
García
R
R
Casasnovas
J G
JG
Ortiz
D026905:Amino Acid Transport Systems / Q000037:antagonists & inhibitors*; D000818:Animals; D003292:Convulsants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006624:Hippocampus / Q000378:metabolism*; D066298:In Vitro Techniques; D011188:Potassium / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014701:Veratridine / Q000494:pharmacology*
D026905:Amino Acid Transport Systems; D003292:Convulsants; D014701:Veratridine; D011188:Potassium