EFFECTS OF DRUGS INTERFERING WITH SODIUM-CHANNELS AND CALCIUM CHANNELS ON THE RELEASE OF ENDOGENOUS DOPAMINE FROM SUPERFUSED SUBSTANTIA-NIGRA SLICES

The importance of voltage-dependent sodium channels and different type s of voltage-sensitive calcium channels for depolarisation-induced rel ease of endogenous dopamine from dendrites and cell bodies in superfus ed guinea pig substantia nigra slices was investigated. The stimulator y effect of veratridine (10 mu M) on dopamine release was only margina lly attenuated in Ca2+-free medium but was completely blocked by tetro dotoxin (1 mu M) and by the dopamine reuptake inhibitor GBR 12909 (10 mu M). Low extracellular concentration of Na+ stimulated the dopamine release. Potassium-evoked dopamine release was completely Ca2+-depende nt, not blocked by GBR 12909 and partially blocked by tetrodotoxin. Ni fedipine (20 mu M), omega-conotoxin GVIA (0.5 mu M), penfluridol (5 mu M), and Ni2+ (20 mu M) had no effect, amiloride (1 mM) attenuated and neomycin (350 mu M), and omega-agatoxin IVA (1 mu M) almost totally b locked the potassium-induced dopamine release. The results suggest tha t veratridine released dopamine mostly by reversing the dopamine trans porter. High concentrations of potassium induced release of nigral dop amine by opening of voltage-sensitive calcium channels of P/Q type but not L-type, N-type and probably not T-type. The depolarisation evoked by high concentrations of potassium seems to open voltage-sensitive c alcium channels both by the depolarisation induced by potassium per se and by the secondary depolarisation induced by opening of voltage-dep endent sodium channels. (C) 1997 Wiley-Liss, Inc.