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Neuronal excitotoxicity during stroke is caused by activationof unidentified large-conductance channels, leading to swellingand calcium dysregulation. We show that ischemic-like conditions[O2/glucose deprivation (OGD)] open hemichannels, or half gapjunctions, in neurons. Hemichannel opening was indicated bya large linear current and flux across the membrane of smallfluorescent molecules. Single-channel openings of hemichannels(530 picosiemens) were observed in OGD. Both the current anddye flux were blocked by inhibitors of hemichannels. Therefore,hemichannel opening contributes to the profound ionic dysregulationduring stroke and may be a ubiquitous component of ischemicneuronal death.
Department of Psychiatry and Brain Research Centre, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada.
* To whom correspondence should be addressed. E-mail: bmacvica{at}interchange.ubc.ca
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Both sides now: multiple interactions of ATP with pannexin-1 hemichannels. Focus on "A permeant regulating its permeation pore: inhibition of pannexin 1 channels by ATP".
G. R. Dubyak (2009)
Am J Physiol Cell Physiol
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Activation of Pannexin-1 Hemichannels Augments Aberrant Bursting in the Hippocampus.
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Science
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Neuroprotection by Cell Permeable TAT-mGluR1 Peptide in Ischemia: Synergy between Carrier and Cargo Sequences.
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Neuroscientist
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Divalent Cations Regulate Connexin Hemichannels by Modulating Intrinsic Voltage-dependent Gating.
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Damage-Induced Activation of ERK1/2 in Cochlear Supporting Cells Is a Hair Cell Death-Promoting Signal That Depends on Extracellular ATP and Calcium.
Two-Photon Imaging of Stroke Onset In Vivo Reveals That NMDA-Receptor Independent Ischemic Depolarization Is the Major Cause of Rapid Reversible Damage to Dendrites and Spines.
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Pannexin 1 and pannexin 3 are glycoproteins that exhibit many distinct characteristics from the connexin family of gap junction proteins.
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Hemichannels in cardiomyocytes open transiently during ischemia and contribute to reperfusion injury following brief ischemia.
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Gap junctions on hippocampal mossy fiber axons demonstrated by thin-section electron microscopy and freeze fracture replica immunogold labeling.
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