High-affinity inhibition of glutamate release from corticostriatal synapses by omega-agatoxin TK.
To know which Ca(2+) channel type is the most important for neurotransmitter release at corticostriatal synapses of the rat, we tested Ca(2+) channel antagonists on the paired pulse ratio. omega-Agatoxin TK was the most effective Ca(2+) channel antagonist (IC(50)=127 nM; maximal effect=211% (with >1 microM) and Hill coefficient=1.2), suggesting a single site of action and a Q-type channel profile. Corresponding parameters for Cd(2+) were 13 microM, 178% and 1.2. The block of L-type Ca(2+) channels had little impact on transmission, but we also tested facilitation of L-type Ca(2+) channels. The L-type Ca(2+) channel agonist, s-(-)-1,4 dihydro-2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)phenyl]-3-pyridine carboxylic acid methyl ester (Bay K 8644 (5 microM)), produced a 45% reduction of the paired pulse ratio, suggesting that even if L-type channels do not participate in the release process, they may participate in its modulation.
Barral
J
J
Neurociencias, FES Iztacala, UNAM, Estado de Mexico, Mexico.
Poblette
F
F
Mendoza
E
E
Pineda
J C
JC
Galarraga
E
E
Bargas
J
J
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D060848:Agatoxins; D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000502:physiology; D003342:Corpus Striatum / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013111:Spider Venoms / Q000494:pharmacology*; D013569:Synapses / Q000187:drug effects* / Q000378:metabolism; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
D060848:Agatoxins; D002121:Calcium Channel Blockers; D013111:Spider Venoms; C083855:omega-agatoxin-Aa4b; D002104:Cadmium; D018698:Glutamic Acid; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D020866:omega-Conotoxin GVIA; D002118:Calcium