A novel Na+/Ca2+ channel blocker NS-7 inhibits evoked but not spontaneous dopamine release from rat striatum, as measured by intracerebral microdialysis

The spontaneous dopamine release from rat striatum, measured by intracerebral microdialysis, was markedly reduced by local perfusion of tetrodotoxin (1 mu M) through the dialysis probe. In addition, striatal microinjection of omega-conotoxin GVIA (10 pmol) or omega-agatoxin IVA (1 pmol), but not local perfusion of nimodipine, suppressed the spontaneous dopamine release. Therefore, the spontaneous dopamine release may depend on the activity of both Na+ channel as well as N-type and P/Q-type Ca2+ channels. In contrast, local perfusion of a novel Na+- and Ca2+-channel blocker NS-7 (10 mu M) did not affect spontaneous dopamine release, whereas it markedly blocked KCl- and veratridine-evoked dopamine release. Therefore, NS-7 may block Na+- and Ca2+-channels only when the ion channels are highly activated. (C) 1998 Elsevier Science Ireland Ltd, All rights reserved.