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

The voltage-dependent calcium channels (VDCCs) involved in K+-induced transmitter release have been studied. A maximally effective concentra tion 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 GAB A or glutamate. The O, P and Q-type VDCC inhibitor, omega-agatoxin IVA (Aga IVA, 1 mu M), 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. omega-Conotoxin MVIIC (MVIIC) completely inhibited the release of ail 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 M VIIC, 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) concentra tions of MVIIC. Further resolution of this VDCC into P or Q-type requi res more selective antagonists. (C) 1996 Elsevier Science Ltd.