PMID- 27807172
OWN - NLM
STAT- MEDLINE
DCOM- 20170719
LR  - 20200225
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 36
IP  - 44
DP  - 2016 Nov 2
TI  - Nitric Oxide Modulates HCN Channels in Magnocellular Neurons of the Supraoptic 
      Nucleus of Rats by an S-Nitrosylation-Dependent Mechanism.
PG  - 11320-11330
AB  - The control of the excitability in magnocellular neurosecretory cells (MNCs) of 
      the supraoptic nucleus has been attributed mainly to synaptic inputs from 
      circunventricular organs. However, nitric oxide (NO), a gaseous messenger 
      produced in this nucleus during isotonic and short-term hypertonic conditions, is 
      an example of a modulator that can act directly on MNCs to modulate their firing 
      rate. NO inhibits the electrical excitability of MNCs, leading to a decrease in 
      the release of vasopressin and oxytocin. Although the effects of NO on MNCs are 
      well established, the mechanism by which this gas produces its effect is, so far, 
      unknown. Because NO acts independently of synaptic inputs, we hypothesized that 
      ion channels present in MNCs are the targets of NO. To investigate this 
      hypothesis, we used the patch-clamp technique in vitro and in situ to measure 
      currents carried by hyperpolarization-activated and nucleotide-gated cation (HCN) 
      channels and establish their role in determining the electrical excitability of 
      MNCs in rats. Our results show that blockade of HCN channels by ZD7288 decreases 
      MNC firing rate with significant consequences on the release of OT and VP, 
      measured by radioimmunoassay. NO induced a significant reduction in HCN currents 
      by binding to cysteine residues and forming S-nitrosothiol complexes. These 
      findings shed new light on the mechanisms that control the electrical 
      excitability of MNCs via the nitrergic system and strengthen the importance of 
      HCN channels in the control of hydroelectrolyte homeostasis. SIGNIFICANCE 
      STATEMENT: Cells in our organism live in a liquid environment whose composition 
      and osmolality are maintained within tight limits. Magnocellular neurons (MNCs) 
      of the supra optic nucleus can sense osmolality and control the synthesis and 
      secretion of vasopressin (VP) and oxytocin (OT) by the neurohypophysis. OT and VP 
      act on the kidneys controlling the excretion of water and sodium to maintain 
      homeostasis. Here we combined electrophysiology, molecular biology, and 
      radioimmunoassay to show that the electrical activity of MNCs can be controlled 
      by nitric oxide (NO), a gaseous messenger. NO reacts with cysteine residues 
      (S-nitrosylation) on hyperpolarization-activated and nucleotide-gated cation 
      channels decreasing the firing rate of MNCs and the consequent secretion of VP 
      and OT.
CI  - Copyright (c) 2016 the authors 0270-6474/16/3611320-11$15.00/0.
FAU - Pires da Silva, Melina
AU  - Pires da Silva M
AUID- ORCID: 0000-0001-5730-0993
AD  - Department of Physiology, Ribeirao Preto Medical School, University of Sao Paulo, 
      14049-900 Ribeirao Preto, Sao Paulo, Brazil, and melina@rfi.fmrp.usp.br.
FAU - de Almeida Moraes, Davi Jose
AU  - de Almeida Moraes DJ
AD  - Department of Physiology, Ribeirao Preto Medical School, University of Sao Paulo, 
      14049-900 Ribeirao Preto, Sao Paulo, Brazil, and.
FAU - Mecawi, Andre de Souza
AU  - Mecawi AS
AD  - Department of Physiological Sciences, Biology Institute, Federal Rural University 
      of Rio de Janeiro, 23890-000, Seropedica, Rio de Janeiro, Brazil.
FAU - Rodrigues, Jose Antunes
AU  - Rodrigues JA
AD  - Department of Physiology, Ribeirao Preto Medical School, University of Sao Paulo, 
      14049-900 Ribeirao Preto, Sao Paulo, Brazil, and.
FAU - Varanda, Wamberto Antonio
AU  - Varanda WA
AUID- ORCID: 0000-0003-3473-3299
AD  - Department of Physiology, Ribeirao Preto Medical School, University of Sao Paulo, 
      14049-900 Ribeirao Preto, Sao Paulo, Brazil, and.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels)
RN  - 31C4KY9ESH (Nitric Oxide)
SB  - IM
MH  - Action Potentials/*physiology
MH  - Animals
MH  - Cells, Cultured
MH  - Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels/*metabolism
MH  - Ion Channel Gating/*physiology
MH  - Male
MH  - Neuroendocrine Cells/*physiology
MH  - Nitric Oxide/*metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Supraoptic Nucleus/*physiology
PMC - PMC6601964
OTO - NOTNLM
OT  - HCN channels
OT  - S-nitrosylation
OT  - electrolyte homeostasis
OT  - electrophysiology
OT  - magnocellular neurons
OT  - nitric oxide
EDAT- 2016/11/04 06:00
MHDA- 2017/07/20 06:00
PMCR- 2017/05/02
CRDT- 2016/11/04 06:00
PHST- 2016/05/15 00:00 [received]
PHST- 2016/09/14 00:00 [accepted]
PHST- 2016/11/04 06:00 [pubmed]
PHST- 2017/07/20 06:00 [medline]
PHST- 2016/11/04 06:00 [entrez]
PHST- 2017/05/02 00:00 [pmc-release]
AID - 36/44/11320 [pii]
AID - 1588-16 [pii]
AID - 10.1523/JNEUROSCI.1588-16.2016 [doi]
PST - ppublish
SO  - J Neurosci. 2016 Nov 2;36(44):11320-11330. doi: 10.1523/JNEUROSCI.1588-16.2016.