Effect of Ca2+ Antagonists on High-K+ Evoked Increase in (Ca2+)i in Rat Cerebral Synaptosomes and Hippocampal Neurons.

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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.
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