VOLTAGE-ACTIVATED CALCIUM CHANNELS INVOLVED IN VERATRIDINE-EVOKED [H-3]DOPAMINE RELEASE IN RAT STRIATAL SLICES

The present study explored the role of different sub-types of voltage- activated Ca2+ channels (VACCs) in mediating veratridine-evoked [H-3]d opamine (DA) release from rat striatal slices. The release of [H-3]DA evoked by veratridine (25 mu M) decreased by 50.6 +/- 2.9% (n = 8) in the absence of calcium and was completely abolished by 1 mu M tetrodot oxin. The L-type Ca2+ channel blockers nifedipine (10 mu M), nitrendip ine (10 mu M), diltiazem (10 mu M) and verapamil (IO mu M) did not mod ulate this release. Similarly, [H-3]DA release was affected neither by the N-type VACC blocker omega-conotoxin-GVIA (I mu M) nor by the sele ctive P-type channel blockers omega-agatoxin-IVA and omega-agatoxin-TK at low nM concentrations (30 nM), indicating no involvement of N- and P-type Ca2+ channels. In contrast, higher concentrations of w-agatoxi n-IVA that would also inhibit Q-type VACCs, blocked the release of [H- 3]DA by 27.9 +/- 8.1% (n = 5) and 37.5 +/- 13.6% (n = 3) at 0.3 and 1 mu M, respectively. In addition, application of the Q-type Ca2+ channe l blocker omega-conotoxin-MVIIC (0.01-3 mu M) reduced [H-3]DA release in a concentration-dependent manner, with maximum inhibition of 35.3 /- 4.1% at 3 mu M (n = 5). On the basis of these results, it is conclu ded that the Ca2+ channels that participate in veratridine-evoked [3H] DA release are Q-type Ca2+ channels. (C) 1998 Elsevier Science Ltd. Al l rights reserved.