Differential Effects of Potassium Channel Blockers on Dopamine Release from Rat Striatal Slices

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