Extracellular magnesium and anticonvulsant effects of valproate in young rat hippocampus.
Extracellular field potential recordings were made in CA3 subfield of hippocampal slices from rats aged 11-22 days. In these experiments, we analyzed the effects induced by modifying [Mg2+] in the medium (1 or 2 mM) on (a) 4-aminopyridine (4-AP, 50 microM)-induced synchronous events (including ictal- and interictal-like epileptiform discharges as well as gamma-aminobutyric acid (GABA)-mediated potentials), and (b) the changes induced by the antiepileptic drug (AED) valproate (VPA 2 mM) on such activities. Changing [Mg2+] from 1 to 2 mM induced age-dependent effects consisting of reduction in rate of occurrence of ictal-like discharges at 11-13 days (55% reduction, p < 0.005) and 14-16 days (46% reduction, p < 0.025) postpartum. At any age, the rate of occurrence and the amplitude of the GABA-mediated synchronous potentials tended to decrease in 1 mM [Mg2+]. Similar effects were noted when changes in [Mg2+] were made during continuous application of the competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor DL-2-amino-5-phosphonovalerate (APV 50 microM). As previously reported, interictal and ictal discharges were blocked by addition of VPA to medium containing 2 mM [Mg2+]. Such an effect was not observed when [Mg2+] was decreased to 1 mM. In 1 mM, but not in 2 mM [Mg2+], VPA increased the amplitude of GABA-mediated synchronous potentials. Our results indicate that [Mg2+] plays a role in modulating occurrence of 4-AP-induced ictal activity and that it can influence the effects of VPA in this in vitro model of epileptogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)
Fueta
Y
Y
Montreal Neurological Institute, McGill University, Quebec, Canada.
Siniscalchi
A
A
Tancredi
V
V
Avoli
M
M
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D004827:Epilepsy / Q000139:chemically induced* / Q000517:prevention & control; D006624:Hippocampus / Q000187:drug effects*; D007476:Ionophores; D008274:Magnesium / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D014635:Valproic Acid / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D007476:Ionophores; D016194:Receptors, N-Methyl-D-Aspartate; D005680:gamma-Aminobutyric Acid; D014635:Valproic Acid; D015763:2-Amino-5-phosphonovalerate; D015761:4-Aminopyridine; D008274:Magnesium