Participation of intracellular sites in the action of Ca2+ channel blockers.

The action of phenylalkylamine Ca2+ channel blockers D890 and D888 on Ca2+ uptake and neurotransmitter amino acid release were studied. D890, the quaternary derivative of D600, did not inhibit veratrine-induced 45Ca2+ uptake or the release of neurotransmitter amino acids from rat cerebrocortical synaptosomes, except at high concentrations (200 microM) when it was probably acting extracellularly in a non-specific manner. This contrasted with the more potent (10-50 microM) inhibitory actions of D600 and D888, and may be due to the inability of D890 to cross the synaptic plasma membrane. (-)D888 was shown to cross cell membranes and accumulate in the intracellular compartment of cerebrocortical slices and synaptosomes, where it was associated predominantly with the soluble cytoplasmic fraction.