Effect of Ca²⁺ Antagonists on High-K⁺ Evoked Increase in [Ca²⁺]_i in Rat Cerebral Synaptosomes and Hippocampal Neurons

Abstract

By fura-2 fluorometry, we investigated the direct effects of Ca²⁺ antagonists including a new benzothiazepine, clentiazem, on the high-K⁺-evoked increase in the concentration of cytosolic free Ca²⁺ ([Ca²⁺]_i) in rat cerebral synaptosomes and cultured hippocampal neurons. In both preparations, metal ions inhibited the high-K⁺-induced increase in [Ca²⁺]_i, in the following order: La³⁺ > Cd²⁺ >> Ni². Although flunarizine and nicardipine inhibited the K⁺-induced increase in [Ca²⁺]_i in synaptosomes, other Ca²⁺ antagonists, including clentiazem and nitrendipine, had little effect at 10 μM. In hippocampal neurons, clentiazem inhibited the K⁺-induced increase in [Ca²⁺]_i at 10 μM, as did flunarizine and nicardipine. However, nifedipine and nitrendipine had little effect in either cultured neurons or in synaptosomes.