Increased synthesis of two polypeptides in area CA1 of the hippocampus in response to repetitive electrical stimulation.

Changes in the pattern of newly synthesized polypeptides were investigated in the in vitro hippocampal slice following exposure to repetitive stimulation with and without the induction of long-term potentiation. Using [35S]methionine labeling of polypeptides and two-dimensional gel electrophoresis, we detected an increase in the rate of synthesis of two polypeptides (48 kDa and 89 kDa) in CA1 in response to repetitive stimulation of the Schaffer collaterals. The synthesis of the 48 kDa polypeptide (pI approximately 6.6) increased 240% in response to high-frequency stimulation (100 Hz) relative to the same protein from unstimulated slices (n = 14), and increased 220% in response to low-frequency stimulation (1 Hz) (n = 5). Blockade of the N-methyl-D-aspartate (NMDA) receptor induced the protein 180%, with no further increase following tetanic stimulation. An 89 kDa doublet (pI approximately 6.8) increased 150% following high-frequency and 140% following low-frequency stimulation. Blockade of the NMDA receptor increased this protein as well (180% of the unstimulated control) and no further increase was observed following high-frequency stimulation. Based on physicochemical and electrophysiological properties, these proteins are not identifiable as any of those previously associated with long-term potentiation or repetitive electrical stimulation.