Development of hippocampal long-term potentiation is reduced by recently introduced calpain inhibitors.

The effects of two recently synthesized inhibitors of calpains, calpain inhibitor I (CiI) and calpain inhibitor II (CiII) were tested on the development of long-term potentiation (LTP) in region CA1 of rat hippocampus. Slices maintained in 100 microM of CiI or CiII showed an initial degree of potentiation after theta burst stimulation that, in contrast to controls, slowly decayed across time. The effects of CiI and CiII appeared to be independent of possible actions on the physiological mechanisms that take place during the induction stage of LTP. Since these inhibitors are more potent and specific than leupeptin in blocking calpain activity, their effects on LTP can be more convincingly ascribed to a selective blockade of the calcium-sensitive protease. Accordingly, the results favor the idea that a proteolytic event of the kind found after N-methyl-D-aspartate receptor activation is an intermediary step in the development of LTP.