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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
Caenorhabditis elegans Innexins Regulate Active Zone Differentiation.
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|Abstract »|Full Text »|PDF »
Loop Gating of Connexin Hemichannels Involves Movement of Pore-lining Residues in the First Extracellular Loop Domain.
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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
296, C235-C241
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Activation of Pannexin-1 Hemichannels Augments Aberrant Bursting in the Hippocampus.
R. J. Thompson, M. F. Jackson, M. E. Olah, R. L. Rungta, D. J. Hines, M. A. Beazely, J. F. MacDonald, and B. A. MacVicar (2008)
Science
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Neuroprotection by Cell Permeable TAT-mGluR1 Peptide in Ischemia: Synergy between Carrier and Cargo Sequences.
Wei Xu, Miou Zhou, and M. Baudry (2008)
Neuroscientist
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|Abstract »|PDF »
Divalent Cations Regulate Connexin Hemichannels by Modulating Intrinsic Voltage-dependent Gating.
Connexin Hemichannel Composition Determines the FGF-1-induced Membrane Permeability and Free [Ca2+]i Responses.
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Mol. Biol. Cell
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|Abstract »|Full Text »|PDF »
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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A Central Role of Connexin 43 in Hypoxic Preconditioning.
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Gap Junctions Are Required for NMDA Receptor Dependent Cell Death in Developing Neurons.
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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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Am J Physiol Heart Circ Physiol
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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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PNAS
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Am J Physiol Cell Physiol
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H+ Ion Activation and Inactivation of the Ventricular Gap Junction: A Basis for Spatial Regulation of Intracellular pH.
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