Activation of pre- and postsynaptic protein kinase C during tetraethylammonium-induced long-term potentiation in the CA1 field of the hippocampus.
Tetraethylammonium (TEA) induces a form of long-term potentiation (LTP) that is independent on N-methyl-D-aspartate (NMDA) receptor activation (LTP(K)). LTP(K) may be a suitable chemical model to study molecular mechanisms underlying LTP. We monitored the phosphorylation state of two identified neural-specific protein kinase C (PKC) substrates (the presynaptic protein GAP-43/B-50 and postsynaptic protein RC3) after different chemical depolarisations. TEA induced a long-lasting increase in synaptic efficacy in the CA1 field of the hippocampus and increased the phosphorylation of both GAP-43/B-50 and RC3 (51 and 56.1%, respectively). These effects were blocked by the voltage-dependent calcium channel antagonist nifedipine, but not by the NMDA receptor antagonist AP5. These data show that in LTP(K) the in situ phosphorylation of pre-and postsynaptic PKC substrates is increased, indicating that NMDA receptor-dependent and NMDA receptor-independent LTP share common Ca(2+)-dependent expression mechanisms, including activation of pre- and postsynaptic PKC.
Ramakers
G M
GM
Rudolf Magnus Institute for Neurosciences, Department of Medical Pharmacology, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands. g.m.j.ramakers@med.uu.nl
Pasinelli
P
P
van Beest
M
M
van der Slot
A
A
Gispen
W H
WH
De Graan
P N
PN
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002148:Calmodulin-Binding Proteins / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D019922:GAP-43 Protein / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D051579:Neurogranin; D009543:Nifedipine / Q000494:pharmacology; D010766:Phosphorylation; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure; D011493:Protein Kinase C / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013570:Synaptic Membranes / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D019789:Tetraethylammonium / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D002148:Calmodulin-Binding Proteins; D018691:Excitatory Amino Acid Antagonists; D019922:GAP-43 Protein; D009419:Nerve Tissue Proteins; C496651:Nrgn protein, rat; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D051579:Neurogranin; D019789:Tetraethylammonium; D015763:2-Amino-5-phosphonovalerate; D015761:4-Aminopyridine; D011493:Protein Kinase C; D009543:Nifedipine