Effect Of Ca2+ Antagonists On High-K+ Evoked Increase In [Ca2+]I In Rat Cerebral Synaptosomes And Hippocampal-Neurons

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-mu-M. In hippocampal neurons, clentiazem inhibited the K+-induced increase in [Ca2+]i at 10-mu-M, as did flunarizine and nicardipine. However, nifedipine and nitrendipine had little effect in either cultured neurons or in synaptosomes.