omega-Conotoxin MVIIA inhibits amygdaloid kindled seizures in Sprague-Dawley rats.
omega-Conotoxin MVIIA (omega-CTX MVIIA) is a reversible and potent antagonist of N-type voltage-dependent calcium channels (VDCCs) in neurons. In this study, we evaluated the effect of a fusion form of omega-CTX MVIIA with glutathione S-transferase (GST) on amygdaloid kindled seizures. Intracerebraventricular (i.c.v.) injection of the fusion protein of GST-omega-CTX MVIIA significantly decreased seizure stage and shortened afterdischarge duration and generalized seizure duration in a dose-dependent and time-related manner. In addition, GST-omega-CTX MVIIA significantly increased the GABA levels in the cortex and glycine levels in the brainstem. In contrast, GST alone did not have any effect on seizure behavior or neurochemical levels. These findings firstly demonstrate that the N-type VDCC is a potential therapeutic target for temporal lobe epilepsy. The mechanism of the anticonvulsant function of omega-CTX MVIIA is related to the blockade of N-type VDCC-mediated neurotransmitter release in the brain.
Wang
Shuang
S
Department of Pharmacology and Biochemistry, School of Medicine, Zhejiang University, Hangzhou 310058, China.
Ding
Meiping
M
Wu
Dengchang
D
Zhan
Jinbiao
J
Chen
Zhong
Z
D000679:Amygdala / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020864:Calcium Channels, N-Type / Q000187:drug effects / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004833:Epilepsy, Temporal Lobe / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D005982:Glutathione Transferase / Q000187:drug effects / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D007696:Kindling, Neurologic / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism; D020960:omega-Conotoxins / Q000494:pharmacology*
D000927:Anticonvulsants; D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D020960:omega-Conotoxins; D005680:gamma-Aminobutyric Acid; C078452:ziconotide; D005982:Glutathione Transferase; D005998:Glycine