Hypoxia-induced modification of the [formula omitted] receptor in the brain of the newborn piglet

Abstract

The effect of hypoxia on the N- methyl- d-aspartate (NMDA) receptor/ion channel complex in the brain cell membrane of the newborn piglet was studied. Experiments were conducted on newborn piglets, 2–4 days of age, that were anesthetized and mechanically ventilated. Hypoxic hypoxia was induced in the experimental group by lowering the F iO 2 to 5–7%. The control group was ventilated under normoxic conditions. Tissue hypoxia was documented biochemically by decreased levels of ATP and phosphocreatine (PCr) in the hypoxic group (52% and 81% lower than the normoxic group, respectively). [ 3H]MK-801 binding characteristics ( B max = number of receptors, K d = dissociation constant) were used as an index of NMDA receptor modification. In hypoxic brains, B max decreased from the control level of 1.13 ± 0.15 pmol/mg protein to 0.68 ± 0.23 pmol/mg protein ( P < 0.01) and the K d value decreased (reflecting increased affinity) from 9.46 ± 1.68 nM in the control brains to 4.87 ± 1.42 nM ( P < 0.01) in the hypoxic brains. The Na +,K +-ATPase activity, an index of brain cell membrane function, decreased from a control value of 46.5 ± 0.4 to 40.5 ± 2.3 μmol inorganic phosphate (Pi)/mg protein/h ( P < 0.005) during hypoxia. The results of this study indicate that hypoxia in newborn piglets modifies the NMDA receptor in the cerebral cortex, resulting in an increased affinity of the receptor channel. Hypoxia-induced modification of the NMDA ion/receptor complex may be a potential mechanism of cerebral excitotoxicity.