Nitric oxide acts as a postsynaptic signaling molecule in calcium/calmodulin-induced synaptic potentiation in hippocampal CA1 pyramidal neurons.

Postsynaptic injection of Ca(2+)/calmodulin (Ca(2+)/CaM) into hippocampal CA1 pyramidal neurons induces synaptic potentiation, which can occlude tetanus-induced potentiation (Wang and Kelly, 1995). Because Ca(2+)/CaM activates the major forms of nitric oxide synthase (NOS) to produce nitric oxide (NO), NO may play a role during Ca(2+)/CaM-induced potentiation. Here we show that extracellular application of the NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) or postsynaptic co-injection of L-NAME with Ca(2+)/CaM blocked Ca(2+)/CaM-induced synaptic potentiation. Thus, NO is necessary for Ca(2+)/CaM-induced synaptic potentiation. In contrast, extracellular perfusion of membrane-impermeable NO scavengers N-methyl-D-glucamine dithiocarbamate/ferrous sulfate mixture (MGD-Fe) or 2-(4-carboxyphenyl)-4,4,5, 5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO) did not attenuate Ca(2+)/CaM-induced synaptic potentiation, even though MGD-Fe or carboxy-PTIO blocked tetanus-induced synaptic potentiation. This result indicates that NO is not a retrograde messenger in Ca(2+)/CaM-induced synaptic potentiation. However, postsynaptic co-injection of carboxy-PTIO with Ca(2+)/CaM blocked Ca(2+)/CaM-induced potentiation. Postsynaptic injection of carboxy-PTIO alone blocked tetanus-induced synaptic potentiation without affecting basal synaptic transmission. Our results suggest that NO works as a postsynaptic (intracellular) messenger during Ca(2+)/CaM-induced synaptic potentiation.
AuthorsG Y Ko, P T Kelly
JournalThe Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci) Vol. 19 Issue 16 Pg. 6784-94 (Aug 15 1999) ISSN: 1529-2401 [Electronic] UNITED STATES
PMID10436036 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Calmodulin
  • Enzyme Inhibitors
  • Nitric Oxide
  • Nitric Oxide Synthase
  • Calcium
  • NG-Nitroarginine Methyl Ester
  • Animals
  • Calcium (pharmacology)
  • Calmodulin (pharmacology)
  • Enzyme Inhibitors (pharmacology)
  • Female
  • Long-Term Potentiation (drug effects, physiology)
  • Male
  • NG-Nitroarginine Methyl Ester (pharmacology)
  • Nitric Oxide (physiology)
  • Nitric Oxide Synthase (antagonists & inhibitors)
  • Pyramidal Cells (drug effects, physiology)
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction (drug effects, physiology)
  • Synapses (drug effects, physiology)

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