Nitric Oxide Modulates HCN Channels in Magnocellular Neurons of the Supraoptic Nucleus of Rats by an S-Nitrosylation-Dependent Mechanism

Autor(es)

da Silva, Melina Pires ; de Almeida Moraes, Davi Jose ; Mecawi, Andre de Souza ; Rodrigues, Jose Antunes ; Varanda, Wamberto Antonio

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF NEUROSCIENCE; v. 36, n. 44, p. 11320-11330, NOV 2 2016.
• Citações Web of Science: 4

Resumo

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. (AU)

• Processo FAPESP: 12/19750-7 - Óxido nítrico como modulador da atividade elétrica de neurônios magnocelulares do núcleo supraóptico do rato
• Beneficiário: Wamberto Antonio Varanda
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/10484-5 - Caracterização eletrofisiológica e molecular dos neurônios envolvidos na geração do ritmo e do padrão respiratório de ratos durante o desenvolvimento pós-natal
• Beneficiário: Davi José de Almeida Moraes
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores