Premium
Role for nitric oxide in permeability of hippocampal neuronal hemichannels during oxygen glucose deprivation
Author(s) -
Zhang Le,
Deng Tongle,
Sun Yiguo,
Liu Kezhou,
Yang Yi,
Zheng Xiaoxiang
Publication year - 2008
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21675
Subject(s) - soluble guanylyl cyclase , nitric oxide , chemistry , calcein , biophysics , intracellular , depolarization , biochemistry , microbiology and biotechnology , s nitrosylation , pannexin , pharmacology , biology , connexin , gap junction , enzyme , cysteine , membrane , organic chemistry , guanylate cyclase
Increased hemichannel opening induced by oxygen glucose deprivation (OGD) was reported in the hippocampal pyramidal neuron. It was suggested that the pannexin1 hemichannel opening could mediate ionic flux dysregulation, anoxic depolarization, and energy‐depleting efflux of glucose and ATP for ischemic neurons. However, the regulatory mechanisms of pannexin1 hemichannel opening have been poorly understood. Here we showed that excessive generation of nitric oxide (NO) during ischemia could induce the calcein leakage from neurons, which was markedly reduced by NO synthase inhibitor. The calcein leakage from neurons during OGD was also attenuated by the application of N‐ethylmaleimide (NEM), an SH‐alkylating agent, and dithiothreitol (DTT), a reducer of oxidized sulfhydryl groups. However, the soluble guanylyl cyclase (sGC) inhibitor had a minor effect on the calcein leakage during OGD. Furthermore, the elevated intracellular but not extracellular levels of glutathione could also inhibit the calcein leakage during OGD. Similar results were observed in metabolic inhibition (MI), which is another ischemic‐like condition. Finally, immunocytochemical and immunoblotting analysis revealed that, after 1 hr of OGD stimulation, the distribution and expression of pannexin1 showed no significant difference compared with control. However, the pannexin1 mRNA expression was elevated after 1 hr of OGD and a sustained increase was maintained during reperfusion. These results implied that the reactive oxygen species (ROS), especially NO, might be involved in the enhanced pannexin1 hemichannel opening and that the S‐nitrosylation but not the NO/cGMP pathway played a more important role in this event. © 2008 Wiley‐Liss, Inc.