Longo R, Sagratella S, Scotti de Carolis A
Pharmacology Department, Istituto Superiore di Sanità, Roma, Italy.
Life Sci. 1994;55(6):455-62. doi: 10.1016/0024-3205(94)90057-4.
The effects of various calcium antagonists, acting at the different neuronal calcium channels, were studied towards two models of in vitro neuronal injury in rat hippocampal slices. In particular, the influence of the drugs were tested on the electrical failure induced by treatment of hippocampal slices with hypoxia or high concentrations of the excitatory amino acid N-methyl-D-aspartate (NMDA). The L-type calcium antagonists, nifedipine (100 microM) and diltiazem (100 microM) or the T-type calcium antagonist amiloride (100 microM) failed to significantly affect the recovery from the CA1 electrical failure induced by both hypoxia or NMDA (50 microM). The N-type calcium antagonists, omega-conotoxin GVIA (0.5 microM) and neomycin (300 microM) significantly (P < 0.01) increased the probability of the recovery of the CA1 population spike after hypoxia but not after NMDA (50 microM). The glutamate antagonist dizocilipine (50 microM), tested for comparison, significantly (P < 0.01) increased the probability of the recovery of the CA1 population spike after hypoxia and NMDA (50 microM). The results suggest an involvement of calcium channels especially of N-type in the genesis of hypoxic but not NMDA neuronal injury.
研究了作用于不同神经元钙通道的各种钙拮抗剂对大鼠海马切片两种体外神经元损伤模型的影响。具体而言，测试了这些药物对用缺氧或高浓度兴奋性氨基酸N-甲基-D-天冬氨酸（NMDA）处理海马切片所诱导的电衰竭的影响。L型钙拮抗剂硝苯地平（100微摩尔）和地尔硫䓬（100微摩尔）或T型钙拮抗剂阿米洛利（100微摩尔）未能显著影响由缺氧或NMDA（50微摩尔）诱导的CA1电衰竭的恢复。N型钙拮抗剂ω-芋螺毒素GVIA（0.5微摩尔）和新霉素（300微摩尔）显著（P<0.01）增加了缺氧后而非NMDA（50微摩尔）后CA1群体峰恢复的概率。作为对照测试的谷氨酸拮抗剂地佐环平（50微摩尔）显著（P<0.01）增加了缺氧和NMDA（50微摩尔）后CA1群体峰恢复的概率。结果表明钙通道尤其是N型钙通道参与了缺氧性神经元损伤的发生，而不参与NMDA诱导的神经元损伤。
