Ischemia opens neuronal gap junction hemichannels.
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.
Thompson
Roger J
RJ
Department of Psychiatry and Brain Research Centre, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada.
Zhou
Ning
N
MacVicar
Brian A
BA
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology*; D002229:Carbenoxolone / Q000494:pharmacology; D015687:Cell Hypoxia; D002463:Cell Membrane Permeability; D017630:Connexins; D005452:Fluoresceins / Q000378:metabolism; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology*; D005947:Glucose / Q000172:deficiency / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D007811:Lanthanum / Q000494:pharmacology; D008564:Membrane Potentials; D051379:Mice; D009336:Necrosis; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009474:Neurons / Q000473:pathology / Q000502:physiology* / Q000648:ultrastructure; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D012235:Rhodamines / Q000378:metabolism; D020521:Stroke / Q000473:pathology / Q000503:physiopathology
D017630:Connexins; D005452:Fluoresceins; D007473:Ion Channels; D009419:Nerve Tissue Proteins; D012235:Rhodamines; C083098:calcein green; C479936:pannexin 1, rat; C028521:lanthanum chloride; D007811:Lanthanum; D000255:Adenosine Triphosphate; C050829:sulforhodamine 101; D005947:Glucose; D002229:Carbenoxolone