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+ greater than Cd2+ much greater than 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 microM. In hippocampal neurons, clentiazem inhibited the K(+)-induced increase in [Ca2+]i at 10 microM, as did flunarizine and nicardipine. However, nifedipine and nitrendipine had little effect in either cultured neurons or in synaptosomes.
Kobayashi
T
T
Biological Research Laboratory, Tanabe Seiyaku Co., Ltd., Saitama, Japan.
Yamauchi
R
R
Murata
S
S
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D002118:Calcium / Q000032:analysis*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D006624:Hippocampus / Q000737:chemistry*; D066298:In Vitro Techniques; D008297:Male; D008670:Metals / Q000494:pharmacology; D009474:Neurons / Q000737:chemistry; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013574:Synaptosomes / Q000737:chemistry*
D002121:Calcium Channel Blockers; D008670:Metals; D011188:Potassium; D002118:Calcium