title: omega-Agatoxin IVA identifies a single calcium channel subtype which contributes to the potassium-induced release of acetylcholine, 5-hydroxytryptamine, dopamine, gamma-aminobutyric acid and glutamate from rat brain slices.
abstract: The voltage-dependent calcium channels (VDCCs) involved in K(+)-induced transmitter release have been studied. A maximally effective concentration of the N-type VDCC inhibitor, omega-conotoxin GVIA (GVIA) blocked the release of 5-HT (30%), DA (30%) and ACh (60%) but not that of GABA or glutamate. The O, P and Q-type VDCC inhibitor, omega-agatoxin IVA (Aga IVA, 1 microM), blocked 100% of GABA and glutamate, 70% of DA and about 50% of 5-HT and ACh release. The slopes of the inhibiton curves indicate that it acts on the same, single type of VDCC in all cases. omega-Conotoxin MVIIC (MVIIC) completely inhibited the release of all the transmitters. It is concluded that a single GVIA-insensitive type of VDCC is involved in the K(+)-induced release of all the transmitters and, in addition, N-type VDCCs, with a higher affinity for GVIA than MVIIC, are required for the release of 5-HT, DA and ACh. The non-N-type VDCC is not the O-type as it is not blocked by low (< 10 nM) concentrations of MVIIC. Further resolution of this VDCC into P or Q-type requires more selective antagonists.
authors.affiliation: Eli Lilly and Company, Lilly Research Centre Ltd., Windlesham, Surrey, UK.
authors.forename: J
authors.initials: J
authors.lastname: Harvey
authors.forename: S
authors.initials: S
authors.lastname: Wedley
authors.forename: J D
authors.initials: JD
authors.lastname: Findlay
authors.forename: M R
authors.initials: MR
authors.lastname: Sidell
authors.forename: I A
authors.initials: IA
authors.lastname: Pullar
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010455:Peptides; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism; D013111:Spider Venoms / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism; D020867:omega-Agatoxin IVA; D020866:omega-Conotoxin GVIA
chemical_list: D002121:Calcium Channel Blockers; D018377:Neurotransmitter Agents; D010455:Peptides; D013111:Spider Venoms; D020867:omega-Agatoxin IVA; D002104:Cadmium; D012701:Serotonin; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D020866:omega-Conotoxin GVIA; D000109:Acetylcholine; D011188:Potassium; D004298:Dopamine