NO inhibits supraoptic oxytocin and vasopressin neurons via activation of GABAergic synaptic inputs.
To study modulatory actions of nitric oxide (NO) on GABAergic synaptic activity in hypothalamic magnocellular neurons in the supraoptic nucleus (SON), in vitro and in vivo electrophysiological recordings were obtained from identified oxytocin and vasopressin neurons. Whole cell patch-clamp recordings were obtained in vitro from immunochemically identified oxytocin and vasopressin neurons. GABAergic synaptic activity was assessed in vitro by measuring GABA(A) miniature inhibitory postsynaptic currents (mIPSCs). The NO donor and precursor sodium nitroprusside (SNP) and L-arginine, respectively, increased the frequency and amplitude of GABA(A) mIPSCs in both cell types (P < or = 0.001). Retrodialysis of SNP (50 mM) onto the SON in vivo inhibited the activity of both neuronal types (P < or = 0.002), an effect that was reduced by retrodialysis of the GABA(A)-receptor antagonist bicuculline (2 mM, P < or = 0.001). Neurons activated by intravenous infusion of 2 M NaCl were still strongly inhibited by SNP. These results suggest that NO inhibition of neuronal excitability in oxytocin and vasopressin neurons involves pre- and postsynaptic potentiation of GABAergic synaptic activity in the SON.
Stern
J E
JE
Department of Pharmacology and Toxicology, Wright State University, Dayton, Ohio 45435, USA. javier.stern@wright.edu
Ludwig
M
M
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D004553:Electric Conductivity; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D066298:In Vitro Techniques; D009433:Neural Inhibition / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010121:Oxytocin / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000502:physiology; D013495:Supraoptic Nucleus / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D014667:Vasopressins / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D020030:Nitric Oxide Donors; D011963:Receptors, GABA-A; D014667:Vasopressins; D009599:Nitroprusside; D009569:Nitric Oxide; D010121:Oxytocin; D005680:gamma-Aminobutyric Acid; D001120:Arginine; D001640:Bicuculline