title: Nitric oxide modulates the firing rate of the rat supraoptic magnocellular neurons.
abstract: In vitro, nitric oxide (NO) inhibits the firing rate of magnocellular neurosecretory cells (MNCs) of hypothalamic supraoptic and paraventricular nuclei and this effect has been attributed to GABAergic activation. However, little is known about the direct effects of NO in MNCs. We used the patch-clamp technique to verify the effect of L-arginine, a precursor for NO synthesis, and N(omega)-nitro-L-arginine methyl ester hydrochloride (L-NAME), an inhibitor of NOS, on spontaneous electrical activity of MNCs after glutamatergic and GABAergic blockade in Wistar rat brain slices. 6-Cyano-7-nitroquinoxaline-2,3-dione (CNQX) (10 microM) and dl-2-amino-5-phosphonovaleric acid (dl-AP5) (30 microM) were used to block postsynaptic glutamatergic currents, and picrotoxin (30 microM) and saclofen (30 microM) to block ionotropic and metabotropic postsynaptic GABAergic currents. Under these conditions, 500 microM L-arginine decreased the firing rate from 3.7+/-0.6 Hz to 1.3+/-0.3 Hz. Conversely, 100 microM L-NAME increased the firing rate from 3.0+/-0.3 Hz to 5.8+/-0.4 Hz. All points histogram analysis showed changes in resting potential from -58.1+/-0.8 mV to -62.2+/-1.1 mV in the presence of L-arginine and from -59.8+/-0.7 mV to -56.9+/-0.8 mV by L-NAME. Despite the nitrergic modulator effect on firing rate, some MNCs had no significant changes in their resting potential. In those neurons, hyperpolarizing after-potential (HAP) amplitude increased from 12.4+/-1.2 mV to 16.8+/-0.7 mV by L-arginine, but without significant changes by L-NAME treatment. To our knowledge, this is the first demonstration that NO can inhibit MNCs independent of GABAergic inputs. Further, our results point to HAP as a potential site for nitrergic modulation.
authors.affiliation: Department of Physiology, School of Medicine of Ribeirão Preto, University of São Paulo, Av. Bandeirantes, 3900, 14049-900 Ribeirão Preto, São Paulo, Brazil.
authors.forename: R R
authors.initials: RR
authors.lastname: Ventura
authors.forename: J F
authors.initials: JF
authors.lastname: Aguiar
authors.forename: J
authors.initials: J
authors.lastname: Antunes-Rodrigues
authors.forename: W A
authors.initials: WA
authors.lastname: Varanda
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D005260:Female; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D051381:Rats; D011920:Rats, Inbred WF; D013495:Supraoptic Nucleus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
chemical_list: D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester