In contrast, the delayed type response was pre-vented by removal and chelation of extracellular Ca 2+ . Moreover, although the number of cells exhibiting an immediate response to treatment with the O4 monoclonal IgM was not affected by blocking several classes of plasma membrane Ca 2+ channels, pharmacologically blocking the activity of phospholipase C (PLC) significantly decreased the percentage of astrocytes that exhibited elevated intracellular Ca 2+ . In contrast, the delayed Ca 2+ response in oligodendrocytes was not dependent on intracellular stores, but was sensitive to pharmacological inhibition of Ca 2+ flux through α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-sensitive glutamate channels . These data support the conclusion that the delayed response in oligodendrocytes is dependent on Ca 2+ entry through AMPA receptor Ca 2+ channels, whereas the immediate response in astrocytes is dependent on Ca 2+ release from endoplasmic reticulum stores, likely through PLC-mediated generation of IP 3 and gating of IP 3sensitive calcium channels.