Effects of zonisamide on K+ and Ca2+ evoked release of monoamine as well as K+ evoked intracellular Ca2+ mobilization in rat hippocampus

• Published in: Epilepsy research 1999-07, Vol.35 (3), p.173-182
• Main Authors: KAWATA, Y, OKADA, M, MURAKAMI, T, MIZUNO, K, WADA, K, KONDO, T, KANEKO, S
• Format: Article
• Language: English
• Subjects: Animals; Anticonvulsants - pharmacology; Anticonvulsants. Antiepileptics. Antiparkinson agents; Biogenic Monoamines - metabolism; Biological and medical sciences; Calcium - metabolism; Calcium - pharmacology; Chromatography, High Pressure Liquid; Dopamine - metabolism; Hippocampus - drug effects; Hippocampus - metabolism; Image Processing, Computer-Assisted; Isoxazoles - pharmacology; Male; Medical sciences; Microdialysis; Neuropharmacology; Pharmacology. Drug treatments; Potassium - pharmacology; Rats; Rats, Wistar; Serotonin - metabolism; Synaptic Transmission - physiology
• ISSN: 0920-1211; 1872-6844
• DOI: 10.1016/s0920-1211(99)00010-8

To clarify the effects of zonisamide (ZNS) on neurotransmission and intracellular Ca2+ mobilization, both Ca2+ and K+ evoked hippocampal releases of dopamine (DA) and serotonin (5-HT) were determined by in vivo microdialysis, and K+ (25 and 50 mM) evoked elevation of intracellular Ca2+ level was determined by fluorescence microscopy in vitro. Therapeutic concentrations of ZNS had different effects on Ca2+ and K+ evoked release of monoamine. ZNS stimulated Ca2+ evoked monoamine release, while ZNS inhibited K+ evoked monoamine release. ZNS inhibited K+ evoked elevation of hippocampal intracellular Ca2+ levels in a concentration dependent manner. These results suggest that ZNS inhibits the depolarization induced by neuronal excitation, whereas ZNS might enhance the N-type Ca2+ channel activity or N-type Ca2+ channel related exocytosis mechanisms.