The nitric oxide--cyclic GMP pathway and synaptic depression in rat hippocampal slices.
The ability of exogenous nitric oxide (NO) to modify synaptic transmission was investigated in area CA1 of the rat hippocampal slice. The NO donors S-nitroso-N-acetylpenicillamine (SNAP) and S-nitrosoglutathione (SNOG) depressed field excitatory postsynaptic potentials evoked by low frequency stimulation of the Schaffer collateral-commissural pathway. Upon washout of the NO donors, synaptic transmission rapidly returned to control levels. A similar reversible synaptic depression was produced by SNAP when tetanic stimulation (100 Hz; 1 s) was delivered in its presence. The effect of SNAP was not mimicked by its precursor or breakdown product and was blocked by haemoglobin, indicating that the effect involved NO. Roussin's black salt, a photolabile NO donor, also depressed transiently field excitatory postsynaptic potentials following photolysis. The depression was induced rapidly following a flash of UV light (20 s duration) focused onto the slice using a confocal microscope. The depressant effect of the NO donors on synaptic transmission was mimicked by zaprinast, a specific cGMP-phosphodiesterase inhibitor. Zaprinast depressed to a similar extent both the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate and N-methyl-D-aspartate receptor-mediated components of excitatory postsynaptic currents without affecting passive membrane properties, indicating a presynaptic locus of action. SNAP, SNOG and zaprinast all elevated cGMP levels in rat hippocampal slices. Immunocytochemical staining revealed that the cGMP accumulation was mainly in a network of varicose fibres running throughout the CA1 region, consistent with a presynaptic site of action of NO. We conclude that NO, possibly through activation of guanylate cyclase, may be involved in transient presynaptic depression in the CA1 region of the hippocampus.
Physiological Laboratory, University of Liverpool, UK.
C L
CL
Boulton
A J
AJ
Irving
E
E
Southam
B
B
Potier
J
J
Garthwaite
G L
GL
Collingridge
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000818:Animals; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects; D005260:Female; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism; D006624:Hippocampus / Q000502:physiology*; D007120:Immunochemistry; D066298:In Vitro Techniques; D009569:Nitric Oxide / Q000502:physiology*; D009603:Nitroso Compounds / Q000378:metabolism; D010396:Penicillamine / Q000031:analogs & derivatives / Q000378:metabolism; D010782:Photolysis; D011688:Purinones / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D026423:S-Nitroso-N-Acetylpenicillamine; D026422:S-Nitrosoglutathione; D009435:Synaptic Transmission / Q000502:physiology*
D009603:Nitroso Compounds; D011688:Purinones; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; D026423:S-Nitroso-N-Acetylpenicillamine; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D005978:Glutathione; D010396:Penicillamine; C011145:zaprinast; D006152:Cyclic GMP