Inhibition of postsynaptic PKC or CaMKII blocks induction but not expression of LTP.
Long-term potentiation (LTP) of synaptic transmission is a widely studied cellular example of synaptic plasticity. However, the identity, localization, and interplay among the biochemical signals underlying LTP remain unclear. Intracellular microelectrodes have been used to record synaptic potentials and deliver protein kinase inhibitors to postsynaptic CA1 pyramidal cells. Induction of LTP is blocked by intracellular delivery of H-7, a general protein kinase inhibitor, or PKC(19-31), a selective protein kinase C (PKC) inhibitor, or CaMKII(273-302), a selective inhibitor of the multifunctional Ca2+-calmodulin-dependent protein kinase (CaMKII). After its establishment, LTP appears unresponsive to postsynaptic H-7, although it remains sensitive to externally applied H-7. Thus both postsynaptic PKC and CaMKII are required for the induction of LTP and a presynaptic protein kinase appears to be necessary for the expression of LTP.
Malinow
R
R
Department of Molecular and Cellular Physiology, Beckman Center, Stanford University School of Medicine 94305.
Schulman
H
H
Tsien
R W
RW
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000502:physiology*; D051381:Rats; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D017981:Receptors, Neurotransmitter / Q000502:physiology; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D007546:Isoquinolines; D010879:Piperazines; D011493:Protein Kinase C; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D017981:Receptors, Neurotransmitter