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

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, 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.