ω-Agatoxin IVA identifies a single calcium channel subtype which contributes to the potassium-induced release of acetylcholine, 5-hydroxytryptamine, dopamine, γ-aminobutyric acid and glutamate from rat brain slices

• Published in: Neuropharmacology 1996-04, Vol.35 (4), p.385-392
• Main Authors: Harvey, Janette, Wedley, Susan, Findlay, Jeremy D., Sidell, Mark R., Pullar, Ian A.
• Format: Article
• Language: English
• Subjects: Acetylcholine - metabolism; Animals; Biological and medical sciences; Cadmium - pharmacology; Calcium Channel Blockers - pharmacology; Calcium channels; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Dopamine - metabolism; Fundamental and applied biological sciences. Psychology; gamma-Aminobutyric Acid - metabolism; Glutamic Acid - metabolism; In Vitro Techniques; Male; Neurotransmitter Agents - metabolism; neurotransmitter release; omega-Agatoxin IVA; omega-Conotoxin GVIA; Peptides; Potassium - pharmacology; Rats; Rats, Inbred Strains; Serotonin - metabolism; Spider Venoms - pharmacology; Vertebrates: nervous system and sense organs; ω-agatoxin IVA; ω-conotoxin GVIA; ω-conotoxin MVIIC
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/0028-3908(96)00010-X

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, ω-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, ω-agatoxin IVA (Aga IVA, 1 μM), blocked 100% of GABA and glutamate, 70% of DA and about 50% of 5-HT and ACh release. The slopes of the inhibition curves indicate that it acts on the same, single type of VDCC in all cases. ω-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.