Abstract
Neuronal excitotoxicity during stroke is caused by activation of unidentified large-conductance channels, leading to swelling and calcium dysregulation. We show that ischemic-like conditions [O(2)/glucose deprivation (OGD)] open hemichannels, or half gap junctions, in neurons. Hemichannel opening was indicated by a large linear current and flux across the membrane of small fluorescent molecules. Single-channel openings of hemichannels (530 picosiemens) were observed in OGD. Both the current and dye flux were blocked by inhibitors of hemichannels. Therefore, hemichannel opening contributes to the profound ionic dysregulation during stroke and may be a ubiquitous component of ischemic neuronal death.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine Triphosphate / metabolism
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Animals
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Brain Ischemia / pathology
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Brain Ischemia / physiopathology*
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Carbenoxolone / pharmacology
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Cell Hypoxia
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Cell Membrane Permeability
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Connexins
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Fluoresceins / metabolism
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Gap Junctions / drug effects
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Gap Junctions / physiology*
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Glucose / deficiency
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Glucose / metabolism
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Hippocampus / cytology
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In Vitro Techniques
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Ion Channels / drug effects
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Ion Channels / physiology*
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Lanthanum / pharmacology
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Membrane Potentials
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Mice
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Necrosis
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Nerve Tissue Proteins / physiology*
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Neurons / pathology
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Neurons / physiology*
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Neurons / ultrastructure
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Patch-Clamp Techniques
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Rats
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Rats, Wistar
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Rhodamines / metabolism
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Stroke / pathology
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Stroke / physiopathology
Substances
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Connexins
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Fluoresceins
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Ion Channels
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Nerve Tissue Proteins
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Rhodamines
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calcein green
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pannexin 1, rat
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lanthanum chloride
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Lanthanum
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Adenosine Triphosphate
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sulforhodamine 101
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Glucose
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Carbenoxolone