Protein kinase C activity is not responsible for the expression of long-term potentiation in hippocampus.
Long-term potentiation (LTP) in hippocampus has been proposed to result from a tonic activation of protein kinase C. This hypothesis predicts that stimulation of the kinase would produce a smaller change in response size on potentiated versus control pathways and, conversely, that inhibition of the kinase would reduce potentiated inputs to a greater degree than control responses. We tested these predictions using phorbol esters to activate and using the antagonist H-7 to inhibit protein kinase C; we found that the actions of these drugs on synaptic transmission were not affected by prior induction of LTP. Both compounds, however, significantly decreased the contribution of N-methyl-D-aspartate receptors to synaptic potentials, a result that accounts for the suppressive effects of these compounds on LTP formation. Thus protein kinase C is probably not involved in the expression of LTP but may play a role in the receptor-mediated events participating in its induction.
Muller
D
D
Department of Pharmacology, Centre Medical Universitaire, Geneva, Switzerland.
Buchs
P A
PA
Dunant
Y
Y
Lynch
G
G
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D006624:Hippocampus / Q000201:enzymology*; D007546:Isoquinolines / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009473:Neuronal Plasticity / Q000502:physiology*; D010703:Phorbol Esters / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
D007546:Isoquinolines; D010703:Phorbol Esters; D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C