Kubo T, Yokoi T, Hagiwara Y, Fukumori R, Goshima Y, Misu Y
Department of Pharmacology, Showa Pharmaceutical University, Machida, Tokyo, Japan.
Brain Res Bull. 2001 Mar 1;54(4):413-9. doi: 10.1016/s0361-9230(01)00429-4.
Effects of excitatory amino acid receptor antagonists and voltage-dependent Ca(2+) channel antagonists on ischemia-induced intracellular free Ca(2+) accumulation in rat hippocampal slices were examined. Ischemia caused a large Ca(2+) accumulation in CA1 region but a small Ca(2+) accumulation in CA3 and dentate gyrus regions. When applied during ischemia, the NMDA receptor antagonist MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine maleate) inhibited the ischemic Ca(2+) accumulation only in the CA1, but the non-NMDA receptor antagonist CNQX (6-cyano-7-nitroquinoxaline-2,3-dione) inhibited it in all the three regions. The L-type Ca(2+) channel antagonists nifedipine and verapamil inhibited the ischemic Ca(2+) accumulation only in the CA1 region, but omega-conotoxin, a N- and L-type Ca(2+) channel antagonist inhibited the Ca(2+) accumulation in all the three regions of the hippocampus. When applied after 5-min ischemia, nifedipine but not MK-801, inhibited sustained postiscehmic Ca(2+) elevation in the CA1 region but not in the CA3 and dentate gyrus regions. These findings suggest that the enhanced ischemia-induced Ca(2+) accumulation in the CA1 region is mediated via activation of both NMDA receptors and L-type-like Ca(2+) channels. It appears that sustained postischemic Ca(2+) elevation in the CA1 region is mediated via activation of L-type-like Ca(2+) channels, but not of NMDA receptors.
研究了兴奋性氨基酸受体拮抗剂和电压依赖性Ca(2+)通道拮抗剂对大鼠海马切片缺血诱导的细胞内游离Ca(2+)蓄积的影响。缺血导致CA1区大量Ca(2+)蓄积，但CA3区和齿状回区Ca(2+)蓄积较少。在缺血期间应用时，NMDA受体拮抗剂MK-801（(+)-5-甲基-10,11-二氢-5H-二苯并[a,d]环庚烯-5,10-亚胺马来酸盐）仅抑制CA1区的缺血性Ca(2+)蓄积，但非NMDA受体拮抗剂CNQX（6-氰基-7-硝基喹喔啉-2,3-二酮）在所有三个区域均抑制其蓄积。L型Ca(2+)通道拮抗剂硝苯地平和维拉帕米仅抑制CA1区的缺血性Ca(2+)蓄积，但ω-芋螺毒素（一种N型和L型Ca(2+)通道拮抗剂）抑制海马所有三个区域的Ca(2+)蓄积。在缺血5分钟后应用时，硝苯地平而非MK-801抑制CA1区但不抑制CA3区和齿状回区的缺血后持续性Ca(2+)升高。这些发现表明，CA1区缺血诱导的Ca(2+)蓄积增强是通过NMDA受体和L型样Ca(2+)通道的激活介导的。似乎CA1区缺血后持续性Ca(2+)升高是通过L型样Ca(2+)通道的激活介导的，而非NMDA受体的激活。
