Autonomously active protein kinase C in the maintenance phase of N-methyl-D-aspartate receptor-independent long term potentiation.
In area CA1 of the hippocampus, the induction of long term potentiation (LTP) requires activation of either N-methyl-D-aspartate receptors (NMDA receptor-dependent LTP) or voltage-gated Ca2+ channels (NMDA receptor-independent LTP). We have investigated biochemical sequelae of NMDA receptor-independent LTP induction. We find that a persistent increase in second messenger-independent protein kinase C activity is associated with the maintenance phase of NMDA receptor-independent LTP. This increase in protein kinase C activity is prevented by blocking LTP with nifedipine, a Ca2+ channel antagonist, or kynurenic acid, a nonselective glutamate receptor antagonist. Additionally, we find an increase in the catalytic fragment of protein kinase C (PKM) in the maintenance phase of NMDA receptor-independent LTP, indicating that proteolytic activation of protein kinase C may account for its autonomous activation. This increase in the catalytic fragment of protein kinase C is also prevented by blocking LTP induction. These results are the first to demonstrate that persistent protein kinase C activation is a possible mechanism for the maintenance of NMDA receptor-independent LTP.
Division of Neuroscience, Baylor College of Medicine, Houston, Texas 77030.
C M
CM
Powell
D
D
Johnston
J D
JD
Sweatt
D000818:Animals; D004789:Enzyme Activation; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D007700:Kinetics; D007736:Kynurenic Acid / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D011712:Pyramidal Tracts / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*; D015290:Second Messenger Systems; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology*; D013997:Time Factors
D016194:Receptors, N-Methyl-D-Aspartate; D013757:Tetraethylammonium Compounds; D019789:Tetraethylammonium; D011493:Protein Kinase C; D007736:Kynurenic Acid; D009543:Nifedipine