NMDA receptor, protein kinase C and calmodulin system participate in the long-term potentiation in guinea pig superior colliculus slices.

To investigate the involvement of N-methyl-D-aspartate (NMDA) receptor, protein kinase C (PKC) and calmodulin on long-term potentiation (LTP) formation in the superior colliculus (SC), the effects of an NMDA receptor antagonist (D-APV), PKC inhibitors (H-7, K-252a, K-252b, polymyxin B), a protein kinase A (PKA) inhibitor (H-8) and a calcium/calmodulin-dependent kinase inhibitor (calmidazolium) on LTP formation were studied in guinea pig SC slices. APV (100 microM) masked the expression of LTP by tetanic stimulation, but the LTP once formed was not influenced by application of APV. LTP was blocked by application of H-7 (100 microM), but LTP reappeared 20 min after removal of H-7 from the perfusion medium without further tetanic stimulation. On the other hand, established LTP was also inhibited by application of H-7 even 90 min after the tetanic stimulation. Application of K-252a (500 nM) inhibited LTP formation, but K-252b (500 nM) had no inhibitory effect on LTP formation since K-252b, unlike K-252a, cannot permeate the cell membrane. Tetanic stimulation was applied 20 min after application of polymyxin B (1 microM) to the medium but it could not induce LTP, while established LTP was not influenced by the drug. Application of calmidazolium (50 microM) inhibited LTP formation, but had no inhibitory effect on LTP once formed. These results suggest that both the NMDA receptor and calmodulin system are involved in the induction of LTP after tetanic stimulation. This leads to PKC activation which maintains the LTP.