title: Adaptations of vertebrate neurons to hypoxia and anoxia: maintaining critical Ca2+ concentrations.
abstract: Down-regulation of ion channel activity ('channel arrest'), which aids in preserving critical ion gradients in concert with greatly diminished energy production, is one important strategy by which anoxia-tolerant neurons adapt to O2 shortage. Channel arrest results in the elimination of action potentials and neurotransmission and also decreases the need for ion transport, which normally requires a large energy expenditure. Important targets of this down-regulation may be channels in which activity would otherwise result in the toxic increases in intracellular [Ca2+] characteristic of anoxia-sensitive mammalian neurons. In turtles, Na+ channels and the Ca2+-permeable ion channel of the N-methyl-d-aspartate (NMDA)-type glutamate receptor undergo down-regulation during anoxia. Inactivation of NMDA receptors during hypoxia occurs by a variety of mechanisms, including alterations in the phosphorylation state of ion channel subunits, Ca2+-dependent second messenger activation, changes in Ca2+-dependent polymerization/depolymerization of actin to postsynaptic receptors and activation of other G-protein-coupled receptors. Release of inhibitory neurotransmitters (e.g. gamma-aminobutyrate) and neuromodulators (e.g. adenosine) into the brain extracellular fluids may play an important role in the down-regulation of these and other types of ion channels.
authors.affiliation: Medical Sciences 261, Department of Anesthesia, University of California at San Francisco, CA 94143-0542, USA. phil_bickler@quickmail.ucsf.edu
authors.forename: P E
authors.initials: PE
authors.lastname: Bickler
authors.forename: L T
authors.initials: LT
authors.lastname: Buck
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000502:physiology*; D015687:Cell Hypoxia / Q000502:physiology; D009474:Neurons / Q000378:metabolism* / Q000502:physiology*; D014714:Vertebrates / Q000502:physiology*
chemical_list: D002118:Calcium