Role of GABA receptors in nitric oxide inhibition of dorsolateral periaqueductal gray neurons.
Nitric oxide (NO) affects neuronal activity of the midbrain periaqueductal gray (PAG). The purpose of this report was to investigate the role of GABA receptors in NO modulation of neuronal activity through inhibitory and excitatory synaptic inputs within the dorsolateral PAG (dl-PAG). First, spontaneous miniature inhibitory postsynaptic currents (mIPSCs) and excitatory postsynaptic currents (mEPSCs) were recorded using whole cell voltage-clamp methods. Increased NO by either S-nitroso-N-acetyl-penicillamine (SNAP, 100 microM) or L-arginine (50 microM) significantly augmented the frequency of mIPSCs of the dl-PAG neurons without altering their amplitudes or decay time constants. The effects were eliminated after bath application of carboxy-PTIO (NO scavenger), and 1-(2-trifluorom-ethylphenyl) imidazole (NO synthase inhibitor). In contrast, SNAP and L-arginine did not alter mEPSCs in dl-PAG neurons. However the frequency of mEPSCs was significantly increased with prior application of the GABA(B) receptors antagonist, CGP55845. In addition, NO significantly decreased the discharge rate of spontaneous action potentials in the dl-PAG neurons and the effect was reduced in the presence of the GABA(A) receptor antagonist, bicuculline. Our data show that within the dl-PAG NO potentiates the synaptic release of GABA, while NO-induced GABA presynaptically inhibits glutamate release through GABA(B) receptors. Overall, NO suppresses neuronal activity of the dl-PAG via a potentiation of GABAergic synaptic inputs and via GABA(A) receptors.
Xing
Jihong
J
Heart and Vascular Institute and Department of Medicine, The Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey, PA 17033, USA.
Li
De-Pei
DP
Li
Jianhua
J
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D000818:Animals; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology; D018682:GABA Agents / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D010487:Periaqueductal Gray / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000502:physiology*
D003497:Cyclic N-Oxides; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D016166:Free Radical Scavengers; D018682:GABA Agents; D007093:Imidazoles; D020030:Nitric Oxide Donors; D018079:Receptors, GABA; C110881:S-nitro-N-acetylpenicillamine; C079391:2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide; D009569:Nitric Oxide; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D010396:Penicillamine