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 types of voltage-sensitive calcium channels for depolarisation-induced release of endogenous dopamine from dendrites and cell bodies in superfused guinea pig substantia nigra slices was investigated. The stimulatory effect of veratridine (10 microM) on dopamine release was only marginally attenuated in Ca(2+)-free medium but was completely blocked by tetrodotoxin (1 microM) and by the dopamine reuptake inhibitor GBR 12909 (10 microM). Low extracellular concentration of Na+ stimulated the dopamine release. Potassium-evoked dopamine release was completely Ca(2+)-dependent, not blocked by GBR 12909 and partially blocked by tetrodotoxin. Nifedipine (20 microM), omega-conotoxin GVIA (0.5 microM), penfluridol (5 microM), and Ni2+ (20 microM) had no effect, amiloride (1 mM) attenuated and neomycin (350 microM), and omega-agatoxin IVA (1 microM) almost totally blocked the potassium-induced dopamine release. The results suggest that veratridine released dopamine mostly by reversing the dopamine transporter. High concentrations of potassium induced release of nigral dopamine 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 calcium channels both by the depolarisation induced by potassium per se and by the secondary depolarisation induced by opening of voltage-dependent sodium channels.
Elverfors
A
A
Department of Pharmacology, Göteborg University, Sweden.
Jonason
J
J
Jonason
G
G
Nissbrandt
H
H
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D010477:Perfusion; D011188:Potassium / Q000037:antagonists & inhibitors / Q000494:pharmacology; D012964:Sodium / Q000502:physiology; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism*; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology; D014701:Veratridine / Q000037:antagonists & inhibitors / Q000494:pharmacology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D018765:Dopamine Uptake Inhibitors; D015222:Sodium Channels; D013779:Tetrodotoxin; D014701:Veratridine; D012964:Sodium; D011188:Potassium; D004298:Dopamine