Interaction between Ca2+, K+, carbamazepine and zonisamide on hippocampal extracellular glutamate monitored with a microdialysis electrode
Version of Record online: 11 FEB 2009
1998 British Pharmacological Society
British Journal of Pharmacology
Volume 124, Issue 6, pages 1277–1285, July 1998
How to Cite
Okada, M., Kawata, Y., Mizuno, K., Wada, K., Kondo, T. and Kaneko, S. (1998), Interaction between Ca2+, K+, carbamazepine and zonisamide on hippocampal extracellular glutamate monitored with a microdialysis electrode. British Journal of Pharmacology, 124: 1277–1285. doi: 10.1038/sj.bjp.0701941
- Issue online: 11 FEB 2009
- Version of Record online: 11 FEB 2009
- (Received April 14, 1998, Accepted April 16, 1998)
- microdialysis electrode;
- spreading depression;
- 1Multiple 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.
- 2Basal glutamate levels were below detection limits (∼0.1 μm). 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 μm, respectively, calculated from the area under curve (AUC) for 60 min.
- 3This KCl-evoked glutamate release consisted of three components: an initial transient rise, a late gentle rise, and late multiple phasic transient rises.
- 4An 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 μm.
- 5Perfusion with 100 μm 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 μm, respectively, as well as the stimulatory effects of Ca2+ on KCl-evoked hippocampal glutamate release.
- 6These results suggest that both CBZ and ZNS may reduce epileptiform events by inhibiting excitatory glutamatergic transmission.
British Journal of Pharmacology (1998) 124, 1277–1285; doi:10.1038/sj.bjp.0701941