Presynaptic Role of cGMP-Dependent Protein Kinase during Long-Lasting Potentiation

• Published in: The Journal of neuroscience 2001-01, Vol.21 (1), p.143-149
• Main Authors: Arancio, Ottavio, Antonova, Irina, Gambaryan, Stepan, Lohmann, Suzanne M, Wood, Jason S, Lawrence, David S, Hawkins, Robert D
• Format: Article
• Language: English
• Subjects: Animals; Antigens, Differentiation - metabolism; Antigens, Differentiation - poisoning; Blotting, Western; Cells, Cultured; Cyclic GMP-Dependent Protein Kinases - administration & dosage; Cyclic GMP-Dependent Protein Kinases - antagonists & inhibitors; Cyclic GMP-Dependent Protein Kinases - metabolism; Electric Stimulation; Enzyme Inhibitors - pharmacology; Excitatory Amino Acid Antagonists - pharmacology; Excitatory Postsynaptic Potentials - physiology; Hippocampus - cytology; Hippocampus - drug effects; Hippocampus - enzymology; Immunohistochemistry; Isoenzymes - administration & dosage; Isoenzymes - antagonists & inhibitors; Isoenzymes - metabolism; Long-Term Potentiation - physiology; Microinjections; Neurons - cytology; Neurons - drug effects; Neurons - enzymology; Patch-Clamp Techniques; Presynaptic Terminals - drug effects; Presynaptic Terminals - enzymology; Rats; Rats, Sprague-Dawley
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/JNEUROSCI.21-01-00143.2001

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.