Selective degeneration of CA1 pyramidal cells by chronic application of bismuth.

The heavy metal bismuth induces a new type of selective neuronal degeneration that shares some common aspects with that seen following hypoxia and ischemia. Continuous application of 3 microns bismuth to organotypic cultures of rat hippocampus resulted after 2-3 weeks in selective degeneration of CA1 pyramidal cells, while CA3 pyramidal cells, dentate granule cells, and subicular neurons were resistant. With 10 microns bismuth, the majority of hippocampal neurons degenerated. The addition of 20 microns MK-801, a noncompetitive NMDA-antagonist, during the entire culturing period failed to prevent neuronal degeneration induced by 3 microns bismuth. GABA-immunoreactive interneurons were also affected by bismuth, but were generally less sensitive than CA1 pyramidal cells. Acute application of up to 100 microns bismuth did not change the electrophysiological properties of CA1 pyramidal cells.