Increased expression of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in reactive astrocytes following ischemia
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
25042871
DOI
10.1002/glia.22721
Knihovny.cz E-zdroje
- Klíčová slova
- HCN channels, ZD7288, astrocytes, cortex, focal and global cerebral ischemia, hippocampus,
- MeSH
- AMP cyklický farmakologie MeSH
- astrocyty účinky léků metabolismus MeSH
- gliový fibrilární kyselý protein genetika metabolismus MeSH
- ischemie patologie MeSH
- kationtové kanály řízené cyklickými nukleotidy genetika metabolismus MeSH
- krysa rodu Rattus MeSH
- membránové potenciály účinky léků fyziologie MeSH
- modely nemocí na zvířatech MeSH
- mozek cytologie MeSH
- myši transgenní MeSH
- myši MeSH
- neurony účinky léků metabolismus MeSH
- potkani Wistar MeSH
- proteiny nervové tkáně genetika metabolismus MeSH
- pyrimidiny farmakologie MeSH
- regulace genové exprese účinky léků fyziologie MeSH
- sodík metabolismus MeSH
- techniky in vitro MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- AMP cyklický MeSH
- gliový fibrilární kyselý protein MeSH
- ICI D2788 MeSH Prohlížeč
- kationtové kanály řízené cyklickými nukleotidy MeSH
- proteiny nervové tkáně MeSH
- pyrimidiny MeSH
- sodík MeSH
Astrocytes respond to ischemic brain injury by proliferation, the increased expression of intermediate filaments and hypertrophy, which results in glial scar formation. In addition, they alter the expression of ion channels, receptors and transporters that maintain ionic/neurotransmitter homeostasis. Here, we aimed to demonstrate the expression of Hcn1-4 genes encoding hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in reactive astrocytes following focal cerebral ischemia (FCI) or global cerebral ischemia (GCI) and to characterize their functional properties. A permanent occlusion of the middle cerebral artery (MCAo) was employed to induce FCI in adult GFAP/EGFP mice, while GCI was induced by transient bilateral common carotid artery occlusion combined with hypoxia in adult rats. Using FACS, we isolated astrocytes from non-injured or ischemic brains and performed gene expression profiling using single-cell RT-qPCR. We showed that 2 weeks after ischemia reactive astrocytes express high levels of Hcn1-4 transcripts, while immunohistochemical analyses confirmed the presence of HCN1-3 channels in reactive astrocytes 5 weeks after ischemia. Electrophysiological recordings revealed that post-ischemic astrocytes are significantly depolarized, and compared with astrocytes from non-injured brains, they display large hyperpolarization-activated inward currents, the density of which increased 2-3-fold in response to ischemia. Their activation was facilitated by cAMP and their amplitudes were decreased by ZD7288 or low extracellular Na(+) concentration, suggesting that they may belong to the family of HCN channels. Collectively, our results demonstrate that regardless of the type of ischemic injury, reactive astrocytes express HCN channels, which could therefore be an important therapeutic target in poststroke therapy.
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