title: Sodium influx pathways during and after anoxia in rat hippocampal neurons.
abstract: Mechanisms that contribute to Na+ influx during and immediately after 5 min anoxia were investigated in cultured rat hippocampal neurons loaded with the Na+-sensitive fluorophore sodium-binding benzofuran isophthalate. During anoxia, an influx of Na+ in the face of reduced Na+,K+-ATPase activity caused a rise in [Na+]i. After the return to normoxia, Na+,K+-ATPase activity mediated the recovery of [Na+]i despite continued Na+ entry. Sodium influx during and after anoxia occurred through multiple pathways and increased the longer neurons were maintained in culture. Under the experimental conditions used, Na+ entry during anoxia did not reflect the activation of ionotropic glutamate receptors, TTX- or lidocaine-sensitive Na+ channels, plasmalemmal Na+/Ca2+ exchange, Na+/H+ exchange, or HCO3--dependent mechanisms; rather, contributions were received from a Gd3+-sensitive pathway activated by reactive oxygen species and Na+/K+/2Cl- cotransport in neurons maintained for 6-10 and 11-14 d in vitro (DIV), respectively. Sodium entry immediately after anoxia was not attributable to the activation of ionotropic glutamate receptors, voltage-activated Na+ channels, or Na+/K+/2Cl- cotransport; rather, it occurred via Na+/Ca2+ exchange, Na+/H+ exchange, and a Gd3+-sensitive pathway similar to that observed during anoxia; 11-14 DIV neurons received an additional contribution from an -dependent mechanism(s). The results provide insight into the intrinsic mechanisms that contribute to disturbed internal Na+ homeostasis during and immediately after anoxia in rat hippocampal neurons and, in this way, may play a role in the pathogenesis of anoxic or ischemic cell injury.
authors.affiliation: Department of Physiology, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3.
authors.forename: Claire
authors.initials: C
authors.lastname: Sheldon
authors.forename: Abdoullah
authors.initials: A
authors.lastname: Diarra
authors.forename: Y May
authors.initials: YM
authors.lastname: Cheng
authors.forename: John
authors.initials: J
authors.lastname: Church
mesh_terms: D000818:Animals; D001639:Bicarbonates; D001693:Biological Transport, Active / Q000502:physiology; D002478:Cells, Cultured; D004594:Electrophysiology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D002534:Hypoxia, Brain / Q000378:metabolism*; D007473:Ion Channels / Q000502:physiology; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017470:Receptors, Glutamate / Q000502:physiology; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology; D019831:Sodium-Calcium Exchanger / Q000502:physiology; D017923:Sodium-Hydrogen Exchangers / Q000502:physiology; D028021:Sodium-Potassium-Chloride Symporters / Q000502:physiology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013997:Time Factors
chemical_list: D001639:Bicarbonates; D007473:Ion Channels; D017470:Receptors, Glutamate; D015222:Sodium Channels; D019831:Sodium-Calcium Exchanger; D017923:Sodium-Hydrogen Exchangers; D028021:Sodium-Potassium-Chloride Symporters; C491711:nonselective cation channel protein, rat; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase