Regional distribution of calcium channel ligand (1,4-dihydropyridine) binding sites and ⁴⁵Ca²⁺ uptake processes in rat brain

The binding of nimodipine, a 1,4-dihydropyridine Ca²⁺ channel antagonist, and of Bay K 8644, a Ca²⁺ channel activator, was measured in several regions of rat brain and compared to the distribution of K⁺ depolarization-induced ⁴⁵Ca²⁺ uptake into synaptosomes. The maximum binding densities (B_max) of [³H]nimodipine and [³H]Bay K 8644 were not significantly different one from the other, but differed according to brain region with binding being highest in the olfactory bulb and hippocampus, intermediate in the caudate nucleus and cerebral cortex (various regions), and lowest in the cerebellum [563 to 107 fmol/mg protein (mean)]. The K_D values, [³H]nimodipine = 1.8 × 10^-10M (mean) and [³H]Bay K 8644 = 1.4 × 10^-9 M (mean), did not differ according to region. Depolarizationinduced ⁴⁵Ca²⁺ uptake in synaptosomes occurred as fast (1 sec) and slow (10 sec) components distinguished by their selective occurrence in choline-containing and pre-depolarized preparations respectively. Distribution of the fast component of uptake paralleled that of [³H]nimodipine binding, being least in the cerebellum and greatest in the hippocampus and cortex, but the magnitude of the slow phase of ⁴⁵Ca²⁺ uptake did not vary in the three brain regions studied.