Modulation of potassium-evoked [3H]dopamine release from rat striatal slices by voltage-activated calcium channel ligands: effects of omega-conotoxin-MVIIC.
We examined the involvement of voltage-activated Ca2+ channels (VACCs) on K+(50 mM)-evoked [3H]dopamine ([3H]DA) release from superfused rat striatal slices. Neither nifedipine nor nitrendipine modified K(+)-evoked [3H]DA release, indicating that L-type VACCs are not involved. K(+)-evoked [3H]DA release was partially inhibited by omega-CTx-GVIA and omega-Aga-IVA, and was abolished by 3 microM omega-CTx-MVIIC (IC50 approximately 128 nM), suggesting the involvement of N-, P-, or Q-type VACCs, respectively. Moreover, even subnanomolar concentrations of omega-CTx-MVIIC (0.1-0.5 nM) inhibited K(+)-evoked [3H]DA release by approximately 25%, suggesting the possible involvement of a still not classified (perhaps O-type?) Ca2+ channel subtype. The effects of omega-CTx-MVIIC (10-100 nM) and omega-CTx-GVIA (1 microM) were additive, suggesting that low nanomolar concentrations of omega-CTx-MVIIC does not interact with N-type VACCs. In conclusion, the K(+)-evoked [3H]DA release from rat striatal slices is mediated by entry of Ca2+ through omega-CTx-GVIA sensitive (N-type) as well as through omega-Aga-IVA (P-type) and omega-CTx-MVIIC (probably Q-type) sensitive VACCs.
Dobrev
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Institute of Pharmacology and Toxicology, Faculty of Medicine, University of Technology, Dresden, Germany.
Andreas
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D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D066298:In Vitro Techniques; D008024:Ligands; D008297:Male; D008978:Mollusk Venoms / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013111:Spider Venoms / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014316:Tritium; D020867:omega-Agatoxin IVA; D020866:omega-Conotoxin GVIA; D020960:omega-Conotoxins
D002121:Calcium Channel Blockers; D008024:Ligands; D008978:Mollusk Venoms; D010455:Peptides; D013111:Spider Venoms; D020867:omega-Agatoxin IVA; D020960:omega-Conotoxins; D014316:Tritium; C075851:omega-conotoxin-MVIIC; D013779:Tetrodotoxin; D020866:omega-Conotoxin GVIA; D011188:Potassium; D004298:Dopamine