title: Hypoxia and neuronal function under in vitro conditions.
abstract: Neurons in the mammalian CNS are highly sensitive to the availability of oxygen. Hypoxia can alter neuronal function and can lead to neuronal injury or death. The underlying changes in the membrane properties of single neurons have been studied in vitro in slice preparations obtained from various brain areas. Hypoxic changes of membrane potential and input resistance correspond to a decrease in ATP concentration and an increase in internal Ca2+ concentration. Functional modifications consisting of substantial membrane depolarization and failure of synaptic transmission can be observed within a few minutes following onset of hypoxia. The hypoxic depolarization accompanied by a hyperexcitability is a trigger signal for induction of neuronal cell death and is mediated mainly by activation of glutamate receptors. The mechanisms of the hypoxic hyperpolarization are more complex. Two types of potassium channels contribute to the hyperpolarization, the Ca(2+)- and the ATP-activated potassium channel. A number of neurotransmitters and neuromodulators is involved in the preservation of normal cell function during hypoxia. Therefore, hypoxia-induced cellular changes are unlikely to have a single, discrete pathway. The complexity of cellular changes implies that several strategies may be useful for neuroprotection and a successful intervention may be dependent upon drug action at more than one target site.
authors.affiliation: Institut für Pharmazie, Universität Lehrstuhl Pharmakologie für Natur Wissenschaftler, Leipzig, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Nieber
mesh_terms: D002118:Calcium / Q000378:metabolism; D015687:Cell Hypoxia / Q000502:physiology*; D048429:Cell Size; D066298:In Vitro Techniques; D007473:Ion Channels / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology*; D008954:Models, Biological; D009474:Neurons / Q000502:physiology*; D011687:Purines / Q000737:chemistry; D009435:Synaptic Transmission
chemical_list: D007473:Ion Channels; D011687:Purines; D002118:Calcium