45Ca2+ Uptake into Rat Whole Brain Synaptosomes Unaltered by Dihydropyridine Calcium Antagonists

Abstract

Voltage-dependent ⁴⁵Ca²⁺ uptake into rat whole brain synaptosomes was measured after 3-s KClinduced depolarization to investigate possible inhibitory effects of calcium antagonists, nitrendipine, nimodipine, and nisoldipine. At a Ca²⁺ concentration of 1.2 mM, nitrendipine, in concentrations ranging from 0.1 nM to 10 μM, had no effect on ⁴⁵Ca²⁺ uptake. When the Ca²⁺ concentration was lowered to 0.06 and 0.12 μM, nitrendipine, 10 μM, inhibited ⁴⁵Ca²⁺ uptake in response to 109 mM KC1 depolarization. However, in a separate concentration response study, nitrendipine, nimodipine, and nisoldipine, 0.1 μM to 10 μM, failed to alter the uptake of ⁴⁵Ca²⁺ (0.06 mM Ca²⁺) into 30 mM KCl-depolarized synaptosomes. The high concentrations of these agents required to depress ⁴⁵Ca²⁺ uptake indicate that the dihydropyridine calcium antagonists are considerably less potent in brain tissue than in peripheral tissue.