3,4-Diaminopyridine-evoked norepinephrine release from hippocampal in the absence of extracellular calcium

Slices of rat hippocampus, preincubated with [3H]norepinephrine ([3H]NE), were superfused and stimulated by addition of 3,4-diaminopyridine (3,4-DAP) for 10 min to the superfusion medium. 3,4-DAP-evoked [3H]NE release both in the absence and presence of extracellular Ca2+. 3,4-DAP-evoked Ca(2+)-independent release of [3H]NE was highly sensitive to sodium channel blocker, tetrodotoxin (TTX, 100% inhibition), suggesting that Na+ per se entered into nerve terminals but not depolarization of membrane followed by Ca2+ channel opening is necessary for 3,4-DAP-evoked Ca(2+)-independent release of [3H]NE. Phorbol ester PDB increased by 480% of control and polymyxin B (PMB) decreased 3,4-DAP-evoked [3H]NE release by 94% of control in the absence of extracellular Ca2+ indicating that the alterations of voltage-dependent Ca(2+)-currents into the cells are not involved in the mechanism of the modulation of 3,4-DAP-evoked [3H]NE release by protein kinase C.