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.
Ko
G Y
GY
Department of Neurobiology and Anatomy, University of Texas Medical School at Houston, Houston, Texas 77225, USA.
Kelly
P T
PT
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002147:Calmodulin / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology
D002147:Calmodulin; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester