Interaction between Ca2+, K+, carbamazepine and zonisamide on hippocampal extracellular glutamate monitored with a microdialysis electrode.
1. Multiple components of hippocampal glutamate release were examined by study of Ca2+- and K+-evoked hippocampal extracellular glutamate release using an in vivo microdialysis glutamate biosensor in urethane-anaesthetized rats. In addition, the effects of the antiepileptic drugs, carbamazepine (CBZ) and zonisamide (ZNS) perfused through the probe on glutamate release were assessed. 2. Basal glutamate levels were below detection limits (approximately 0.1 microM). An increase in extracellular KCl (from 2.7 to 50 and 100 mM) increased extracellular hippocampal glutamate levels to 9.2+/-1.4 and 20.0+/-2.6 microM, respectively, calculated from the area under curve (AUC) for 60 min. 3. This KCl-evoked glutamate release consisted of three components: an initial transient rise, a late gentle rise, and late multiple phasic transient rises. 4. An increase in or removal of extracellular CaCl2 levels respectively enhanced and reduced the 50 mM KCl-evoked hippocampal glutamate release (AUC for 60 min) from 9.2+/-1.4 to 12.4+/-2.1 and 5.8+/-0.9 microM. 5. Perfusion with 100 microM CBZ or 1 mM ZNS inhibited both the 50 mM KCl-evoked hippocampal glutamate release (AUC for 60 min) from 9.2+/-1.4 to 5.5+/-1.1 and to 5.8+/-1.3 microM, respectively, as well as the stimulatory effects of Ca2+ on KCl-evoked hippocampal glutamate release. 6. These results suggest that both CBZ and ZNS may reduce epileptiform events by inhibiting excitatory glutamatergic transmission.
Department of Neuropsychiatry, Hirosaki University, Japan.
M
M
Okada
Y
Y
Kawata
K
K
Mizuno
K
K
Wada
T
T
Kondo
S
S
Kaneko
D000818:Animals; D000927:Anticonvulsants / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002220:Carbamazepine / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D007555:Isoxazoles / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D000078305:Zonisamide
D000927:Anticonvulsants; D007555:Isoxazoles; D002220:Carbamazepine; D018698:Glutamic Acid; D000078305:Zonisamide; D011188:Potassium; D002118:Calcium