Effects of zonisamide on K+ and Ca2+ evoked release of monoamine as well as K+ evoked intracellular Ca2+ mobilization in rat hippocampus.
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.
Department of Neuropsychiatry, Hirosaki University, Japan.
Y
Y
Kawata
M
M
Okada
T
T
Murakami
K
K
Mizuno
K
K
Wada
T
T
Kondo
S
S
Kaneko
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D015306:Biogenic Monoamines / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007091:Image Processing, Computer-Assisted; D007555:Isoxazoles / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology; D000078305:Zonisamide
D000927:Anticonvulsants; D015306:Biogenic Monoamines; D007555:Isoxazoles; D012701:Serotonin; D000078305:Zonisamide; D011188:Potassium; D002118:Calcium; D004298:Dopamine