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Nitric oxide inhibits spinally projecting paraventricular neurons through potentiation of presynaptic GABA release.
- Source :
-
Journal of neurophysiology [J Neurophysiol] 2002 Nov; Vol. 88 (5), pp. 2664-74. - Publication Year :
- 2002
-
Abstract
- Nitric oxide (NO) in the paraventricular nucleus (PVN) is involved in the regulation of the excitability of PVN neurons. However, the effect of NO on the inhibitory GABAergic and excitatory glutamatergic inputs to spinally projecting PVN neurons has not been studied specifically. In the present study, we determined the role of the inhibitory GABAergic and excitatory glutamatergic inputs in the inhibitory action of NO on spinally projecting PVN neurons. Spinally projecting PVN neurons were retrogradely labeled by a fluorescent dye, 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocasbocyane (DiI), injected into the spinal cord of rats. Whole cell voltage- and current-clamp recordings were performed on DiI-labeled PVN neurons in the hypothalamic slice. The spontaneous miniature inhibitory postsynaptic currents (mIPSCs) recorded in DiI-labeled neurons were abolished by 20 microM bicuculline, whereas the miniature excitatory postsynaptic currents (mEPSCs) were eliminated by 20 microM 6-cyano-7-nitroquinoxaline-2,3-dione. Bath application of an NO donor, 100 microM S-nitroso-N-acetyl-penicillamine (SNAP), or the NO precursor, 100 microM L-arginine, both significantly increased the frequency of mIPSCs of DiI-labeled PVN neurons, without altering the amplitude and the decay time constant of mIPSCs. The effect of SNAP and L-arginine on the frequency of mIPSCs was eliminated by an NO scavenger, 2-(4-carboxypheny)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, and an NO synthase inhibitor, 1-(2-trifluoromethylphenyl) imidazole, respectively. Neither SNAP nor L-arginine significantly altered the frequency and the amplitude of mEPSCs. Under current-clamp conditions, 100 microM SNAP or 100 microM L-arginine significantly decreased the discharge rate of the DiI-labeled PVN neurons, without significantly affecting the resting membrane potential. On the other hand, 20 microM bicuculline significantly increased the impulse activity of PVN neurons. In the presence of bicuculline, SNAP or L-arginine both failed to inhibit the firing activity of PVN neurons. This electrophysiological study provides substantial new evidence that NO suppresses the activity of spinally projecting PVN neurons through potentiation of the GABAergic synaptic input.
- Subjects :
- Action Potentials drug effects
Action Potentials physiology
Animals
Arginine pharmacology
Bicuculline pharmacology
Electrophysiology
GABA Antagonists pharmacology
Immunohistochemistry
In Vitro Techniques
Membrane Potentials physiology
Microscopy, Confocal
Neural Pathways cytology
Neural Pathways drug effects
Neural Pathways physiology
Nitric Oxide Donors pharmacology
Nitric Oxide Synthase antagonists & inhibitors
Nitric Oxide Synthase metabolism
Nitric Oxide Synthase physiology
Nitric Oxide Synthase Type I
Paraventricular Hypothalamic Nucleus drug effects
Patch-Clamp Techniques
Rats
Rats, Sprague-Dawley
Receptors, Presynaptic drug effects
Spinal Cord drug effects
Neurons drug effects
Nitric Oxide pharmacology
Paraventricular Hypothalamic Nucleus cytology
Receptors, Presynaptic metabolism
Spinal Cord cytology
gamma-Aminobutyric Acid metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0022-3077
- Volume :
- 88
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of neurophysiology
- Publication Type :
- Academic Journal
- Accession number :
- 12424302
- Full Text :
- https://doi.org/10.1152/jn.00540.2002