DIFFERENTIAL-EFFECTS OF POTASSIUM CHANNEL BLOCKERS ON DOPAMINE RELEASE FROM RAT STRIATAL SLICES

The effects of different potassium channel blockers on tritiated dopamine ([H-3]DA) release were investigated in rat striatal slices in the presence of pargyline and nomifensine (10-mu-M each). 4-Aminopyridine (4-AP; 10 and 30-mu-M) and 3,4-diaminopyridine (3,4-DAP; 30-mu-M) markedly increased the basal tritium outflow, whereas tetraethylammonium (TEA; 100-1000-mu-M) was without effect. The facilitating effect of 4-AP (10-mu-M) on spontaneous release was Ca2+- and K+-dependent. Moreover, the 4-AP-induced increase in spontaneous release was abolished in the presence of tetrodotoxin, indicating that voltage-dependent Na+ channels were involved in the release mechanism. 4-AP (10 and 30-mu-M) induced a dose-dependent decrease in K+-evoked [H-3]DA release. This effect was confirmed with 3,4-DAP (30-mu-M). When striatal slices were depolarized with veratridine (5-mu-M), these two aminopyridines increased the evoked release of [H-3]DA. TEA increased both K+- and veratridine-evoked [H-3]DA release. These biochemical results are consistent with electrophysiological differences between the mechanism of action of aminopyridines and that of TEA.