Effects of Ca2+ antagonists on 45Ca2+ uptake by rat whole brain P1 and P2 fractions

Voltage-dependent 45Ca2+ uptake into rat whole brain P1 (nonsynaptosomal) and P2 (synaptosomal) fractions was measured after 60-s KCl-stimulated depolarization to investigate possible inhibitory effects of Ca2+ antagonists, nitrendipine, diltiazem, verapamil and ifenprodil tartrate. All drugs (10(-5)M) had little influence on 45Ca2+ uptake by whole brain P1 fraction in both nondepolarizing and depolarizing mediums. Diltiazem (10(-5)M) had no influence on 45Ca2+ uptake by whole brain P2 fraction under both conditions. However, nitrendipine (10(-5)M) verapamil (10(-5)M) and ifenprodil tartrate inhibited depolarization-dependent 45Ca2+ uptake by whole brain P2 fraction, while nondepolarization-dependent 45Ca2+ uptake was not affected by these drugs. The inhibitory sequence of depolarization-dependent 45Ca2+ uptake by P2 fraction was: ifenprodil tartrate greater than nitrendipine greater than verapamil. These results suggest that ifenprodil tartrate, nitrendipine and verapamil specifically inhibit depolarization-dependent synaptosomal 45Ca2+ uptake, but that diltiazem has little influence on it.