PMID- 18585443 OWN - NLM STAT- MEDLINE DCOM- 20081203 LR - 20131121 IS - 0306-4522 (Print) IS - 0306-4522 (Linking) VI - 155 IP - 2 DP - 2008 Aug 13 TI - Nitric oxide modulates the firing rate of the rat supraoptic magnocellular neurons. PG - 359-65 LID - 10.1016/j.neuroscience.2008.06.005 [doi] AB - 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. FAU - Ventura, R R AU - Ventura RR AD - Department of Physiology, School of Medicine of Ribeirao Preto, University of Sao Paulo, Av. Bandeirantes, 3900, 14049-900 Ribeirao Preto, Sao Paulo, Brazil. FAU - Aguiar, J F AU - Aguiar JF FAU - Antunes-Rodrigues, J AU - Antunes-Rodrigues J FAU - Varanda, W A AU - Varanda WA LA - eng PT - Journal Article DEP - 20080608 PL - United States TA - Neuroscience JT - Neuroscience JID - 7605074 RN - 31C4KY9ESH (Nitric Oxide) RN - 94ZLA3W45F (Arginine) RN - V55S2QJN2X (NG-Nitroarginine Methyl Ester) SB - IM MH - Action Potentials/drug effects/*physiology MH - Animals MH - Arginine/pharmacology MH - Female MH - Male MH - Membrane Potentials/drug effects/physiology MH - NG-Nitroarginine Methyl Ester/pharmacology MH - Neurons/drug effects/*physiology MH - Nitric Oxide/*physiology MH - Organ Culture Techniques MH - Patch-Clamp Techniques MH - Rats MH - Rats, Inbred WF MH - Supraoptic Nucleus/cytology/drug effects/*physiology EDAT- 2008/07/01 09:00 MHDA- 2008/12/17 09:00 CRDT- 2008/07/01 09:00 PHST- 2008/04/14 00:00 [received] PHST- 2008/06/02 00:00 [revised] PHST- 2008/06/02 00:00 [accepted] PHST- 2008/07/01 09:00 [pubmed] PHST- 2008/12/17 09:00 [medline] PHST- 2008/07/01 09:00 [entrez] AID - S0306-4522(08)00880-4 [pii] AID - 10.1016/j.neuroscience.2008.06.005 [doi] PST - ppublish SO - Neuroscience. 2008 Aug 13;155(2):359-65. doi: 10.1016/j.neuroscience.2008.06.005. Epub 2008 Jun 8.