BAY K 8644, a 1,4‐Dihydropyridine Ca2+ Channel Activator: Dissociation of Binding and Functional Effects in Brain Synaptosomes

Abstract

K⁺-stimulated ⁴⁵Ca²⁺ uptake into rat brain and guinea pig cerebral cortex synaptosomes was measured at 10 s and 90 s at K⁺ concentrations of 5–75 mM. Net increases in ⁴⁵Ca²⁺ uptake were observed in rat and guinea pig brain synaptosomes. ⁴⁵Ca²⁺ uptake under resting or depolarizing conditions was not increased by the 1,4-dihydropyridine BAY K 8644, which has been shown to activate Ca²⁺ channels in smooth and cardiac muscle. High-affinity [³H]nitrendipine binding in guinea pig synaptosomes (K_D= 1.2 × 10^-10M, B_max= 0.56 pmol mg^-1 protein) was competitively displaced with high affinity (IC₅₀, 2.3 × 10^-9M) by BAY K 8644. Thus high-affinity Ca²⁺ channel antagonist and activator binding sites exist in synaptosome preparations, but their relationship to functional Ca²⁺ channels is not clear.