EFFECTS OF DIHYDROPYRIDINE CALCIUM-ANTAGONISTS ON RAT MIDBRAIN DOPAMINERGIC-NEURONS

1 The effects of the dihydropyridine calcium channel antagonists, nife dipine and nimodipine (300 nM-30 mu M) were tested in vitro on intrace llularly recorded dopaminergic neurones in the rat ventral mesencephal on. 2 Bath applied nifedipine and nimodipine inhibited in a concentrat ion-dependent manner the spontaneous firing discharge of the action po tentials, whereas, the dihydropyridine calcium channel agonist, Bay K 8644 increased the firing rate. 3 Pacemaker oscillations and bursts of action potentials were produced by loading the cells with caesium. Ni fedipine and nimodipine reduced the rate and the duration of the caesi um-induced membrane oscillations and decreased the number of action po tentials in a burst. During the blockade of potassium currents the dop aminergic neurones often developed a prolonged (100-800 ms) afterdepol arization that was also inhibited by dihydropyridines. 4 The spontaneo us discharge of calcium spikes was also inhibited by both dihydropyrid ine calcium antagonists. The apparent input resistance and the level o f membrane potential were not affected by the dihydropyridine calcium antagonists. 5 If the action potential duration was less than 150 ms t he shape of the spike was not clearly influenced by both calcium antag onists. However, when the duration of the action potential was longer than 150-200 ms due to the intracellular injection of caesium ions plu s the extracellular application of tetraethylammonium (10-50 mM), both nifedipine and nimodipine reversibly shortened the plateau potential. 6 It is suggested that nifedipine and nimodipine depress the rhythmic and bursting activity of the dopaminergic cells and shorten the calci um action potential by blocking dihydropyridine-sensitive high-thresho ld calcium currents.