Presynaptic role of cGMP-dependent protein kinase during long-lasting potentiation.
Previous research has suggested that cGMP-dependent protein kinases (cGKs) may play a role in long-term potentiation in hippocampus, but their site of action has been unknown. We examined this question at synapses between pairs of hippocampal neurons in dissociated cell culture. Injection of a specific peptide inhibitor of cGK into the presynaptic but not the postsynaptic neuron blocked long-lasting potentiation induced by tetanic stimulation of the presynaptic neuron. As controls, injection of a scrambled peptide or a peptide inhibitor of cAMP-dependent protein kinase into either neuron did not block potentiation. Conversely, injection of the alpha isozyme of cGK type I into the presynaptic but not the postsynaptic neuron produced activity-dependent potentiation that did not require NMDA receptor activation. Evidence from Western blots, reverse transcription-PCR, activity assays, and immunocytochemistry indicates that endogenous cGK type I is present in the neurons, including presynaptic terminals. These results support the idea that cGK plays an important presynaptic role during the induction of long-lasting potentiation in hippocampal neurons.
Arancio
O
O
Center for Neurobiology and Behavior, Columbia University, New York, New York 10032, USA.
Antonova
I
I
Gambaryan
S
S
Lohmann
S M
SM
Wood
J S
JS
Lawrence
D S
DS
Hawkins
R D
RD
D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism / Q000506:poisoning; D015153:Blotting, Western; D002478:Cells, Cultured; D017869:Cyclic GMP-Dependent Protein Kinases / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000378:metabolism; D017774:Long-Term Potentiation / Q000502:physiology*; D008845:Microinjections; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000943:Antigens, Differentiation; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D007527:Isoenzymes; D017869:Cyclic GMP-Dependent Protein Kinases