Postsynaptic injection of CA2+/CaM induces synaptic potentiation requiring CaMKII and PKC activity.
CA2+-regulated protein kinases play critical roles in long-term potentiation (LTP). To understand the role of Ca2+/calmodulin (CaM) signaling pathways in synaptic transmission better, Ca2+/CaM was injected into hippocampal CA1 neurons. Ca2+/CaM induced significant potentiation of excitatory synaptic responses, which was blocked by coinjection of a CaM-binding peptide and was not induced by injections of Ca2+ or CaM alone. Reciprocal experiments demonstrated that Ca2+/CaM-induced synaptic potentiation and tetanus-induced LTP occluded one another. Pseudosubstrate inhibitors or high-affinity substrates of CaMKII or PKC blocked Ca2/CaM-induced potentiation, indicating the requirement of CaMKII and PKC activities in synaptic potentiation. We suggest that postsynaptic levels of free Ca2+/CaM is a rate limiting factor and that functional cross-talk between Ca2+/CaM and PKC pathways occurs during the induction of LTP.
Wang
J H
JH
Department of Neurobiology and Anatomy, University of Texas, Houston 77225, USA.
Kelly
P T
PT
D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000502:physiology*; D002147:Calmodulin / Q000494:pharmacology*; D002148:Calmodulin-Binding Proteins / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D004558:Electric Stimulation; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000494:pharmacology; D051579:Neurogranin; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000494:pharmacology / Q000502:physiology*; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D002147:Calmodulin; D002148:Calmodulin-Binding Proteins; D009419:Nerve Tissue Proteins; C496651:Nrgn protein, rat; D010446:Peptide Fragments; D051579:Neurogranin; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002118:Calcium