Calmodulin in ischemic neurotoxicity of rat hippocampus in vitro

To determine whether calmodulin plays a role in neurodegeneration after ischemia, effects of the selective calmodulin inhibitors calmidazolium and W7 were studied in organotypic cultures of rat hippocampus. Protection of pyramidal cells in the CA1 region of the hippocampus by calmidazolium and W7 against hypoxia/hypoglycemia suggests that activation of intracellular calmodulin plays a significant role in ischemic neuronal injury. Both ryanodine and TMB-8, inhibitors of intracellular Ca²⁺ release, failed to prevent ischemic neuronal injury. These results indicate that calmodulin, a major intracellular Ca²⁺ binding protein, plays a significant role in experimental ischemia-induced hippocampal neuronal injury in vitro.