Studies of [3H]nitrendipine binding and KCl-induced calcium uptake in rat cortical synaptosomes.

Rat cortical synaptosomal fraction was used to study whether there is a direct link between [3H]nitrendipine binding and KCl-induced calcium uptake. [3H]Nitrendipine exhibited reversible and saturable binding to this preparation. The equilibrium dissociation constant Kd was 0.6 nM and the maximal binding capacity, Bmax, was 120 fmol/mg of protein. The binding could be displaced by certain calcium channel antagonists, the potency of which was in the order: nitrendipine greater than nifedipine greater than D600 greater than verapamil greater than flunarizine. Voltage-dependent 45Ca2+-uptake into this fraction was measured after 20 sec KCl-induced depolarization. Nitrendipine at high concentration (10 microM) had little effect on 45Ca2+-uptake into brain synaptosomes. The order of the above-mentioned calcium antagonists affecting 45Ca2+-uptake was flunarizine greater than D600 greater than verapamil greater than nifedipine greater than nitrendipine. Our results suggest that high-affinity binding of [3H]nitrendipine is not directly linked to voltage-dependent calcium uptake in brain.